TY - GEN A1 - Teuschl, Andreas A1 - Fuchs, Christiane T1 - Bioreactors in Musculoskeletal Tissue Engineering KW - Bioreactor KW - Tissue Engineering Y1 - ER - TY - JOUR A1 - Maleiner, Babette A1 - Tomasch, Janine A1 - Heher, Philipp A1 - Spadiut, Oliver A1 - Rünzler, Dominik A1 - Fuchs, Christiane T1 - The Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models. JF - Frontiers in Physiology N2 - Classical approaches to engineer skeletal muscle tissue based on current regenerative and surgical procedures still do not meet the desired outcome for patient applications. Besides the evident need to create functional skeletal muscle tissue for the repair of volumetric muscle defects, there is also growing demand for platforms to study muscle-related diseases, such as muscular dystrophies or sarcopenia. Currently, numerous studies exist that have employed a variety of biomaterials, cell types and strategies for maturation of skeletal muscle tissue in 2D and 3D environments. However, researchers are just at the beginning of understanding the impact of different culture settings and their biochemical (growth factors and chemical changes) and biophysical cues (mechanical properties) on myogenesis. With this review we intend to emphasize the need for new in vitro skeletal muscle (disease) models to better recapitulate important structural and functional aspects of muscle development. We highlight the importance of choosing appropriate system components, e.g., cell and biomaterial type, structural and mechanical matrix properties or culture format, and how understanding their interplay will enable researchers to create optimized platforms to investigate myogenesis in healthy and diseased tissue. Thus, we aim to deliver guidelines for experimental designs to allow estimation of the potential influence of the selected skeletal muscle tissue engineering setup on the myogenic outcome prior to their implementation. Moreover, we offer a workflow to facilitate identifying and selecting different analytical tools to demonstrate the successful creation of functional skeletal muscle tissue. Ultimately, a refinement of existing strategies will lead to further progression in understanding important aspects of muscle diseases, muscle aging and muscle regeneration to improve quality of life of patients and enable the establishment of new treatment options. KW - Bioreactor KW - Muscle KW - Biomaterial Y1 - ER - TY - JOUR A1 - Tomasch, Janine A1 - Maleiner, Babette A1 - Heher, Philipp A1 - Rufin, Manuel A1 - Andriotis, Orestis G. A1 - Thurner, Philipp J. A1 - Redl, Heinz A1 - Fuchs, Christiane A1 - Teuschl-Woller, Andreas H. T1 - Changes in Elastic Moduli of Fibrin Hydrogels Within the Myogenic Range Alter Behavior of Murine C2C12 and Human C25 Myoblasts Differently JF - Froniers in Bioengineering and Biotechnology N2 - Fibrin hydrogels have proven highly suitable scaffold materials for skeletal muscle tissue engineering in the past. Certain parameters of those types of scaffolds, however, greatly affect cellular mechanobiology and therefore the myogenic outcome. The aim of this study was to identify the influence of apparent elastic properties of fibrin scaffolds in 2D and 3D on myoblasts and evaluate if those effects differ between murine and human cells. Therefore, myoblasts were cultured on fibrin-coated multiwell plates (“2D”) or embedded in fibrin hydrogels (“3D”) with different elastic moduli. Firstly, we established an almost linear correlation between hydrogels’ fibrinogen concentrations and apparent elastic moduli in the range of 7.5 mg/ml to 30 mg/ml fibrinogen (corresponds to a range of 7.7–30.9 kPa). The effects of fibrin hydrogel elastic modulus on myoblast proliferation changed depending on culture type (2D vs 3D) with an inhibitory effect at higher fibrinogen concentrations in 3D gels and vice versa in 2D. The opposite effect was evident in differentiating myoblasts as shown by gene expression analysis of myogenesis marker genes and altered myotube morphology. Furthermore, culture in a 3D environment slowed down proliferation compared to 2D, with a significantly more pronounced effect on human myoblasts. Differentiation potential was also substantially impaired upon incorporation into 3D gels in human, but not in murine, myoblasts. With this study, we gained further insight in the influence of apparent elastic modulus and culture type on cellular behavior and myogenic outcome of skeletal muscle tissue engineering approaches. Furthermore, the results highlight the need to adapt parameters of 3D culture setups established for murine cells when applied to human cells. KW - Tissue Engineering KW - Fibrin KW - Hydrogel KW - Biomaterials KW - Cell Culture Y1 - VL - 10 SP - 836520 ER - TY - JOUR A1 - Angelova, Liliya A1 - Daskalova, Albena A1 - Filipov, Emil A1 - Monforte Vila, Xavier A1 - Tomasch, Janine A1 - Avdeev, Georgi A1 - Teuschl-Woller, Andreas Herbert A1 - Buchvarov, Ivan T1 - Optimizing the Surface Structural and Morphological Properties of Silk Thin Films via Ultra-Short Laser Texturing for Creation of Muscle Cell Matrix Model JF - Polymers N2 - Temporary scaffolds that mimic the extracellular matrix's structure and provide a stable substratum for the natural growth of cells are an innovative trend in the field of tissue engineering. The aim of this study is to obtain and design porous 2D fibroin-based cell matrices by femtosecond laser-induced microstructuring for future applications in muscle tissue engineering. Ultra-fast laser treatment is a non-contact method, which generates controlled porosity-the creation of micro/nanostructures on the surface of the biopolymer that can strongly affect cell behavior, while the control over its surface characteristics has the potential of directing the growth of future muscle tissue in the desired direction. The laser structured 2D thin film matrices from silk were characterized by means of SEM, EDX, AFM, FTIR, Micro-Raman, XRD, and 3D-roughness analyses. A WCA evaluation and initial experiments with murine C2C12 myoblasts cells were also performed. The results show that by varying the laser parameters, a different structuring degree can be achieved through the initial lifting and ejection of the material around the area of laser interaction to generate porous channels with varying widths and depths. The proper optimization of the applied laser parameters can significantly improve the bioactive properties of the investigated 2D model of a muscle cell matrix. Keywords: biopolymers; femtosecond laser processing; muscle cell matrix 2D model; muscle tissue engineering; silk fibroin. KW - Tissue Engineering KW - Muscle Cell matrix Model KW - Silk Scaffold KW - Surface Structure Y1 - VL - 2022 IS - 14(13), 2584 ER - TY - GEN A1 - Heher, Philipp A1 - Tomasch, Janine A1 - Maleiner, Babette A1 - Redl, Heinz A1 - Fuchs, Christiane T1 - The Importance of Biomechanical Cues for In Vitro Skeletal Myogenesis KW - In Vitro KW - Myogenesis Y1 - 2018 ER - TY - GEN A1 - Tomasch, Janine T1 - Generation of 3D skeletal muscle-like scaffolds via the application of mechanical stimuli KW - Scaffold KW - Mechanical Stimuli Y1 - 2018 ER - TY - JOUR A1 - Schuh, Christina A1 - Heher, Philipp A1 - Weihs, Anna A1 - Fuchs, Christiane A1 - Gabriel, Christian A1 - Wolbank, Susanne A1 - Mittermayr, Rainer A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Teuschl, Andreas T1 - In vitro extracorporeal shock wave treatment enhances stemness and preserves multipotency of rat and human adipose-derived stem cells JF - Journal of Cytotherapy KW - Shockwave Y1 - ER - TY - CHAP A1 - Köhler, Gottfried A1 - Rünzler, Dominik A1 - Mayer, B. A1 - Sára, Margit A1 - Rasmussen, S. A1 - Buravkova, L. T1 - Microgravity. Applications in Biotechnology and Bioorganic Materials Sciences T2 - 10 Years Space biomedical Research and Development in Austria KW - Microgravity KW - Biotechnology KW - Materials Sciences Y1 - 2019 SP - 65 EP - 85 PB - Facultas CY - Wien ER - TY - JOUR A1 - Purtscher, Michaela A1 - Rothbauer, Mario A1 - Kratz, Sebastian Rudi Adam A1 - Bailey, Andrew A1 - Lieberzeit, Peter A1 - Ertl, Peter T1 - A microfluidic impedance-based extended infectivity assay: combining retroviral amplification and cytopathic effect monitoring on a single lab-on-a-chip platform JF - Lab on a Chip N2 - Detection, quantification and monitoring of virus – host cell interactions are of great importance when evaluating the safety of pharmaceutical products. With the wide usage of viral based vector systems in combination with mammalian cell lines for the production of biopharmaceuticals, the presence of replication competent viral particles needs to be avoided and potential hazards carefully assessed. Consequently, regulatory agencies recommend viral clearance studies using plaque assays or TCID50 assays to evaluate the efficiency of the production process in removing viruses. While plaque assays provide reliable information on the presence of viral contaminations, they are still tedious to perform and can take up to two weeks to finish. To overcome some of these limitations, we have automated, miniaturized and integrated the dual cell culture bioassay into a common lab-on-a-chip platform containing embedded electrical sensor arrays to enrich and detect infectious viruses. Results of our microfluidic single step assay show that a significant reduction in assay time down to 3 to 4 days can be achieved using simultaneous cell-based viral amplification, release and detection of cytopathic effects in a target cell line. We further demonstrate the enhancing effect of continuous fluid flow on infection of PG-4 reporter cells by newly formed and highly active virions by M. dunni cells, thus pointing to the importance of physical relevant viral–cell interactions. KW - Tissue Engineering KW - Microfluidics KW - Lab on Chip Y1 - 2021 VL - 2021 IS - Issue 7 SP - 1364 EP - 1372 ER - TY - JOUR A1 - Zupkovitz, Gordin A1 - Kabiljo, Julijan A1 - Kothmayer, Michael A1 - Schlick, Katharina A1 - Schöfer, Christian A1 - Lagger, Sabine A1 - Pusch, Oliver T1 - Analysis of Methylation Dynamics Reveals a Tissue-Specific, Age-Dependent Decline in 5-Methylcytosine Within the Genome of the Vertebrate Aging Model Nothobranchius furzeri. JF - Frontiers in Molecular Biosciences N2 - Erosion of the epigenetic DNA methylation landscape is a widely recognized hallmark of aging. Emerging advances in high throughput sequencing techniques, in particular DNA methylation data analysis, have resulted in the establishment of precise human and murine age prediction tools. In vertebrates, methylation of cytosine at the C5 position of CpG dinucleotides is executed by DNA methyltransferases (DNMTs) whereas the process of enzymatic demethylation is highly dependent on the activity of the ten-eleven translocation methylcytosine dioxygenase (TET) family of enzymes. Here, we report the identification of the key players constituting the DNA methylation machinery in the short-lived teleost aging model Nothobranchius furzeri. We present a comprehensive spatio-temporal expression profile of the methylation-associated enzymes from embryogenesis into late adulthood, thereby covering the complete killifish life cycle. Data mining of the N. furzeri genome produced five dnmt gene family orthologues corresponding to the mammalian DNMTs (DNMT1, 2, 3A, and 3B). Comparable to other teleost species, N. furzeri harbors multiple genomic copies of the de novo DNA methylation subfamily. A related search for the DNMT1 recruitment factor UHRF1 and TET family members resulted in the identification of N. furzeri uhrf1, tet1, tet2, and tet3. Phylogenetic analysis revealed high cross-species similarity on the amino acid level of all individual dnmts, tets, and uhrf1, emphasizing a high degree of functional conservation. During early killifish development all analyzed dnmts and tets showed a similar expression profile characterized by a strong increase in transcript levels after fertilization, peaking either at embryonic day 6 or at the black eye stage of embryonic development. In adult N. furzeri, DNA methylation regulating enzymes showed a ubiquitous tissue distribution. Specifically, we observed an age-dependent downregulation of dnmts, and to some extent uhrf1, which correlated with a significant decrease in global DNA methylation levels in the aging killifish liver and muscle. The age-dependent DNA methylation profile and spatio-temporal expression characteristics of its enzymatic machinery reported here may serve as an essential platform for the identification of an epigenetic aging clock in the new vertebrate model system N. furzeri. KW - Tissue Engineering KW - Killifish KW - Aging Model Y1 - VL - 8 IS - 627143 ER - TY - CHAP A1 - Wießner, Katharina A1 - Machacek-Link, Thomas A1 - Leitner, Rita T1 - Encouraging the development of higher-order cognitive skills via applied exercises and web-based self-assessment to teach the basic principles in molecular biology. T2 - PIXEL NPSE2021, März 2021 N2 - The responsibility of a lecturer is not only to share his or her knowledge with the students in an easy to understand manner, but also to help the students to embed new knowledge and to encourage the development of higher-order cognitive skills via applied exercises. In order to meet the growing demand for blended learning approaches a new course concept was established in autumn 2018. To enhance comprehension and to provide opportunities for self-assessment, web-based training units were implemented by using the interactive learning software “Articulate Storyline”. Students had to prepare at home for the course units by completing interactive chapters. Their learning outcome was assessed by online quizzes at the end of each chapter. Online Training chapters allowed time to focus on selected topics and to repeat key messages in following presence units. Additionally, guided group exercises were performed to promote analytic skills and abstract thinking. The students had to apply and combine their knowledge to solve problem-based challenges. An optional revision course was offered to the students, which allowed for interactive repetition of the acquired knowledge with the focus on student-to-lecturer dialog. An analysis based on a written evaluation of this course resulted in a positive feedback from the students, in particular regarding the guided exercises and the offered revision course. According to the students the group exercises allowed to process the learned subjects, promoted the group climate and were a convenient diversion from the frontal lecture format. Students who attended the revision course on a regular basis showed a better performance at the final exam and exceeded especially at interdisciplinary questions. The first implementation of this master´s degree course indicated that the combination of web-based training elements with frontal lecture elements, guided exercises stimulating cognitive skills and an optional revision course can teach students the basics of biology in an understandable way. This course structure is especially applicable to teach basic subjects for groups of students with varying initial knowledge. Financial support from the City of Vienna project PBL in Molecular Life Science (21-06) is gratefully acknowledged. KW - PBL KW - Didaktik KW - Lehre Y1 - ER - TY - JOUR A1 - Deininger, Christian A1 - Wagner, Andrea A1 - Heimel, Patrick A1 - Salzer, Elias A1 - Monforte Vila, Xavier A1 - Weißenbacher, Nadja A1 - Grillari, Johannes A1 - Redl, Heinz A1 - Wichlas, Florian A1 - Freude, Thomas A1 - Tempfer, Herbert A1 - Teuschl-Woller, Andreas A1 - Traweger, Andreas T1 - Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite JF - Int. J. Mol. Sci. N2 - The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing. KW - Tissue Engineering KW - Biomaterials KW - silk scaffold KW - bone regeneration KW - pseudoarthrosis Y1 - VL - 23 IS - 1 / 283 ER - TY - JOUR A1 - Hackethal, Johannes A1 - Dungel, Peter A1 - Teuschl, Andreas Herbert T1 - Frequently Used Strategies to Isolate Extracellular Matrix Proteins from Human Placenta and Adipose Tissue JF - Tissue Engineering Part C: Methods N2 - The natural extracellular matrix (ECM) provides the optimal environment for cells. Many enzymatic or non-enzymatic based strategies to extract ECM proteins from tissues were published over the past years. However, every single isolation strategy reported so far is associated with specific bottlenecks. In this study, frequently used strategies to isolate ECM from human placenta or adipose tissue using Tris-, serum-, or pepsin-based buffers were compared. The resulting ECM proteins were biochemically characterized by analysis of cellular remnants using Hoechst DNA staining, glycosaminoglycan (GAG) content by dimethylmethylene blue, visualization of protein bands using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis combined with amino acid quantification, and assessment of the proangiogenic profile using an angiogenesis array. Tris-NaCl-extracted ECM proteins showed a high heterogenic degree of extracted proteins, bioactive growth factors, and GAGs, but no collagen-I. Active serum-extracted ECM showed significant lower DNA remnants when compared with the Tris-NaCl isolation strategy. Pepsin-extracted ECM was rich in collagen-I and low amounts of remaining bioactive growth factors. This strategy was most effective to reduce DNA amounts when compared with the other isolation strategies. Pepsin-extracted ECM from both tissues easily gelled at 37°C, whereas the other extracted ECM strategies did not gel at 37°C (Tris-NaCl: liquid; serum: sponge). All relevant characteristics (DNA residues, ECM diversity and bioactivity, shape) of the extracted ECM proteins highly depend on its isolation strategy and could still be optimized. Impact statement The natural human extracellular matrix (ECM) is the ideal cell niche. Various strategies were reported to isolate human ECM components from various sources. In this article, we compared frequently used methods and compared their characteristics (DNA remnants, glycosaminoglycan content, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, amino acid quantification, angiogenesis array, and gel formation). We conclude that more research is still necessary to optimize current isolation approaches for in vitro or in vivo applications of human ECM. KW - Tissue Engineering KW - Biomaterials KW - Adipose Tissue KW - extracellular matrix KW - human placenta Y1 - VL - 27 IS - 12 SP - 649 EP - 660 ER - TY - JOUR A1 - Khimich, Margarita A. A1 - Prosolov, Konstantin A. A1 - Mishurova, Tatiana A1 - Evsevleev, Sergej A1 - Monforte, Xavier A1 - Teuschl, Andreas H. A1 - Slezak, Paul A1 - Ibragimov, Egor A. A1 - Saprykin, Alexander A. A1 - Kovalevskaya, Zhanna G. A1 - Dmitriev, Andrey I. A1 - Bruno, Giovanni A1 - Sharkeev, Yurii P. T1 - Advances in Laser Additive Manufacturing of Ti-Nb Alloys: From Nanostructured Powders to Bulk Objects JF - Nanomaterials (Basel) N2 - The additive manufacturing of low elastic modulus alloys that have a certain level of porosity for biomedical needs is a growing area of research. Here, we show the results of manufacturing of porous and dense samples by a laser powder bed fusion (LPBF) of Ti-Nb alloy, using two distinctive fusion strategies. The nanostructured Ti-Nb alloy powders were produced by mechanical alloying and have a nanostructured state with nanosized grains up to 90 nm. The manufactured porous samples have pronounced open porosity and advanced roughness, contrary to dense samples with a relatively smooth surface profile. The structure of both types of samples after LPBF is formed by uniaxial grains having micro- and nanosized features. The inner structure of the porous samples is comprised of an open interconnected system of pores. The volume fraction of isolated porosity is 2 vol. % and the total porosity is 20 vol. %. Cell viability was assessed in vitro for 3 and 7 days using the MG63 cell line. With longer culture periods, cells showed an increased cell density over the entire surface of a porous Ti-Nb sample. Both types of samples are not cytotoxic and could be used for further in vivo studies. KW - Tissue Engineering KW - Biomaterials KW - Laser Additive Manufacturing KW - Bulk Objects Y1 - VL - 11 IS - 5 / 1159 ER - TY - JOUR A1 - Farokhi, Maryam A1 - Aleemardani, Mina A1 - Solouk, Atefeh A1 - Mirzadeh, Hamid A1 - Teuschl, Andreas Herbert A1 - Redl, Heinz T1 - Crosslinking strategies for silk fibroin hydrogels: promising biomedical materials JF - Biomedical Materials N2 - Due to their strong biomimetic potential, silk fibroin (SF) hydrogels are impressive candidates for tissue engineering, due to their tunable mechanical properties, biocompatibility, low immunotoxicity, controllable biodegradability, and a remarkable capacity for biomaterial modification and the realization of a specific molecular structure. The fundamental chemical and physical structure of SF allows its structure to be altered using various crosslinking strategies. The established crosslinking methods enable the formation of three-dimensional (3D) networks under physiological conditions. There are different chemical and physical crosslinking mechanisms available for the generation of SF hydrogels (SFHs). These methods, either chemical or physical, change the structure of SF and improve its mechanical stability, although each method has its advantages and disadvantages. While chemical crosslinking agents guarantee the mechanical strength of SFH through the generation of covalent bonds, they could cause some toxicity, and their usage is not compatible with a cell-friendly technology. On the other hand, physical crosslinking approaches have been implemented in the absence of chemical solvents by the induction of β-sheet conformation in the SF structure. Unfortunately, it is not easy to control the shape and properties of SFHs when using this method. The current review discusses the different crosslinking mechanisms of SFH in detail, in order to support the development of engineered SFHs for biomedical applications. KW - Tissue Engineering KW - hydrogels KW - Biomaterials KW - silk fibroin Y1 - VL - 16 IS - 2 SP - 022004 ER - TY - JOUR A1 - Schanda, Jakob A1 - Keibl, Claudia A1 - Heimel, Patrick A1 - Monforte, Xavier A1 - Feichtinger, Xaver A1 - Teuschl, Andreas A1 - Baierl, Andreas A1 - Muschitz, Christian A1 - Redl, Heinz A1 - Fialka, Christian A1 - Mittermayr, Rainer T1 - Zoledronic Acid Substantially Improves Bone Microarchitecture and Biomechanical Properties After Rotator Cuff Repair in a Rodent Chronic Defect Model JF - Am J Sports Med N2 - Background: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. Hypothesis: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. Study design: Controlled laboratory study. Methods: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. Results: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. Conclusion: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. Clinical relevance: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations. KW - Tissue Engineering KW - Rotator Cuff Tears Y1 - VL - 2020 Jul IS - 48 (9) SP - 2151 EP - 2160 ER - TY - JOUR A1 - Bachmann, Barbara A1 - Spitz, Sarah A1 - Schädl, Barbara A1 - Teuschl, Andreas A1 - Redl, Heinz A1 - Nürnberger, Sylvia A1 - Ertl, Peter T1 - Stiffness Matters: Fine-Tuned Hydrogel Elasticity Alters Chondrogenic Redifferentiation JF - Froniers in Bioengineering and Biotechnology N2 - Biomechanical cues such as shear stress, stretching, compression, and matrix elasticity are vital in the establishment of next generation physiological in vitro tissue models. Matrix elasticity, for instance, is known to guide stem cell differentiation, influence healing processes and modulate extracellular matrix (ECM) deposition needed for tissue development and maintenance. To better understand the biomechanical effect of matrix elasticity on the formation of articular cartilage analogs in vitro, this study aims at assessing the redifferentiation capacity of primary human chondrocytes in three different hydrogel matrices of predefined matrix elasticities. The hydrogel elasticities were chosen to represent a broad spectrum of tissue stiffness ranging from very soft tissues with a Young's modulus of 1 kPa up to elasticities of 30 kPa, representative of the perichondral-space. In addition, the interplay of matrix elasticity and transforming growth factor beta-3 (TGF-β3) on the redifferentiation of primary human articular chondrocytes was studied by analyzing both qualitative (viability, morphology, histology) and quantitative (RT-qPCR, sGAG, DNA) parameters, crucial to the chondrotypic phenotype. Results show that fibrin hydrogels of 30 kPa Young's modulus best guide chondrocyte redifferentiation resulting in a native-like morphology as well as induces the synthesis of physiologic ECM constituents such as glycosaminoglycans (sGAG) and collagen type II. This comprehensive study sheds light onto the mechanobiological impact of matrix elasticity on formation and maintenance of articular cartilage and thus represents a major step toward meeting the need for advanced in vitro tissue models to study both re- and degeneration of articular cartilage. KW - Tissue Engineering KW - Chondrogenic Redifferentiation KW - Biomaterials Y1 - 2021 VL - 2020 IS - 8 SP - 373 ER - TY - JOUR A1 - Simböck, Elisabeth A1 - Marksteiner, Jessica A1 - Machacek, Thomas A1 - Wiessner, Katharina A1 - Gepp, Barbara A1 - Jesenberger, Veronika A1 - Weihs, Anna A1 - Leitner, Rita T1 - The Power of Problem Based Learning beyond its Didactic Attributes JF - Journal of Problem Based Learning in Higher Education (JPBLHE) N2 - Hybrid courses with a focus on practice-orientated education and self-guided learning phases are on the rise on the higher education sector. Disciplines in Life Sciences implicate a high degree of practical laboratory expertise. The University of Applied Sciences (UAS) in Vienna, Austria, has thus been endeavoured offering students a high qualitative education integrating hybrid courses based on PBL principles, which consist of on-site (including the transmission of necessary background and practical laboratory training) and off-site (including self-study phases) sessions. As practical laboratory units are central in those courses, the restrictive measures, including the transition to a complete online teaching format due to the first Covid-19-pandemic lock-down, had severe effects on the implementation and the quality of the curriculum. According to surveys made specifically to address this problematic situation, it can be concluded that on-site practical units are fundamental for certain disciplines such as Life Sciences. KW - Problem-based Learning KW - Life Science didactics KW - Hybrid PBL-methods KW - COVID-19 KW - Life Science Education Y1 - VL - 9 IS - 1 SP - 109 EP - 130 ER - TY - CHAP A1 - Wießner, Katharina A1 - Praher, Daniela A1 - Liousia, Varvara A1 - Gepp, Barbara A1 - Leitner, Rita A1 - Rünzler, Dominik T1 - Testing the acute toxicity of an alternative to Glyphosate - Pelargonic acid T2 - SETAC Europe 30th Annual Meeting - Online N2 - Glyphosate-based herbicides were used as plant protection product globally for several decades. However, glyphosate is discussed as showing genotoxicity and many other side-effects such as inhibiting the mitochondrial succinate dehydrogenase, leading to a decreased ATP production. Therefore, finding alternative active substances is necessary. Pelargonic acid (nonanoic acid) and its ammonium salt (saponified form), which are used as alternatives to glyphosate-based herbicides, are biological derived substances considered as environmentally friendly herbicides. To test the effects of pelargonic acid in its acidic form (active substance in TopGun) and its saponified form (in Finalsan Plus) on the aquatic ecosystem, students of the master study program “environmental management and ecotoxicology” compared the toxicity levels of these substances using zebrafish embryos within the scope of a student research course. The project was developed by applying the 7-step problem-based learning method which allowed the students to design their experiments independently with the guidance and feedback of the lecturers. Acute toxicity was determined according to OECD test guideline 236 in D. rerio which revealed a LC50 of 1.55 mg/L of pelargonic acid, a LC50 value of 0.93 mg/L pelargonic acid in TopGun and a LC50 of 36.37 mg/L of Finalsan Plus. Neutral Red Uptake assays were performed on the rainbow trout-derived gill cell-line RTgill-W1 to determine the acute toxicity according to the OECD test guideline 129 which revealed the IC50 value of 12.4 mg/L pelargonic acid in TG. Due to solubility limits, no reliable IC50 could be obtained. The results of the tests indicate differences in the acute toxicity of the pelargonic acid-based formulations TopGun and Finalsan Plus. However, more investigations have to be done in order to analyse if the acidic form is more toxic than the saponified form. Furthermore, detailed ecotoxicological risk assessments and an evaluation of the genotoxicity of both herbicides has to be performed before any conclusion can be drawn. Financial support from the City of Vienna project PBL in Molecular Life Science (21-06) is gratefully acknowledged. KW - Environmental Chemistry KW - Ecotoxicology Y1 - 2020 ER - TY - JOUR A1 - Ziadlou, Reihane A1 - Rotman, Stijn A1 - Teuschl, Andreas A1 - Salzer, Elias A1 - Barbero, Andrea A1 - Martin, Ivan A1 - Alini, Mauro A1 - Eglin, David A1 - Grad, Sibylle T1 - Optimization of hyaluronic acid-tyramine/silk-fibroin composite hydrogels for cartilage tissue engineering and delivery of anti-inflammatory and anabolic drugs JF - Materials Science and Engineering: C N2 - Injury of articular cartilage leads to an imbalance in tissue homeostasis, and due to the poor self-healing capacity of cartilage the affected tissue often exhibits osteoarthritic changes. In recent years, injectable and highly tunable composite hydrogels for cartilage tissue engineering and drug delivery have been introduced as a desirable alternative to invasive treatments. In this study, we aimed to formulate injectable hydrogels for drug delivery and cartilage tissue engineering by combining different concentrations of hyaluronic acid-tyramine (HA-Tyr) with regenerated silk-fibroin (SF) solutions. Upon enzymatic crosslinking, the gelation and mechanical properties were characterized over time. To evaluate the effect of the hydrogel compositions and properties on extracellular matrix (ECM) deposition, bovine chondrocytes were embedded in enzymatically crosslinked HA-Tyr/SF composites (in further work abbreviated as HA/SF) or HA-Tyr hydrogels. We demonstrated that all hydrogel formulations were cytocompatible and could promote the expression of cartilage matrix proteins allowing chondrocytes to produce ECM, while the most prominent chondrogenic effects were observed in hydrogels with HA20/SF80 polymeric ratios. Unconfined mechanical testing showed that the compressive modulus for HA20/SF80 chondrocyte-laden constructs was increased almost 10-fold over 28 days of culture in chondrogenic medium which confirmed the superior production of ECM in this hydrogel compared to other hydrogels in this study. Furthermore, in hydrogels loaded with anabolic and anti-inflammatory drugs, HA20/SF80 hydrogel showed the longest and the most sustained release profile over time which is desirable for the long treatment duration typically necessary for osteoarthritic joints. In conclusion, HA20/SF80 hydrogel was successfully established as a suitable injectable biomaterial for cartilage tissue engineering and drug delivery applications. KW - Tissue Engineering KW - Cartilage KW - Mechanical Testing KW - Biomaterials KW - Chondrocytes Y1 - VL - 120 IS - 111701 ER - TY - JOUR A1 - Quartinello, Felice A1 - Tallian, Claudia A1 - Auer, Julia A1 - Schön, Herta A1 - Vielnascher, Robert A1 - Weinberger, Simone A1 - Wieland, Karin A1 - Weihs, Anna A1 - Rollett, Alexandra A1 - Lendl, Bernhard A1 - Teuschl, Andreas A1 - Pellis, Alessandro A1 - Gübitz, Georg T1 - Smart Textiles in Wound Care: Functionalization of Cotton/PET Blends with Antimicrobial Nanocapsules JF - Journal of Materials Chemistry B KW - Smart textiles KW - Tissue Engineering KW - Regenerative Medicine KW - Antimicrobial KW - Wound Y1 - 2019 ER - TY - JOUR A1 - Feichtinger, Xaver A1 - Monforte, Xavier A1 - Keibl, Claudia A1 - Hercher, David A1 - Schanda, Jakob A1 - Teuschl, Andreas A1 - Muschitz, Christian A1 - Redl, Heinz A1 - Fialka, Christian A1 - Mittermayr, Rainer T1 - Substantial Biomechanical Improvement by Extracorporeal Shockwave Therapy After Surgical Repair of Rodent Chronic Rotator Cuff Tears. JF - American Journal of Sports Medicine KW - Shockwave Therapy KW - Tissue Engineering KW - Regeneration KW - Surgery Y1 - ER - TY - JOUR A1 - Teuschl, Andreas A1 - Tangl, Stefan A1 - Heimel, Patrick A1 - Schwarze, Uwe Yacine A1 - Monforte, Xavier A1 - Redl, Heinz A1 - Nau, Thomas T1 - Osteointegration of a Novel Silk Fiber-Based ACL Scaffold by Formation of a Ligament-Bone Interface. JF - American Journal of Sports Medicine KW - Tissue Engineering KW - Silk KW - Scaffold KW - ACL Y1 - ER - TY - JOUR A1 - Simsa, Robin A1 - Monforte, Xavier A1 - Salzer, Elias A1 - Teuschl, Andreas A1 - Jenndahl, Lachmi A1 - Bergh, Niklas A1 - Fogelstrand, Per T1 - Effect of fluid dynamics on decellularization efficacy and mechanical properties of blood vessels. JF - PLoS One KW - Tissue Engineering KW - Decellularization KW - Blood Vessel Y1 - ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Zmajkovicova, Katarina A1 - Catalanotti, Federica A1 - Baumgartner, Christian A1 - Reyes, Gloria Ximena A1 - Baccarini, Manuela T1 - MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance JF - Mol. Cell N2 - The Raf/MEK/ERK and PI3K/Akt pathways are prominent effectors of oncogenic Ras. These pathways negatively regulate each other, but the mechanism involved is incompletely understood. We now identify MEK1 as an essential regulator of lipid/protein phosphatase PTEN, through which it controls phosphatidylinositol-3-phosphate accumulation and AKT signaling. MEK1 ablation stabilizes AKT activation and, in vivo, causes a lupus-like autoimmune disease and myeloproliferation. Mechanistically, MEK1 is necessary for PTEN membrane recruitment as part of a ternary complex containing the multidomain adaptor MAGI1. Complex formation is independent of MEK1 kinase activity but requires phosphorylation of T292 on MEK1 by activated ERK. Thus, inhibiting the ERK pathway reduces PTEN membrane recruitment, increasing phosphatidylinositol-3-phosphate accumulation and AKT activation. Our data offer a conceptual framework for the observation that activation of the PI3K pathway frequently mediate resistance to MEK inhibitors and for the promising results obtained by combined MEK/PI3K inhibition in preclinical cancer models. KW - MEK1 pathway KW - membrane recruitment KW - preclinical cancer models Y1 - 2020 VL - 2013 IS - 50 SP - 43 EP - 55 ER - TY - CHAP A1 - Nebel, Sabrina A1 - Salado Manzano, Cristina A1 - Just, Valentin A1 - Leeb, Christine A1 - Jesenberger, Veronika T1 - Role of the MEK/ERK pathway in chondrogenic differentiation: Establishment of a protocol for the generation of MEK1-knockout hTERT ASCs and assessment of their differentiation potential T2 - Proceedings des Forschungsforum 2017 der österreichischen Fachhochschulen KW - Chondrogenesis Y1 - 2018 ER - TY - GEN A1 - Nebel, Sabrina A1 - Salado Manzano, Cristina A1 - Just, Valentin A1 - Leeb, Christine A1 - Jesenberger, Veronika T1 - Role of the MEK/ERK pathway in chondrogenic differentiation: Establishment of a protocol for the generation of MEK1-knockout hTERT ASCs and assessment of their differentiation potential KW - Chondrogenesis Y1 - 2018 ER - TY - CHAP A1 - Leitner, Rita A1 - Gepp, Barbara A1 - Liousia, Varvara A1 - Rünzler, Dominik T1 - Teaching 3R principles in ecotoxicology by performing a problem-based learning project T2 - ALTEX Proceedings, LINZ 2018 – EUSAAT 2018, Volume 7, No. 2, ISSN 2194-0479 (2018) KW - Problem Based Learning KW - Teaching KW - Ecotoxicology KW - 3R Principles Y1 - ER - TY - JOUR A1 - Catalanotti, Federica A1 - Reyes, Gloria Ximena A1 - Jesenberger, Veronika A1 - Galabova-Kovacs, Gergana A1 - de Matos Simoes, Ricardo A1 - Carugo, Oliviero A1 - Baccarini, Manuela T1 - A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal JF - Nat Struct Mol Biol. N2 - Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling. Here we describe a previously uncharacterized, unexpected role of Mek1 in downregulating Mek2-dependent Erk signaling. Mek1 mediates the regulation of Mek2 in the context of a previously undiscovered Mek1-Mek2 complex. The Mek heterodimer is negatively regulated by Erk-mediated phosphorylation of Mek1 on Thr292, a residue missing in Mek2. Disabling this Erk-proximal negative-feedback step stabilizes the phosphorylation of both Mek2 and Erk in cultured cells and in vivo in Mek1 knockout embryos and mice. Thus, in disagreement with the current perception of the pathway, the role of Mek1 and Mek2 in growth factor-induced Erk phosphorylation is not interchangeable. Our data establish Mek1 as the crucial modulator of Mek and Erk signaling and have potential implications for the role of Mek1 and Mek2 in tumorigenesis. KW - Mek1-Mek2 pathway KW - tumorigenesis KW - ERK activation KW - cancer biology Y1 - 2020 VL - 2009 IS - 16(3) SP - 294 EP - 303 ER - TY - GEN A1 - Leitner, Rita T1 - PBL-Szenario mit degressivem Support durch Lehrende im Modul "Angewandtes Forschungsprojekt in Umweltmanagement" KW - Problem Based Learning KW - Didactics KW - Environmental Management Y1 - ER - TY - GEN A1 - Gepp, Barbara A1 - Liousia, Varvara A1 - Machacek, Thomas A1 - Praher, Daniela A1 - Eisner, Katharina A1 - Limbeck, Sophie A1 - Gamper, Janine A1 - Schwarzl, Elisabeth A1 - Hazod, Till A1 - Landwehr, Renate A1 - Wenger, Charlotte A1 - Olscher, Christoph A1 - Leitner, Rita A1 - Rünzler, Dominik T1 - Pelargonic acid - an alternative to glyphosate-based herbicides? KW - Ecotoxicology KW - Herbicides Y1 - ER - TY - GEN A1 - Leitner, Rita T1 - Teaching 3R principles in ecotoxicology by performing a problem-based learning project KW - Problem Based Learning KW - Teaching KW - Ecotoxicology KW - Education KW - 3R Principles Y1 - ER - TY - GEN A1 - Küenburg, Bernhard A1 - Teuschl, Andreas T1 - Regenerative silk ligament: scale up and regulatory strategy of a textile engineered silk implant for tissue regeneration of injured human ACL (anterior cruciate ligament) N2 - 61 a93591 27-SY-1 Regenerative silk ligament: scale up and regulatory strategy of a textile engineered silk implant for tissue regeneration of injured human ACL (anterior cruciate ligament) Bernhard Küenburg，Andreas Teuschl MorphoMed, Austria In the USA around 370.000 annual ACL ruptures in the predominately young population (age 18-30) following sport injuries cause a lot of pain and long term troubles for the affected patients. The well established standard procedure of autologous tissue transplantation stabilizes the knee and allows sport activities after 9-12 months. However, harvest of autologous tissue such as patellar tendon or semitendinosus (the most frequently used autograft) weakens other body areas and long term data show an increased rate of arthroses (up to 50% after 10 years) associated with ACL reconstructions. Based on numerous preclinical data and data from a 12-month sheep study the scale-up as well as regulatory approval process of a novel textile engineered silk implant as ACL graft have been initiated. It is planned to enter a clinical trial and strive for regulatory approval as a medical class 3 implant. The sheep data (1) have revealed an approximately 50% degradation of the purified medical silk, which acts as scaffold for the regrowth of a new endogenous ligament. The formation of oriented collagenous tissue fibers including vascularization proves a ligament tissue regeneration for the first time. Scale-up and implementation of a commercial process require a defined set of specifications of commercial silkworm (Bombyx mori) silk, a biological raw material sourced from the textile industry as well as adequate analytical methods to characterize the depletion of sericin in the course of the production process. Based on first full scale samples, the defined biocompatibility program has to be executed, in the EU following the ISO requirements of the notified bodies, in the USA determined by the FDA. Upon submission of the full technical documentation as well as the biocompati-bility data, approval of a clinical trial can be achieved in order to demonstrate the clinical efficacy of the silk based ACL graft compared to the gold standard method in two different randomized groups. As primary endpoint the knee stability will be tested by an apparatus supported Lachmann test. In this study, besides the clinical benefit the patient safety is an important goal. The results of this study will be used for achievement of regulatory approval. References: 1) Teuschl A, Heimel P, Nürnberger S, van Griensven M, Redl H, Nau T. Am. J. Sports Med. 2016;44:1547–57. 2) Teuschl AH, van Griensven M, Redl H. Tissue Eng. Part C Methods. 2014;20:431–9. KW - Biomaterial KW - Ligament Y1 - ER - TY - JOUR A1 - Tallian, Claudia A1 - Herrero-Rollett, Alexandra A1 - Stadler, Karina A1 - Vielnascher, Robert A1 - Wieland, Karin A1 - Weihs, Anna A1 - Pellis, Alessandro A1 - Teuschl, Andreas A1 - Lendl, Bernhard A1 - Amenitsch, Heinz A1 - Guebitz, Georg M. T1 - Structural insights into pH-responsive drug release of self-assembling human serum albumin-silk fibroin nanocapsules. JF - European Journal of Pharmaceutics and Biopharmaceutics N2 - Inflammation processes are associated with significant decreases in tissue or lysosomal pH from 7.4 to 4, a fact that argues for the application of pH-responsive drug delivery systems. However, for their design and optimization a full understanding of the release mechanism is crucial. In this study we investigated the pH-depending drug release mechanism and the influence of silk fibroin (SF) concentration and SF degradation degree of human serum albumin (HSA)-SF nanocapsules. Sonochemically produced nanocapsules were investigated regarding particle size, colloidal stability, protein encapsulation, thermal stability and drug loading properties. Particles of the monodisperse phase showed average hydrodynamic radii between 438 and 888 nm as measured by DLS and AFM and a zeta potential of -11.12 ± 3.27 mV. Together with DSC results this indicated the successful production of stable nanocapsules. ATR-FTIR analysis demonstrated that SF had a positive effect on particle formation and stability due to induced beta-sheet formation and enhanced crosslinking. The pH-responsive release was found to depend on the SF concentration. In in-vitro release studies, HSA-SF nanocapsules composed of 50% SF showed an increased pH-responsive release for all tested model substances (Rhodamine B, Crystal Violet and Evans Blue) and methotrexate at the lowered pH of 4.5 to pH 5.4, while HSA capsules without SF did not show any pH-responsive drug release. Mechanistic studies using confocal laser scanning microscopy (CLSM) and small angle X-ray scattering (SAXS) analyses showed that increases in particle porosity and decreases in particle densities are directly linked to pH-responsive release properties. Therefore, the pH-responsive release mechanism was identified as diffusion controlled in a novel and unique approach by linking scattering results with in vitro studies. Finally, cytotoxicity studies using the human monocytic THP-1 cell line indicated non-toxic behavior of the drug loaded nanocapsules when applied in a concentration of 62.5 µg mL-1. KW - Biomaterial KW - Tissue Engineering Y1 - ER - TY - GEN A1 - Teuschl, Andreas A1 - Schuh, Christina A1 - Weihs, Anna A1 - Guillaume, Olivier A1 - Monforte Vila, Xavier A1 - Redl, Heinz A1 - Kaplan, David A1 - Rünzler, Dominik T1 - Tailoring bioactivity of silk-based biomaterials via delivering and functionalization strategies with fibrinogen/thrombin, plant lectins or laminin KW - Biomaterials KW - Tissue Engineering KW - Silk Y1 - ER - TY - JOUR A1 - Slezak, Paul A1 - Slezak, Cyrill A1 - Hartinger, Joachim A1 - Teuschl, Andreas A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Mittermayr, Rainer T1 - A Low Cost Implantation Model in the Rat That Allows a Spatial Assessment of Angiogenesis. JF - Frontiers in Bioengineering and Biotechnology N2 - There is continual demand for animal models that allow a quantitative assessment of angiogenic properties of biomaterials, therapies, and pharmaceuticals. In its simplest form, this is done by subcutaneous material implantation and subsequent vessel counting which usually omits spatial data. We have refined an implantation model and paired it with a computational analytic routine which outputs not only vessel count but also vessel density, distribution, and vessel penetration depth, that relies on a centric vessel as a reference point. We have successfully validated our model by characterizing the angiogenic potential of a fibrin matrix in conjunction with recombinant human vascular endothelial growth factor (rhVEGF165). The inferior epigastric vascular pedicles of rats were sheathed with silicone tubes, which were subsequently filled with 0.2 ml of fibrin and different doses of rhVEGF165, centrically embedding the vessels. Over 4 weeks, tissue samples were harvested and subsequently immunohistologically stained and computationally analyzed. The model was able to detect variations over the angiogenic potentials of growth factor spiked fibrin matrices. Adding 20 ng of rhVEGF165 resulted in a significant increase in vasculature while 200 ng of rhVEGF165 did not improve vascular growth. Vascularized tissue volume increased during the first week and vascular density increased during the second week. Total vessel count increased significantly and exhibited a peak after 2 weeks which was followed by a resorption of vasculature by week 4. In summary, a simple implantation model to study in vivo vascularization with only a minimal workload attached was enhanced to include morphologic data of the emerging vascular tree. KW - Tissue Engineering KW - Bioreactor KW - Biomaterial Y1 - ER - TY - JOUR A1 - Berkovitch, Yulia A1 - Cohen, Talia A1 - Peled, Eli A1 - Schmidhammer, Robert A1 - Hildner, Florian A1 - Teuschl, Andreas A1 - Wolbank, Susanne A1 - Yelin, Dvir A1 - Redl, Heinz A1 - Seliktar, Dror T1 - Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration. JF - Journal of Tissue Engineering and Regenerative Medicine N2 - Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi-synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo-patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser-ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo-patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process. KW - Tissue Engineering KW - Biomaterials KW - Nerve Regeneration Y1 - SP - 1049 EP - 1061 ER - TY - JOUR A1 - Nau, Thomas A1 - Teuschl, Andreas A1 - Ebner, Anna A1 - Jung, Ilse A1 - Schenk, Christian T1 - Low revision rate and excellent outcome of primary ACL repair with a minimum follow-up of 5 years. JF - Muscle, ligaments and tendons Journal N2 - Introduction: Due to limitations of ACL reconstruction, primary ACL repair has recently regained research interest. Although abandoned in the past, primary repair with conservation of the original ligament demonstrates considerable advantages compared to reconstruction. We hypothesized that early repair, strictly limited to patients with a proximal ACL rupture and excellent tissue quality of the remaining ACL stump, would lead to equal revision rates and subjective outcomes as reported for ACL reconstruction after a minimum of 5 years. Methods: In this questionnaire study, patients who had a primary ACL repair between 2002 and 2009 were invited to participate. Besides any potential revision surgery, the Tegner activity scale and the Knee Injury and Osteoarthritis Outcome Score were included in the evaluation. Results: Out of 1912 patients who had ACL related surgery during the observation period, 221 (11.4%) had a primary ACL repair. 60 patients (61 knees) were available for follow-up. In 2/61 (3.3%) cases ACL revision surgery was performed and one patient had meniscus surgery of the affected side. The median Tegner activity scale was 6 (range, 3 to 10). The mean KOOS subscores were 88.8% (Function/Sports), 86.6% (Quality of life), 94.6 (Symptoms), 94.0 (Pain) and 97.0 (Activities of Daily Living). Conclusion: Primary ACL repair, strictly limited to proximal ruptures with good tissue quality leads to revision rates and subjective outcome comparable to ACL reconstruction. Level of evidence: IV. KW - Regeneration Y1 - SP - 185 EP - 190 ER - TY - GEN A1 - Teuschl, Andreas A1 - Heimel, Patrick A1 - Monforte Vila, Xavier A1 - Nürnberger, Sylvia A1 - Tangl, Stefan A1 - van Griensven, Martijn A1 - Redl, Heinz A1 - Nau, Thomas T1 - Anterior cruciate ligament regeneration using the silk-based RegACL scaffold KW - Tissue Engineering KW - Silk KW - Biomaterial KW - Anterior Cruciate Ligament Y1 - ER - TY - CHAP A1 - Hackethal, Johannes A1 - Schuh, Christina A1 - Hofer, Alexandra A1 - Meixner, Barbara A1 - Hennerbichler, Simone A1 - Redl, Heinz A1 - Teuschl, Andreas T1 - Human Placenta Laminin-111 as a Multifunctional Protein for Tissue Engineering and Regenerative Medicine T2 - Advances in Experimental Medicine and Biology KW - Biomaterial KW - Tissue Engineering KW - Regenerative medicine Y1 - PB - Springer ER - TY - GEN A1 - Salzer, Elias A1 - Rieder, Bernhard A1 - Monforte Vila, Xavier A1 - Weihs, Anna A1 - Rünzler, Dominik A1 - Teuschl, Andreas T1 - Evaluation of a novel hydrostatic pressure bioreactor on bovine cartilage chips KW - Bioreactor KW - Tissue Engineering KW - Cartilage Y1 - ER - TY - GEN A1 - Slezak, Paul A1 - Rose, Roland A1 - Hercher, David A1 - Weihs, Anna A1 - Fuchs, Christiane A1 - Redl, Heinz A1 - Mittermayr, Rainer A1 - Slezak, Cyrill T1 - Tracking therapeutic shockwaves and their impact on regeneration KW - Shockwave Therapy KW - Tissue Regeneration Y1 - ER - TY - GEN A1 - Eisner, Katharina A1 - Gepp, Barbara A1 - Schnegg, Raimund A1 - Dallinger, Reinhard A1 - Rünzler, Dominik T1 - Investigation of endocrine effects of sublethal cadmium doses on the reproduction system of the freshwater snail B. glabrata KW - Ecotoxicology KW - Endocrine disruptors Y1 - ER - TY - GEN A1 - Salzer, Elias A1 - Liousia, Varvara A1 - Monforte Vila, Xavier A1 - Rünzler, Dominik T1 - Tracking of small aquatic organisms with custom-made tracking plates KW - Ecotoxicology KW - Behavior Analysis KW - Aquatic Ecotoxicology Y1 - ER - TY - JOUR A1 - Hackethal, Johannes A1 - Mühleder, Severin A1 - Hofer, Alexandra A1 - Schneider, Karl Heinrich A1 - Prüller, Johanna A1 - Hennerbichler, Simone A1 - Redl, Heinz A1 - Teuschl, Andreas T1 - An Effective Method of Atelocollagen Type 1/3 Isolation from Human Placenta and Its In Vitro Characterization in Two-Dimensional and Three-Dimensional Cell Culture Applications JF - Tissue Eng Part C Methods KW - Placenta KW - In Vitro KW - Cell Culture Y1 - 2018 VL - 23 IS - 5 SP - 274 EP - 285 ER - TY - CHAP A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Szwarc, Dorota A1 - Mittermayr, Rainer A1 - Rünzler, Dominik A1 - Teuschl, Andreas T1 - Shock wave treatment of muscle (stem) cells - a new implementation for regeneration T2 - Proceedings of the 20th International Congress of the ISMST KW - Shockwave treatment KW - Muscle Cells KW - Regeneration Y1 - 2018 ER - TY - RPRT A1 - Freistetter, Florian T1 - The Power of Lauf KW - Bioreactor KW - Muscle KW - Tissue Engineering Y1 - ER - TY - JOUR A1 - Berkovitch, Yulia A1 - Cohen, Talia A1 - Peled, Eli A1 - Schmidhammer, Robert A1 - Hildner, Florian A1 - Teuschl, Andreas A1 - Wolbank, Susanne A1 - Yelin, Dvir A1 - Redl, Heinz A1 - Seliktar, Dror T1 - Hydrogel Composition and Laser Micro-Patterning to Regulate Sciatic Nerve Regeneration JF - Journal of Tissue Engineering and Regenerative Medicine KW - Micro-Patterning KW - Laser KW - Nerve Regeneration Y1 - 2018 VL - 12 IS - 4 ER - TY - GEN A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Szwarc, Dorota A1 - Mittermayr, Rainer A1 - Rünzler, Dominik A1 - Teuschl, Andreas T1 - Shock wave treatment of muscle (stem) cells - a new implementation for regeneration KW - Shockwave treatment KW - Muscle Cells KW - Regeneration Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Weihs, Anna A1 - Fuchs, Christiane A1 - Monforte Vila, Xavier T1 - Silk as a versatile biomaterial for musculoskeletal tissue engineering KW - Silk KW - Biomaterials Y1 - 2018 ER - TY - GEN A1 - Szwarc, Dorota A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Rünzler, Dominik T1 - Molecular mechanisms underlying the potential of shock wave treatment for cardiac therapy KW - Shockwave treatment KW - Cardiac Y1 - 2018 ER - TY - GEN A1 - Szwarc, Dorota A1 - Fuchs, Christiane A1 - Purtscher, Michaela A1 - Rünzler, Dominik T1 - Elucidating the molecular mechanisms underlying cardiac shock wave therapy KW - Shockwave treatment KW - Cardiac Y1 - 2018 ER - TY - JOUR A1 - Bernhard, Jonathan A1 - Ferguson, James A1 - Rieder, Bernhard A1 - Heimel, Patrick A1 - Nau, Thomas A1 - Tangl, Stefan A1 - Redl, Heinz A1 - Vunjak-Novakovic, Gordana T1 - Tissue-engineered hypertrophic chondrocyte grafts enhanced long bone repair biomaterials JF - Biomaterials KW - Grafting KW - Biomaterials Y1 - 2018 IS - 139 SP - 202 EP - 212 ER - TY - GEN A1 - Rünzler, Dominik T1 - Alternatives to Animal Experiment Models: Tracking Zebrafish Larvae and Daphnia KW - Animal Experiments KW - Zebrafish Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane T1 - The importance of mechanotransduction in myogenesis KW - Mechanotransduction KW - Myogenesis Y1 - 2018 ER - TY - JOUR A1 - Schneider, Cornelia A1 - Lehmann, Johannes A1 - van Osch, Gerjo A1 - Hildner, Florian A1 - Teuschl, Andreas A1 - Monforte Vila, Xavier A1 - Miosga, David A1 - Heimel, Patrick A1 - Priglinger, Eleni A1 - Redl, Heinz A1 - Wolbank, Susanne A1 - Nürnberger, Sylvia T1 - Systematic Comparison of Protocols for the Preparation of Human Articular Cartilage for Use as Scaffold Material in Cartilage Tissue Engineering JF - Tissue Eng Part C Methods KW - Cartilage KW - Scaffold Material Y1 - 2018 VL - 22 IS - 12 ER - TY - CHAP A1 - Maleiner, Babette A1 - Heher, Philipp A1 - Teuschl, Andreas A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Fuchs, Christiane T1 - Generation of aligned skeletal muscle-like tissue based on the application of strain to a 3D fibrin scaffold T2 - Proceedings of PACT "Designer Cells go Clinical" Symposium KW - Tissue Generation KW - Fibrin KW - Scaffold Y1 - 2018 ER - TY - GEN A1 - Szwarc, Dorota A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Monforte Vila, Xavier A1 - Hanetseder, Dominik A1 - Teuschl, Andreas A1 - Rünzler, Dominik T1 - The effect of shock waves on in vitro cartilage development in silk scaffolds KW - Shockwave treatment KW - In Vitro KW - Cartilage KW - Silk Y1 - 2018 ER - TY - GEN A1 - Maleiner, Babette A1 - Heher, Philipp A1 - Teuschl, Andreas A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Fuchs, Christiane T1 - Generation of aligned skeletal muscle-like tissue based on the application of strain to a 3D fibrin scaffold KW - Tissue Generation KW - Fibrin KW - Scaffold Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Heimel, Patrick A1 - Rünzler, Dominik A1 - Redl, Heinz A1 - Nau, Thomas T1 - The Silk Road from Textiles to Novel Medical Implants KW - Silk Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Heimel, Patrick A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Nau, Thomas T1 - ACL Regeneration using a novel silk fiber based scaffold - Histological Results of a Large Animal Study KW - Tissue Regeneration KW - Silk KW - Scaffold Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas T1 - Silk Processing - from Gels to ACL Replacement KW - Silk Y1 - 2018 ER - TY - CHAP A1 - Fuchs, Christiane A1 - Szwarc, Dorota A1 - Weihs, Anna A1 - Rünzler, Dominik T1 - Shock wave treatment of 3D cardiac model systems activates ERK 1/2 signaling pathway and influences cardiomyogenesis T2 - Proceedings of PACT "Designer Cells go Clinical" Symposium KW - Shockwave treatment KW - Cardiac Y1 - 2018 ER - TY - CHAP A1 - Fuchs, Christiane A1 - Szwarc, Dorota A1 - Weihs, Anna A1 - Rünzler, Dominik T1 - Shock wave treatment of 3D cardiac model systems activates ERK 1/2 signaling pathway and influences cardiomyogenesis T2 - Proceedings of LBG Meeting for Health Sciences 2016 KW - Shockwave treatment KW - Cardiac Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane A1 - Szwarc, Dorota A1 - Weihs, Anna A1 - Rünzler, Dominik T1 - Shock wave treatment of 3D cardiac model systems activates ERK 1/2 signaling pathway and influences cardiomyogenesis KW - Shockwave treatment KW - Cardiac Y1 - 2018 ER - TY - CHAP A1 - Fuchs, Christiane A1 - Szwarc, Dorota A1 - Weihs, Anna A1 - Rünzler, Dominik T1 - Shock wave treatment positively influences cardiomyogenesis in an energy-dependent manner T2 - Proceedings of PACT "Designer Cells go Clinical" Symposium KW - Shockwave treatment KW - Cardiac Y1 - 2018 ER - TY - GEN A1 - Weihs, Anna T1 - Shock wave treatment for in vitro tissue engineering applications KW - Shockwave treatment KW - In Vitro KW - Tissue Engineering Y1 - 2018 ER - TY - CHAP A1 - Basoli, Valentina A1 - Chaudry, Sidrah A1 - Cruciani, Sara A1 - Fuchs, Christiane A1 - Rieger, Sabine A1 - Dungel, Peter A1 - Wolbank, Susanne A1 - Ventura, Carlo A1 - Grillari-Voglauer, Regina A1 - Redl, Heinz A1 - Maioli, Margherita T1 - Epigenetic and molecular behavious of stem cells exposed to biophysical stimuli: new insights in regenerative medicine T2 - Proceedings des Seminars zum 40. Jahresjubiläum der Österreichischen Gesellschaft für Chirurgische Forschung KW - Stem Cells KW - Regeneration KW - Biophysical Stimuli Y1 - 2018 ER - TY - GEN A1 - Basoli, Valentina A1 - Chaudry, Sidrah A1 - Cruciani, Gabriele A1 - Fuchs, Christiane A1 - Rieger, Sabine A1 - Dungel, Peter A1 - Wolbank, Susanne A1 - Ventura, Carlo A1 - Grillari-Voglauer, Regina A1 - Redl, Heinz A1 - Maioli, Margherita T1 - Epigenetic and molecular behavious of stem cells exposed to biophysical stimuli: new insights in regenerative medicine KW - Stem Cells KW - Regeneration KW - Biophysical Stimuli Y1 - 2018 ER - TY - GEN A1 - Hofstätter, Otto A1 - Breyer, Peter A1 - Kafka, Patricia A1 - Sabo, Anton T1 - Development of a prototype for the simulation of human sway to make standardized and reproducible measurements of force and pressure sensors KW - Simulation KW - Human Sway Y1 - 2018 ER - TY - GEN A1 - Höttinger, Hannes A1 - Mally, Franziska A1 - Sabo, Anton T1 - Activity recognition in surfing - a comparative study between hidden markov model and support vector machine KW - Activity KW - Surfing Y1 - 2018 ER - TY - GEN A1 - Weihs, Anna T1 - Shock wave treatment for in vitro tissue engineering applications KW - Shockwave treatment KW - In Vitro KW - Tissue Engineering Y1 - 2018 ER - TY - GEN A1 - Weihs, Anna T1 - Mechanotransduction in shock wave treatment KW - Shockwave treatment KW - Mechanotransduction Y1 - 2018 ER - TY - GEN A1 - Mandt, Denise A1 - Pichler, Verena A1 - Melchior, Sophie A1 - Rünzler, Dominik T1 - Establishment of 2D and 3D cell culture assays using RT-gillW1 cells KW - Cell Culture KW - Assay Y1 - 2018 ER - TY - GEN A1 - Öttl, Georg A1 - Mally, Franziska A1 - Sabo, Anton T1 - The influence of low-friction quickdraws on impact forces in climbing falls KW - Climbing KW - Falling Y1 - 2018 ER - TY - GEN A1 - Salzer, Elias A1 - Rünzler, Dominik T1 - Acute Immobilization Test with Daphnia magna - A Refined Methodology for the Detection of Immobilization KW - Immobilization Y1 - 2018 ER - TY - GEN A1 - Salzer, Elias A1 - Rünzler, Dominik T1 - Live or dead is not enough: a large-scale mobility assay with Daphnia magna KW - Mobility Assay Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane T1 - A mechanical stimulation strategy for engineering skeletal muscle-like tissue on a strained fibrin scaffold KW - Muscle Tissue KW - Fibrin KW - Scaffold Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane T1 - The beneficial effects of in vitro shock wave treatment on cardiomyogenesis are energy dependent KW - In Vitro KW - Shockwave treatment KW - Myogenesis Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane T1 - Mechanotransduction - bioreactors KW - Bioreactors Y1 - 2018 ER - TY - JOUR A1 - Heher, Philipp A1 - Maleiner, Babette A1 - Prüller, Johanna A1 - Teuschl, Andreas A1 - Kollmitzer, Josef A1 - Monforte Vila, Xavier A1 - Wolbank, Susanne A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Fuchs, Christiane T1 - A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain JF - Acta Biomaterialia KW - Bioreactor Y1 - ER - TY - JOUR A1 - Teuschl, Andreas A1 - Schuh, Christina A1 - Halbweis, Robert A1 - Pajer, Krisztian A1 - Marton, Gabor A1 - Hopf, Rudolf A1 - Mosia, Shorena A1 - Rünzler, Dominik A1 - Redl, Heinz A1 - Nogradi, Antal A1 - Hausner, Thomas T1 - A new preparation method for anisotropic silk fibroin nerve guidance conduits and its evaluation in vitro and in a rat sciatic nerve defect model JF - Tissue Engineering Part C: Methods KW - Fibrin KW - Nerve Defect Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Schuh, Christina A1 - Halbweis, Robert A1 - Marton, Gábor A1 - Pajer, Krisztián A1 - Hopf, Rudolf A1 - Mosia, Shorena A1 - Rünzler, Dominik A1 - Nógrádi, Antal A1 - Hausner, Thomas A1 - Redl, Heinz T1 - Silk fibroin for peripheral nerve regeneration: a novel preparation method improved mechanical characteristics and supports regeneration in rat sciatic nerves KW - Fibroin KW - Regeneration Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Teuschl, Andreas A1 - Hartinger, Joachim A1 - Slezak, Paul A1 - Mittermayr, Rainer A1 - Redl, Heinz A1 - Junger, Wolfgang A1 - Sitte, Harald A1 - Rünzler, Dominik T1 - Shockwave Treatment Enhances Proliferation and Improves Wound Healing via Purinergic Signaling Linked ERK 1/2 Pathways KW - Shockwave treatment KW - Healing Processes KW - Signaling Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Teuschl, Andreas A1 - Hartinger, Joachim A1 - Slezak, Paul A1 - Mittermayr, Rainer A1 - Redl, Heinz A1 - Junger, Wolfgang A1 - Sitte, Harald A1 - Rünzler, Dominik T1 - Shockwave Treatment Augments Proliferation and Improves Wound Healing via Purinergic Signaling Linked ERK 1/2 Pathways KW - Shockwave treatment KW - Healing Processes KW - Signaling Y1 - 2018 ER - TY - GEN A1 - Heher, Philipp A1 - Fuchs, Christiane A1 - Prüller, Johanna A1 - Babette, Maleiner A1 - Rünzler, Dominik A1 - Redl, Heinz T1 - A novel bioreactor for engineering skeletal muscle-like tissue in a strained fibrin scaffold KW - Bioreactor KW - Scaffold KW - Muscle Tissue Y1 - ER - TY - JOUR A1 - Guillaume, Olivier A1 - Park, Jaesung A1 - Monforte Vila, Xavier A1 - Gruber-Blum, Simone A1 - Redl, Heinz A1 - Petter-Puchner, Akexander A1 - Teuschl, Andreas T1 - Fabrication of silk mesh with enhanced cytocompatibility: preliminary in vitro investigation toward cell-based therapy for hernia repair JF - Journal of Materials Science: Materials in Medicine KW - Cytocompatibility KW - Hernia Repair Y1 - 2018 ER - TY - GEN A1 - Weihs, Anna A1 - Fuchs, Christiane A1 - Teuschl, Andreas A1 - Hartinger, Joachim A1 - Slezak, Paul A1 - Mittermayr, Rainer A1 - Redl, Heinz A1 - Junger, Wolfgang A1 - Sitte, Harald A1 - Rünzler, Dominik T1 - Shockwave treatment activates Erk1/2 pathways predominantly via P2Y receptor involvement KW - Shockwave Y1 - ER - TY - JOUR A1 - Teuschl, Andreas A1 - Heimel, Patrick A1 - Nürnberger, Sylvia A1 - van Griensven, Martijn A1 - Redl, Heinz A1 - Nau, Thomas T1 - A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep. JF - The American Journal of Sports Medicine KW - Ligament KW - Regeneration Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Fuchs, Christiane A1 - Feichtinger, Georg A1 - Heher, Philipp A1 - Heimel, Patrick A1 - Schuh, Christina A1 - Nürnberger, Sylvia A1 - Nau, Thomas A1 - Rünzler, Dominik A1 - Redl, Heinz T1 - Fibrin or Fibroin - Not only the "o" Makes the Difference KW - Fibrin KW - Fibroin Y1 - 2018 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Balmayor, Elizabeth A1 - Redl, Heinz A1 - van Griensven, Martijn A1 - Dungel, Peter T1 - Phototherapy With LED Light Modulates Healing Processes in an In Vitro Scratch Wound-Model Using 3 Different Cell Types JF - Dermatologic Surgery KW - Phototherapy KW - Healing Processes Y1 - VL - 41 IS - 2 SP - 261 EP - 268 ER - TY - JOUR A1 - Schuh, Christina A1 - Hercher, David A1 - Stainer, Michaela A1 - Hopf, Rudolf A1 - Teuschl, Andreas A1 - Schmidhammer, Robert A1 - Redl, Heinz T1 - Extracorporeal shockwave treatment: A novel tool to improve Schwann cell isolation and culture JF - Cytotherapy KW - Extracorporeal shockwave Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Nürnberger, Sylvia A1 - Heimel, Patrick A1 - Redl, Heinz A1 - Nau, Thomas T1 - Regeneration of the Anterior Cruciate Ligament Using a Silk-Fiber Based Scaffold - Histological Results KW - Tissue Regeneration KW - Ligaments KW - Scaffold Y1 - 2018 ER - TY - JOUR A1 - Nau, Thomas A1 - Redl, Heinz A1 - Teuschl, Andreas T1 - Comment on: In Vivo Evaluation of Electrospun Polycaprolactone Graft for Anterior Cruciate Ligament Engineering JF - Tissue Engineering Part A KW - Grafting KW - Ligament Y1 - 2018 ER - TY - JOUR A1 - Gauillaume, Oliver A1 - Teuschl, Andreas A1 - Gruber-Blum, Simone T1 - Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio-Functionality to Meshes JF - Advanced Healthcare Materials KW - Abdominal Wall Reinforcement Y1 - ER - TY - JOUR A1 - Nau, Thomas A1 - Teuschl, Andreas T1 - Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering JF - World Journal of Orthopedics KW - Ligament KW - Regeneration KW - Tissue Engineering Y1 - VL - 6 IS - 1 ER - TY - THES A1 - Weihs, Anna T1 - Elucidation of extracorporeal shock wave treatment triggered intracellular processes N2 - Die Wirkung von Stoßwellen auf den menschlichen Körper ist bereits seit Jahrzehnten bekannt. Ihr zerstörerisches Potential wird seit den 1980-ern zur Behandlung und Desintegration von Nierensteinen angewendet, wo die Stoßwellentherapie heutzutage die Standardbehandlung darstellt. Der erste unerwartete Effekt der Therapie - die Verdichtung des Beckenkammes - wurde schon damals bei Folgeuntersuchungen von Patienten mit Nierensteinen festgestellt. Die Beobachtung, dass Stoßwellen Effekte auf Knochen hervorrufen, ebnete den Weg für die Anwendung der Stoßwellentherapie in Bereichen abseits der Urologie. Mittlerweile wird die Stoßwellentherapie nicht nur zur Behandlung von Knochenbruchheilungsstörungen und Tendinopathien, sondern auch bei Weichteilwundheilungsstörungen eingesetzt. Trotz der vielfältigen Anwendungsgebiete ist der zugrunde liegende Wirkungsmechanismus des positiven Effekts der Stoßwellentherapie bis heute noch nicht vollständig aufgeklärt. Die Aktivierung von mechanotransduktiven Signalwegen wurde bereits teilweise in vitro und in vivo gezeigt, jedoch meist bei knöchernen Indikationen. Doch auch für die Anwendung der Stoßwellentherapie in der (verzögerten) Wundheilung ist die Aufklärung des Wirkungsmechanismus essentiell. Erst dadurch könnte diese nicht- invasive, effiziente und großteils Nebenwirkungs-freie Therapieform auch in diesem Bereich als mögliche Standardtherapieform genutzt werden. In dieser Dissertation wurde zuerst ein Set-up zur in vitro Stoßwellenanwendung optimiert. Mithilfe eines Molekül-Aufnahme Assays wurden die technischen Parameter für die in vitro Stoßwellenbehandlung festgelegt. Mit diesem in vitro Aufbau sollten daraufhin jene intrazellulären Mechanismen identifiziert werden, die von der Stoßwelle beeinflusst werden. In einem in vivo Modell sollte schlussendlich die Rolle dieser Mechanismen am wundheilungsfördernden Effekt der Stoßwelle geklärt werden. Um möglichst universelle Effekte der Stoßwelle auf intrazelluläre Signalwege zu untersuchen, wurden verschiedenste Zelllinien verwendet. Diese beinhalteten die humane U937 Monozyten Zelllinie, humane Jurkat T-Zellen, die humane MG63 Osteosarcoma Zelllinie, die murine C3H10T1/2 mesenchymale Progenitor Zelllinie sowie primäre humane mononukleäre Zellen des peripheren Blutes. Die in den proliferativen Effekt der Stowellentherapie involvierte Signalkaskade konnte darauffolgend erstmals sowohl in murinen C3H10T1/2 Zellen als auch in humanen Fettstammzellen (adipose tissue-derived stem cells) und in humanen Jurkat T-Zellen detailliert beschrieben werden. Außerdem wurde ATP als entscheidendes Signalmolekül identifiziert, welches nach Freisetzung durch Stoßwellenbehandlung mittels purinergem Signaling die Erk1/2 Signalkaskade aktiviert. Für die dadurch gesteigerte Proliferation in stoßwellenbehandelten Zellen ist die Erk1/2 Aktivierung essentiell. In einem in vivo Model für gestörte Wundheilung in der Ratte wurde die Hypothese zur entscheidenden Rolle des Erk1/2 Signalweges im wundheilungsfördernden Effekt der Stoßwelle bestätigt. In dieser Dissertation wurde gezeigt, dass die durch purinerges Signaling aktivierte Erk1/2 Signalkaskade eine entscheidende Rolle in der durch Stoßwellentherapie beschleunigten Zellproliferation in vitro und Wundheilung in vivo übernimmt. Das damit erweiterte Verständnis der Wirkungsmechanismen der Stoßwellentherapie kann zur Weiterentwicklung dieser Behandlungsform als zukünftige Standardtherapie bei Wundheilungsstörungen, wie z.B. für diabetische oder chronische Wunden, beitragen. N2 - Since the early 1980s, shock wave treatment has been the golden standard treatment option for the disintegration of kidney stones in urology. A wide range of beneficial effects of shock waves on the human body was soon identified, starting with first observations of bone densification at the iliac crest after treatment of kidney stones. Since then, the indications for shock wave therapy have conquered areas apart from the field of urology. Nowadays, shock wave therapy is used for a variety of indications such as tendinopathies or impaired bone healing. Furthermore, patients suffering from poor wound healing such as diabetic foot ulcers and also chronic, non-healing wounds are treated successfully with shock waves. Despite the versatile application fields of shock wave therapy, the general principles underlying the beneficial effect of this treatment still remain to be fully elucidated. Several in vitro and in vivo studies, mostly involving osteoblast like cells and the osteo-inductive potential of shock wave treatment, already highlighted the role of the activation of mechanotransductory signaling pathways. For the clinical application of shock wave therapy as an accepted treatment for critically healing wounds (e.g. chronic or diabetic wounds, burns), general mechanistic evidence to explain the underlying mechanisms is essential. These data would facilitate the standardized application of this non-invasive, cost efficient and low- risk bearing therapy, which can be performed in an outpatient setting. First of all, an in vitro set-up was established and the necessary technical parameters for the optimal application of shock wave treatment on cell cultures were defined in this thesis. For this purpose, a molecule uptake assay was used as a functional assay. The following aims of this study were to elucidate the effect of shock wave treatment on intracellular signaling in vitro and to ultimately describe their role in the wound healing effect of shock wave treatment in vivo. To identify universal effects of shock wave treatment on intracellular signaling mechanisms, various cell lines were used, including the human U937 monocytic cell line, a human Jurkat T-cell line, the human MG63 osteosarcoma cell line, the C3H10T1/2 mouse mesenchymal progenitor cell line as well as primary human peripheral mononuclear cells. For the first time, the affected signaling cascade leading to the proliferative effect of shock wave treatment in vitro was described in detail in mouse C3H10T1/2 cells as well as in human adipose tissue-derived stem cells and human Jurkat T-cells. Further, ATP release from shock wave treated cells was shown to initiate intracellular Erk1/2 signaling activation via purinergic signaling. The thereby ultimately increased proliferation was reported to be dependent on shock wave treatment triggered Erk1/2 pathway activation. An in vivo study on impaired wound healing in rats confirmed the hypothesis on the essential role of Erk1/2 signaling in the shock wave treatment induced wound healing effect. Data clearly indicate the crucial importance of the Erk1/2 signaling cascade in the proliferative and wound healing effect of shock wave treatment. Conclusively, purinergic signaling activated Erk1/2 signaling cascades play an essential role in the shock wave treatment induced proliferative and wound healing effect. The thereby broadened knowledge on the underlying mechanistic principles of the effect of shock wave treatment contributes to the establishment of shock wave therapy as a feasible standard treatment for soft tissue wound healing disorders such as diabetic or chronic wounds. KW - Healing KW - Shockwave Y1 - 2018 ER - TY - JOUR A1 - Rosser, Julie A1 - Calvo, Isabel Olmos A1 - Schlager, Magdalena A1 - Purtscher, Michaela A1 - Jenner, Florien A1 - Ertl, Peter T1 - Recent Advances of Biologically Inspired 3D Microfluidic Hydrogel Cell Culture Systems JF - J Cell Biol Cell Metalab KW - Hydrogel KW - Cell Culture Y1 - IS - 2 ER - TY - GEN A1 - Weihs, Anna T1 - Aufklärung des Wirkungsmechanismus der Stoßwellentherapie in der Wundheilung KW - Shockwave Y1 - ER - TY - JOUR A1 - Weihs, Anna A1 - Fuchs, Christiane A1 - Teuschl, Andreas A1 - Hartinger, Joachim A1 - Slezak, Paul A1 - Mittermayr, Rainer A1 - Redl, Heinz A1 - Junger, Wolfgang A1 - Sitte, Harald A1 - Rünzler, Dominik T1 - Shock Wave Treatment Enhances Cell Proliferation and Improves Wound Healing by ATP Release-coupled Extracellular Signal-regulated Kinase (ERK) Activation JF - The Journal of biological chemistry KW - Shockwave Y1 - ER - TY - JOUR A1 - Schuh, Christina A1 - Heher, Philipp A1 - Weihs, Anna A1 - Asmita, Banerjee A1 - Wolbank, Susanne A1 - Mittermayr, Rainer A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Teuschl, Andreas T1 - Adipose derived stem cells respond to in vitro extracorporeal shockwave treatment with increased stemness and multipotency JF - New Biotechnology KW - Shockwave Y1 - ER - TY - GEN A1 - Kroller, Theophil A1 - Kreuzinger, Norbert A1 - Rünzler, Dominik T1 - Validierung und Anwendung eines zellkultur-basierten Assays für Screening von endokrin wirksamen Stoffen in Abwasser KW - Assay KW - Sewage Water Y1 - 2018 ER - TY - GEN A1 - Guillaume, Olivier A1 - Monforte Vila, Xavier T1 - Development of a Biodegradable Silk Mesh Suitable for Intra-Operative Fast Cell Seeding KW - Silk KW - Cell Seeding Y1 - 2018 ER - TY - GEN A1 - Fuchs, Christiane T1 - Shockwave treatment promotes proliferation via purinergic signaling coupled ERK1/2 pathway activation KW - Shockwave Y1 - ER - TY - GEN A1 - Heher, Philipp A1 - Fuchs, Christiane A1 - Prüller, Johanna A1 - Maleiner, Babette A1 - Kollmitzer, Josef A1 - Rünzler, Dominik A1 - Teuschl, Andreas A1 - Wolbank, Susanne A1 - Redl, Heinz T1 - A bioreactor-based 3D culture system for skeletal muscle engineering in fibrin scaffolds KW - Bioreactors KW - Cell Culture KW - Muscle KW - Scaffold Y1 - 2018 ER - TY - JOUR A1 - Banerjee, Asmita A1 - Nürnberger, Sylvia A1 - Hennerbichler, Simone A1 - Riedl, Stefan A1 - Schuh, Christina A1 - Hacobian, Ara A1 - Teuschl, Andreas A1 - Eibl, Jürgen A1 - Redl, Heinz T1 - In toto differentiation of human amniotic membrane towards the Schwann cell lineage JF - 227-239 KW - Membrane KW - In toto differentiation Y1 - 2018 VL - 15 IS - 2 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Neutsch, Lukas A1 - Monforte Vila, Xavier A1 - Rünzler, Dominik A1 - van Griensven, Martijn A1 - Gabor, Franz A1 - Redl, Heinz T1 - Enhanced cell adhesion on silk fibroin via lectin surface modification. JF - Acta Biomaterialia KW - Silk KW - Fibrin Y1 - ER - TY - GEN A1 - Weihs, Anna T1 - Revealing underlying mechanisms of shock wave treatment induced wound healing KW - Shockwave Y1 - ER - TY - JOUR A1 - Buta, Christiane A1 - David, Robert A1 - Dressel, Ralf A1 - Emgard, Mia A1 - Fuchs, Christiane A1 - Gross, Ulrike A1 - Healy, Lyn A1 - Hescheler, Jürgen A1 - Kolar, Roman A1 - Martin, Ulrich A1 - Mikkers, Harald A1 - Müller, Franz-Josef A1 - Schneider, Rebekka A1 - Seiler, Andrea A1 - Spielmann, Horst A1 - Weitzer, Georg T1 - REconsidering pluripotency tests: do we still need teratoma assays? JF - Stem Cell Research KW - Assay KW - Stem Cells Y1 - 2018 VL - 11 IS - 1 SP - 552 EP - 562 ER - TY - JOUR A1 - Hohlrieder, Manfred A1 - Teuschl, Andreas A1 - Cicha, Klaus A1 - van Griensven, Martijn A1 - Redl, Heinz A1 - Stampfl, Jürgen T1 - Bioreactor and scaffold design for the mechanical stimulation of anterior cruciate ligament grafts JF - Biomedical materials and engineering KW - Bioreactors KW - Ligaments KW - Grafting Y1 - 2018 VL - 23 IS - 3 SP - 225 EP - 237 ER - TY - JOUR A1 - Dungel, Peter A1 - Teuschl, Andreas A1 - Banerjee, Asmita A1 - Paier-Pourani, Jamile A1 - Redl, Heinz A1 - Kozlov, Andrey T1 - Impact of mitochondria on nitrite metabolism in HL-1 cardiomyocytes JF - Frontiers in Physiology KW - Nitrite KW - Metabolism Y1 - 2018 IS - 4 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Nau, Thomas T1 - Articular cartilage tissue regeneration: current research strategies and outlook for the future JF - European Surgery KW - Tissue Regeneration KW - Cartilage Tissue Y1 - 2018 VL - 45 IS - 3 SP - 142 EP - 153 ER - TY - JOUR A1 - Teuschl, Andreas A1 - van Griensven, Martijn A1 - Redl, Heinz T1 - Sericin removal from raw Bombys mori silk scaffolds of high hierarchical order JF - Tissue Eng Part C Methods KW - Scaffold KW - Sericin Y1 - 2018 ER - TY - JOUR A1 - Schuh, Christina A1 - Banerjee, Asmita A1 - Mosia, Shorena A1 - Hopf, Rudolf A1 - Grasl, Christian A1 - Schima, Heinrich A1 - Schmidhammer, Robert A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Morton, Tatjana J. T1 - Activated Schwann-like cells guided by fibrin structures enhance Axonal Regeneration JF - JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE KW - Cells KW - Fibrin Y1 - 2019 VL - 2012 IS - vol. 6/no. 1 ER - TY - JOUR A1 - Rieder, Bernhard A1 - Weihs, Anna A1 - Teuschl, Andreas A1 - Knebl, Gerald A1 - Kollmitzer, Josef A1 - Redl, Heinz A1 - Rünzler, Dominik T1 - Evaluation of cell response on permanent and pulsed atmospheric pressure stressed cells JF - Journal of Tissue Engineering and Regenerative Medicine KW - Cells KW - Atmospheric Pressure Y1 - 2018 VL - 1 IS - 6 SP - 240 EP - 240 ER - TY - JOUR A1 - Weihs, Anna A1 - Junger, Wolfgang A1 - Schaden, Wolfgang A1 - Sitte, Harald A1 - Rünzler, Dominik T1 - Extracorporeal shockwave treatment induced extracellular ATP release - a potential mechanism to activate wound healing JF - Journal of Tissue Engineering and Regenerative Medicine KW - Shockwave treatment KW - Healing Processes Y1 - 2018 VL - 1 IS - 6 SP - 381 EP - 381 ER - TY - JOUR A1 - Rünzler, Dominik A1 - Weihs, Anna A1 - Junger, Wolfgang A1 - Sitte, Harald A1 - Schaden, Wolfgang T1 - Extracorporeal shock waves - a novel method of mechanostimulation in tissue regeneration JF - Journal of Tissue Engineering and Regenerative Medicine KW - Shockwave treatment KW - Mechanostimulation Y1 - 2018 VL - 1 IS - 6 SP - 380 EP - 380 ER - TY - JOUR A1 - Martin M., Frank A1 - Kollmitzer, Josef A1 - Redl, Heinz A1 - Rünzler, Dominik T1 - Shear force stimulation of adipose-tissue derived stem cells in a novel bioreactor JF - Journal of Tissue Engineering and Regenerative Medicine KW - Stem Cells KW - Adipose Y1 - 2018 VL - 1 IS - 6 SP - 340 EP - 340 ER - TY - GEN A1 - Weihs, Anna A1 - Junger, Wolgang G. A1 - Schaden, Wolfgang A1 - Sitte, Harald H. A1 - Rünzler, Dominik T1 - Extracellular ATP release - a potential benefit in shock wave treatment KW - Shockwave Y1 - 2019 ER - TY - JOUR A1 - Milan-Lobo, Laura A1 - Gsandtner, Ingrid A1 - Gaubitzer, Erwin A1 - Rünzler, Dominik A1 - Buchmayer, Florian A1 - Köhler, Gottfried A1 - Bonci, Antonello A1 - Freissmuth, Michael A1 - Sitte, Harald H. T1 - Subtype-specific differences in corticotropin-releasing factor receptor complexes detected by fluorescence spectroscopy JF - Molecular Pharmacology (mol pharmacol) KW - Spectroscopy Y1 - 2019 IS - 76(6) SP - 1196 EP - 1210 ER - TY - CHAP A1 - Weihs, Anna A1 - Knebl, Gerald A1 - Redl, Heinz A1 - Rünzler, Dominik T1 - Evaluation of cell migration methods in 3D hydrogels for tissue engineering applications T2 - 3. Forschungsforum der österreichischen Fachhochschulen / Fachhochschule Kärnten KW - Cells Y1 - 2019 SN - 978-3-853912850 SP - 490 EP - 491 ER - TY - GEN A1 - Weihs, Anna T1 - Establishment of an in vitro experimental set-up to evaluate the biological effects of extracorporeal shock wave treatment KW - Shockwave Y1 - 2019 ER - TY - CHAP A1 - Knebl, Gerald A1 - Weihs, Anna A1 - Weingant, Michaela A1 - Steininger, Thomas A1 - Redl, Heinz A1 - Rünzler, Dominik T1 - Automatisierte Datenauswertung eines Boyden-Mikro-Chemotaxis-Kammer Zell-Migrations Assays. T2 - 2. Forschungsforum der österreichischen Fachhochschulen KW - Cells KW - Data Analysis Y1 - 2019 SN - 978-3-8322-7023-0 SP - 412 EP - 417 ER - TY - CHAP A1 - Rünzler, Dominik A1 - Knebl, Gerald A1 - Peterbauer, A. A1 - Wolbank, Susanne A1 - Morton, Tatjana J. A1 - Redl, Heinz T1 - Darstellung fluoreszenzmarkierter adulter Stammzellen in drei-dimensionaler Zellkultur mittels Konfokaler Laser Scanning Mikroskopie T2 - Erstes Forschungsforum der österreichischen Fachhochschulen KW - Cells Y1 - 2019 SP - 311 EP - 316 ER - TY - JOUR A1 - Grunt, Thomas A1 - Tomek, Katharina A1 - Wagner, Renate A1 - Puckmair, Klaudia A1 - Kainz, Birgit A1 - Rünzler, Dominik A1 - Gaiger, Alexander A1 - Köhler, Gottfried A1 - Zielinski, Christoph T1 - Upregulation of retinoic acid receptor-beta by the epidermal growth factor-receptor inhibitor PD153035 is not mediated by blockade of ErbB pathways JF - Journal of Cell Physiology KW - Cells Y1 - 2019 IS - 211(3) SP - 803 EP - 815 ER - TY - JOUR A1 - Willerroider, Marika A1 - Fuchs, Heidemarie A1 - Ballmer-Weber, Barbara A1 - Focke, Margarete A1 - Susani, M. A1 - Thalhammer, J. T1 - Cloning and molecular and immunological characterisation of two new food allergens, Cap a 2 and Lyc e 1, profilins from bell pepper (Capsicum annuum) and tomato (Lycopersicon esculentum) JF - International Archives of Allergy and Immunology KW - Cloning KW - Immunology KW - Allergen Y1 - 2019 VL - 131 IS - 4 SP - 245 EP - 255 ER - TY - JOUR A1 - Spurny, Radovan A1 - Abdoulrahman, Kamaran A1 - Janda, Lubomir A1 - Rünzler, Dominik A1 - Köhler, Gottfried A1 - Castanon, Maria J. A1 - Wiche, Gerhard T1 - Oxidation and nitrosylation of cysteines proximal to the intermediate filament (IF)-binding site of plectin: effects on structure and vimentin binding and involvement in IF collapse JF - Journal of Biological Chemistry KW - Oxidation Y1 - 2019 IS - 282(11) SP - 8175 EP - 8187 ER - TY - GEN A1 - Rünzler, Dominik T1 - Darstellung fluoreszenzmarkierter adulter Stammzellen in drei-dimensionaler Zellkultur mittels Konfokaler Laser Scanning Mikroskopie KW - Cells Y1 - 2019 ER - TY - GEN A1 - Rünzler, Dominik T1 - Automatisierte Datenauswertung eines Boyden-Mikro-Chemotaxis-Kammer Zell-Migrations Assays KW - Cells KW - Data Analysis Y1 - 2019 ER - TY - CHAP A1 - Milan-Lobo, Laura A1 - Rünzler, Dominik A1 - Gaubitzer, Erwin A1 - Köhler, Gottfried A1 - Bonci, Antonello A1 - Freissmuth, Michael A1 - Sitte, Harald H. T1 - CRF receptors form dynamic complexes at the plasma membrane but only type 2 receptor increases lateral mobility after CRF binding T2 - FEBS Journal KW - Plasma Membrane Y1 - 2019 ER - TY - CHAP A1 - Kaisler, Raphaela A1 - Pázmándi, Christian A1 - Ortner, Anna A1 - Haberl, Ines A1 - Köhler, Gottfried A1 - Rünzler, Dominik A1 - Artl, Andreas A1 - Andreae, Fritz A1 - Mosgöller, Wilhelm T1 - Vasoactive intestinal peptide conjugate internalisation as strategy for cytoplasmic drug delivery T2 - Journal of Molecular Neuroscience KW - Cytplasmic Drug Delivery Y1 - 2019 ER - TY - JOUR A1 - Wruss, Jürgen A1 - Rünzler, Dominik A1 - Steiger, Christina A1 - Chiba, Peter A1 - Köhler, Gottfried A1 - Blaas, Dieter T1 - Attachment of VLDL receptors to an icosahedral virus along the 5-fold symmetry axis: multiple binding modes evidenced by fluorescence correlation spectroscopy JF - Biochemistry KW - Cells Y1 - 2019 IS - 46(21) SP - 6331 EP - 6339 ER - TY - JOUR A1 - Maier, Christina A1 - Rünzler, Dominik A1 - Schindelar, Julia A1 - Grabner, Gottfried A1 - Waldhäusl, Werner Klaus A1 - Köhler, Gottfried A1 - Luger, Anton T1 - G-protein-coupled glucocorticoid receptors on the pituitary cell membrane JF - Journal of Cell Science KW - Cells Y1 - 2019 IS - 118(15) SP - 3353 EP - 3361 ER - TY - JOUR A1 - Maier, Christina A1 - Rünzler, Dominik A1 - Wagner, Ludwig A1 - Grabner, Günther A1 - Köhler, Gottfried A1 - Lugner, Anton T1 - Evidence for specific glucocorticoid binding sites on the cell membrane by fluorescence correlation spectroscopy JF - Single Moleculus KW - Cells Y1 - 2019 IS - 3(4) SP - 211 EP - 216 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Aigner, Elmar A1 - Hohlrieder, Martin A1 - Cicha, Klaus A1 - Stampfl, Jürgen A1 - Redl, Heinz T1 - Stimulation of ligament tissue formation on a silk scaffold with mechanical loading using a custom-made bioreactor system JF - Journal of Tissue Engineering and Regenerative Medicine KW - Ligament KW - Tissue Formation KW - Scaffold KW - Silk KW - Bioreactor Y1 - 2018 VL - 1 IS - 6 SP - 51 EP - 51 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Ferguson, James A1 - Szomolanyi, Pavol A1 - Trattnig, Siegfried A1 - Redl, Heinz A1 - Nau, Thomas T1 - Osteointegration of anterior cruciate ligament scaffolds fabricated of bombyx mori silk JF - Journal of Tissue Engineering and Regenerative Medicine KW - Osteointegration KW - Cruciate Ligament KW - Scaffold KW - Silk Y1 - 2018 VL - 1 IS - 6 SP - 181 EP - 182 ER - TY - GEN A1 - Rünzler, Dominik A1 - Bergmann, J. A1 - Sára, Margit A1 - Köhler, Gottfried T1 - Protein-Ligand Interactions: Fluorescence Binding Assays performed with FCS and Fluorescence Anisotropy Measurements KW - Protein KW - Assay Y1 - 2019 ER - TY - GEN A1 - Maier, Christina A1 - Rünzler, Dominik A1 - Schindelar, Julia A1 - Grabner, Gottfried A1 - Luger, Anton T1 - High-Affinity Membrane Glucocorticoid Binding Sites on the Living Cell KW - Cell Membrane Y1 - 2019 ER - TY - GEN A1 - Rünzler, Dominik A1 - Sára, Margit A1 - Köhler, Gottfried T1 - Biophysical Investigations on the S-layer Protein SbsB KW - Protein Y1 - 2019 ER - TY - GEN A1 - Rünzler, Dominik T1 - Detection of Ultrafine Particles in Living Cells by using Fluorescence Correlation Spectroscopy KW - Particle Detection KW - Cells KW - Spectroscopy Y1 - 2018 ER - TY - GEN A1 - Rünzler, Dominik A1 - Maier, Christina A1 - Schindelar, Julia A1 - Grabner, Gottfried A1 - Köhler, Gottfried A1 - Luger, Anton T1 - High-affinity membrane glucocorticoid binding sites on the pituitary cell line AtT-20 characterized by Fluorescence Correlation Spectroscopy KW - Cell Y1 - 2019 ER - TY - GEN A1 - Rünzler, Dominik A1 - Maier, Christina A1 - Wagner, Ludwig A1 - Grabner, Gottfried A1 - Köhler, Gottfried A1 - Luger, Anton T1 - Evidence for specific glucocorticoid binding sites on the cell membrane of a living cell by fluorescence correlation microscopy KW - Glucocorticoid KW - Cell Membrane KW - Spectroscopy Y1 - 2019 ER - TY - GEN A1 - Rünzler, Dominik A1 - Maier, Christina A1 - Schindelar, Julia A1 - Köhler, Gottfried A1 - Luger, Anton T1 - Flourescence Correlation Spectroscopy (FCS): A New Tool for Studying Membrane Steroid Receptors KW - Spectroscopy KW - Steroid Receptors KW - Membrane Y1 - 2019 ER - TY - GEN A1 - Maier, Christina A1 - Rünzler, Dominik A1 - Wagner, Ludwig A1 - Grabner, Gottfried A1 - Luger, Anton T1 - Functional Characterization of the Putative Membrane Glucocorticoid Receptor using FCS KW - Cell Membrane KW - Glucocorticoid Y1 - 2019 ER - TY - GEN A1 - Rünzler, Dominik T1 - Investigation of Putative Membrane Glucocorticoid Binding Sites on Single Living Cells by FCS KW - Cell Membrane KW - Glucocorticoid Y1 - 2019 ER - TY - GEN A1 - Edetsberger, Michael A1 - Rünzler, Dominik A1 - Schindelar, Julia A1 - Valic, Eva A1 - Köhler, Gottfried T1 - Specific glucocorticoid binding sites on the cell membrane of AtT-20 cell line T2 - 11th Meeting of the European Neuroendocrine Association (ENEA) KW - Cell Membrane Y1 - 2019 ER - TY - JOUR A1 - Rosner, Margit A1 - Schipany, Katharina A1 - Gundacker, Claudia A1 - Shanmugasundaram, Parthasaraty A1 - Li, Kongzhao A1 - Fuchs, Christiane A1 - Lubec, Gert A1 - Hengstschläger, Martin T1 - Renal differentiation of amniotic fluid stem cells: perspectives for clinical application and for studies on specific human genetic diseases JF - Eur J Clin Invest KW - Stem Cells KW - Genetic Diseases Y1 - 2018 ER - TY - JOUR A1 - Gundacker, Claudia A1 - Scheinast, Matthias A1 - Damjanovic, Lukas A1 - Fuchs, Christiane A1 - Rosner, Margit A1 - Hengstschläger, Markus T1 - Proliferation potential of human amniotic fluid stem cells differently respondes to mercury and lead exposure JF - Amino Acids KW - Stem Cells Y1 - 2018 ER - TY - JOUR A1 - Rosner, Margit A1 - Fuchs, Christiane A1 - Dolznig, Helmut A1 - Hengstschläger, Markus T1 - Different cytoplasmic/nucelar distribution of S6 protein phosphorylated at S240/244 and S235/236 JF - Amino Acids KW - Proteins Y1 - 2018 IS - 40 SP - 595 EP - 600 ER - TY - GEN A1 - Maier, Christina A1 - Altenberger, T. A1 - Rünzler, Dominik T1 - Investigation of Putative Membrane Glucocorticoid Binding Sites on Single Living Cells by FCS KW - Cell Membrane KW - Glucocorticoid Y1 - 2019 ER - TY - GEN A1 - Edetsberger, Michael A1 - Rünzler, Dominik A1 - Schindelar, Julia A1 - Valic, Eva A1 - Köhler, Gottfried T1 - Detection of Ultrafine Particles in Living Cells KW - Cell Y1 - 2019 ER - TY - JOUR A1 - Krautwald, Stefan A1 - Büscher, Dirk A1 - Jesenberger, Veronika A1 - Buder, Sylke A1 - Baccarini, Manuela T1 - Involvement of the protein tyrosine phosphatase SHP-1 in Ras-mediated activation of the mitogen-activated protein kinase pathway. JF - Mol Cell Biol. N2 - Ubiquitously expressed SH2-containing tyrosine phosphatases interact physically with tyrosine kinase receptors or their substrates and relay positive mitogenic signals via the activation of the Ras-mitogen-activated protein kinase (MAPK) pathway. Conversely, the structurally related phosphatase SHP-1 is predominantly expressed in hemopoietic cells and becomes tyrosine phosphorylated upon colony-stimulating factor 1 treatment of macrophages without associating with the colony-stimulating factor 1 receptor tyrosine kinase. Mice lacking functional SHP-1 (me/me and me(v)/me(v)) develop systemic autoimmune disease with accumulation of macrophages, suggesting that SHP-1 may be a negative regulator of hemopoietic cell growth. By using macrophages expressing dominant negative Ras and the me(v)/me(v) mouse mutant, we show that SHP-1 is activated in the course of mitogenic signal transduction in a Ras-dependent manner and that its activity is necessary for the Ras-dependent activation of the MAPK pathway but not of the Raf-1 kinase. Consistent with a role for SHP-1 as an intermediate between Ras and the MEK-MAPK pathway, Ras-independent activation of the latter kinases by bacterial lipopolysaccharide occurred normally in me(v)/me(v) cells. Our results sharply accentuate the diversity of signal transduction in mammalian cells, in which the same signaling intermediates can be rearranged to form different pathways. KW - Molecular Cell Biology KW - protein kinase pathway KW - Ras Y1 - 2020 U6 - http://dx.doi.org/doi: 10.1128/mcb.16.11.5955 VL - 1996 IS - 16(11) SP - 5955 EP - 5963 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Procyk, Katarzyna A1 - Yuan, Junying A1 - Reipert, Siegfried A1 - Baccarini, Manuela T1 - Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis JF - J Exp Med. N2 - The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and in vivo. These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host's apoptotic machinery by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. We show that caspase-1-deficient macrophages undergo apoptosis within 4-6 h of infection with invasive bacteria. This process requires SipB, implying that this protein can initiate the apoptotic machinery by regulating components distinct from caspase-1. Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. Besides caspase-2, the caspase-1-independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of which occurs during caspase-1-dependent apoptosis. By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1-dependent and -independent apoptosis. Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. The ability of Salmonella to induce caspase-1-independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis. KW - caspase-2 activation in macrophages KW - pathogen-activated apoptosis KW - Molecular Cell Biology Y1 - 2020 U6 - http://dx.doi.org/10.1084/jem.192.7.1035 VL - 2000 IS - 192(7) SP - 1035 EP - 1046 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Procyk, Katarzyna A1 - Rüth, Jochen A1 - Schreiber, Martin A1 - Theussl, Hans Christian A1 - Wagner, Erwin A1 - Baccarini, Manuela T1 - Protective Role of Raf-1 in Salmonella-Induced Macrophage Apoptosis JF - J Exp Med. N2 - Invasive Salmonella induces macrophage apoptosis via the activation of caspase-1 by the bacterial protein SipB. Here we show that infection of macrophages with Salmonella causes the activation and degradation of Raf-1, an important intermediate in macrophage proliferation and activation. Raf-1 degradation is SipB- and caspase-1–dependent, and is prevented by proteasome inhibitors. To study the functional significance of Raf-1 in this process, the c-raf-1 gene was inactivated by Cre-loxP–mediated recombination in vivo. Macrophages lacking c-raf-1 are hypersensitive towards pathogen-induced apoptosis. Surprisingly, activation of the antiapoptotic mitogen-activated protein kinase kinase (MEK)/extracellular signal–regulated kinase (ERK) and nuclear factor κB pathways is normal in Raf-1–deficient macrophages, and mitochondrial fragility is not increased. Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis. KW - Salmonella-Induced Macrophage Apoptosis KW - Raf-1 pathway KW - Molecular Cell Biology Y1 - 2020 U6 - http://dx.doi.org/10.1084/jem.193.3.353 VL - 2001 IS - 193(3) SP - 353 EP - 364 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Jentsch, Stefan T1 - Deadly encounter: ubiquitin meets apoptosis JF - Nat Rev Mol Cell Biol. N2 - The ubiquitin/proteasome pathway is the main non-lysosomal route for intracellular protein degradation in eukaryotes. It is instrumental to various cellular processes, such as cell-cycle progression, transcription and antigen processing. Recent findings also substantiate a pivotal role of the ubiquitin/proteasome pathway in the regulation of apoptosis. Regulatory molecules that are involved in programmed cell death have been identified as substrates of the proteasome. Moreover, key regulators of apoptosis themselves seem to have an active part in the proteolytic inactivation of death executors. KW - programmed cell death KW - Molecular Cell Biology Y1 - 2020 U6 - http://dx.doi.org/https://doi.org/10.1038/nrm731 VL - 2002 IS - 3(2) SP - 112 EP - 121 ER - TY - GEN A1 - Leitner, Rita A1 - Sauermann, Stefan T1 - Erreichen „harmonisierter Empfehlungen“: von Studierenden generierte Fragen als Ausgangspunkt für evidenzbasierte Argumentation von Stakeholder-Sichtweisen – ein problem-based learning Ansatz KW - Problem Based Learning KW - Didactics KW - eHealth KW - Education Y1 - ER - TY - JOUR A1 - Huber-Gries, Carina A1 - Ilk, Nicola A1 - Rünzler, Dominik A1 - Egelseer, Eva-Maria A1 - Weigert, Stefan A1 - Sleytr, Uwe T1 - The three S-layer-like homology motifs of the S-layer protein SbpA of Bacillus sphaericus CCM 2177 are not sufficient for binding to the pyruvylated secondary cell wall polymer JF - Molecular Microbiology KW - Proteins Y1 - 2018 VL - 55 IS - 1 SP - 197 EP - 205 ER - TY - GEN A1 - Thiele, Gerrit A1 - Kafka, Patricia A1 - Litzenberger, Stefan A1 - Sabo, Anton T1 - Ontrack measurements in motocross: The correlation of neck muscle activity and contact incidents of helmet and neck brace KW - Motocross KW - Neck Y1 - 2018 ER - TY - JOUR A1 - Tomasch, Janine A1 - Maleiner, Babette A1 - Hromada, Carina A1 - Szwarc-Hofbauer, Dorota A1 - Teuschl-Woller, Andreas T1 - Cyclic Tensile Stress Induces Skeletal Muscle Hypertrophy and Myonuclear Accretion in a 3D Model JF - Tissue Eng. Part A. N2 - Skeletal muscle is highly adaptive to mechanical stress due to its resident stem cells and the pronounced level of myotube plasticity. Herein, we study the adaptation to mechanical stress and its underlying molecular mechanisms in a tissue-engineered skeletal muscle model. We subjected differentiated 3D skeletal muscle-like constructs to cyclic tensile stress using a custom-made bioreactor system, which resulted in immediate activation of stress-related signal transducers (Erk1/2, p38). Cell cycle re-entry, increased proliferation, and onset of myogenesis indicated subsequent myoblast activation. Furthermore, elevated focal adhesion kinase and β-catenin activity in mechanically stressed constructs suggested increased cell adhesion and migration. After 3 days of mechanical stress, gene expression of the fusogenic markers MyoMaker and MyoMixer, myotube diameter, myonuclear accretion, as well as S6 activation, were significantly increased. Our results highlight that we established a promising tool to study sustained adaptation to mechanical stress in healthy, hypertrophic, or regenerating skeletal muscle. KW - fibrin KW - tissue engineering KW - tensile stress KW - regeneration KW - hypertrophy Y1 - VL - 2023 IS - Mar SP - 257 EP - 268 ER - TY - GEN A1 - Egelseer, Eva-Maria A1 - Völlenkle, Christine A1 - Pleschberger, Magdalena A1 - Moll, Dieter A1 - Ilk, Nicola A1 - Huber-Gries, Carina A1 - Breitwieser, A. A1 - Sleytr, Uwe A1 - Sára, Margit T1 - The relevance of S-layer fusion proteins in nanotechnology KW - Protein KW - Nanotechnology KW - Nanobiology Y1 - 2019 ER - TY - GEN A1 - Stoiber, Stefan A1 - Purtscher, Michaela A1 - Gepp, Barbara A1 - Huber-Gries, Carina T1 - Towards a platform for spatially defined cell characterization of a miniturized heart tissue model KW - Microfluidic KW - Tissue Engineering KW - Heart Y1 - ER - TY - GEN A1 - Purtscher, Michaela A1 - Ergir, Ece A1 - Szwarc, Dorota A1 - Monforte Vila, Xavier A1 - Rünzler, Dominik A1 - Huber-Gries, Carina T1 - A microfluidic-based easy-to-use cardiac tissue model for drug screening applications KW - Tissue Generation KW - Drug Screening KW - Cardiac Y1 - 2018 ER - TY - GEN A1 - Purtscher, Michaela A1 - Ergir, Ece A1 - Monforte Vila, Xavier A1 - Huber-Gries, Carina T1 - Establishment of an in vitro heart tissue model for pre-clinical screening of therapeutic agents using microfluidic technology KW - Tissue Generation KW - Heart Tissue Y1 - 2018 ER - TY - GEN A1 - Purtscher, Michaela A1 - Ergir, Ece A1 - Szwarc, Dorota A1 - Huber-Gries, Carina T1 - Microfluidic based heart-tissue model for directed development of cardiac specific cell types KW - Heart Tissue KW - Tissue Generation KW - Cardiac Y1 - 2018 ER - TY - GEN A1 - Hromada, Carina A1 - Tomasch, Janine A1 - Weihs, Anna A1 - Rünzler, Dominik A1 - Teuschl, Andreas T1 - Engineering of 3D Tissue Constructs Using our Novel MagneTissue Bioreactor as Alternatives to Animal Models KW - Bioreactor KW - Biomaterials Y1 - ER - TY - GEN A1 - Litzenberger, Stefan A1 - Mally, Franziska A1 - Braunstein, Björn A1 - Willwacher, Steffen A1 - Sabo, Anton A1 - Brüggemann, Gert-Peter T1 - Influence of weighted cuffs on ground reaction forces in running of an elite unilateral upper extremity amputee athlete. KW - Amputation KW - Running Y1 - 2018 ER - TY - GEN A1 - Litzenberger, Stefan A1 - Mally, Franziska A1 - Willwacher, Steffen A1 - Braunstein, Björn A1 - Sabo, Anton A1 - Brüggemann, Gert-Peter T1 - Einfluss einer unilateralen Dysmelie des Unterarms auf die Bodenreaktionskräfte eines 800m Läufers KW - Running Y1 - 2018 ER - TY - GEN A1 - Felsner, Eduard-Max A1 - Litzenberger, Stefan A1 - Mally, Franziska A1 - Sabo, Anton T1 - Musculoskeletal modelling of elite handcycling motion: Evaluation of muscular on- and offset KW - Handcycling Y1 - 2018 ER - TY - GEN A1 - Litzenberger, Stefan A1 - Sabo, Anton A1 - Fuss, Franz Konstantin T1 - Effect of different mounting angles of prosthetic feet dedicated to sprinting on reaction forces KW - Prothesis KW - Running Y1 - 2018 ER - TY - JOUR A1 - Leeb, Christine A1 - Leitner, Rita A1 - Pichler, Verena A1 - Huber-Gries, Carina A1 - Rünzler, Dominik A1 - Jesenberger, Veronika T1 - Einführung und Optimierung eines praxisorientierten PBL-Moduls im Life-Science-Bereich JF - Zeitschrift für Hochschulentwicklung (ZFHE) KW - Life Science KW - Problem Based Learning KW - Education Y1 - 2018 VL - 11 IS - 3 SP - 107 EP - 121 ER - TY - JOUR A1 - Rieder, Bernhard A1 - Weihs, Anna A1 - Weidinger, Adelheid A1 - Sczwarc, Dorota A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Huber-Gries, Carina A1 - Teuschl, Andreas T1 - Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures JF - Scientific Reports KW - Bioreactor KW - Osteoarthritis KW - Cartilage KW - Reactive oxygen species Y1 - ER - TY - JOUR A1 - Teuschl, Andreas A1 - Zipperle, Johannes A1 - Huber-Gries, Carina A1 - Kaplan, David T1 - Silk fibroin based carrier system for delivery of fibrinogen and thrombin as coagulant supplements JF - Journal of Biomedical Materials Research KW - Fibrin KW - Silk Y1 - 2018 VL - 105 IS - 3 ER - TY - CHAP A1 - Huber-Gries, Carina A1 - Moll, Dieter A1 - Liu, Jing A1 - Rünzler, Dominik A1 - Sára, Margit A1 - Sleytr, Uwe T1 - S-layer-streptavidin fusion proteins: Novel Tools in Nanobiotechnology T2 - 6th Annual Linz Winter Workshop - Book of Abstracts KW - Proteins KW - Nanobiology KW - Nanotechnology Y1 - 2019 SP - 11 EP - 11 ER - TY - JOUR A1 - Huber-Gries, Carina T1 - Heterotetramers Formed by an S‐Layer–Streptavidin Fusion Protein and Core‐Streptavidin as a Nanoarrayed Template for Biochip Development JF - Small KW - Biochips KW - Protein Y1 - 2018 VL - 2 IS - 1 SP - 142 EP - 150 ER - TY - JOUR A1 - Sleytr, Uwe B. A1 - Huber-Gries, Carina A1 - Nicola, Ilk A1 - Puhm, Dietmar A1 - Schuster, Bernhard A1 - Egelseer, Eva-Maria T1 - S-layers as a tool kit for nanobiotechnological applications JF - FEMS Microbiology Letters KW - Nanobiotechnology Y1 - 2019 IS - 267(2) ER - TY - GEN A1 - Kamravamanesh, Donya A1 - Pflügl, Stefan A1 - Herwig, Christoph A1 - Lackner, Maximilian T1 - Optimization of process parameters to enhance PHA accumulation in Synechosystis sp. PCC 6714 using multivariate design of experiments KW - Bacteria Y1 - 2018 ER - TY - JOUR A1 - Ebner, Andreas A1 - Kienberger, Ferry A1 - Huber-Gries, Carina A1 - Kamruzzahan, A.S.M. A1 - Pastushenko, Vassili A1 - Tang, Jilin A1 - Kada, Gerald A1 - Gruber, Hermann A1 - Sleytr, Uwe A1 - Sára, Margit A1 - Hinterdorfer, Peter T1 - Atomic-force-microscopy imaging and molecular-recognition-force microscopy of recrystallized heterotetramers comprising an S-layer-streptavidin fusion protein JF - ChemBioChem KW - Microscopy Y1 - 2018 VL - 7 IS - 4 SP - 588 EP - 591 ER - TY - CHAP A1 - Huber-Gries, Carina A1 - Liu, Jing A1 - Egelseer, Eva-Maria A1 - Rünzler, Dominik A1 - Sára, Margit A1 - Sleytr, Uwe T1 - Application Potential of Bacterial Self-Assembly Systems for Nanobiotechnology T2 - Nanobionics III (from Molecules to Applications) Book of Abstracts KW - Nanotechnology KW - Nanobiology KW - Bacteria Y1 - 2018 ER - TY - JOUR A1 - Saravia, Veronica A1 - Nolte, M. A1 - Huber-Gries, Carina A1 - Puhm, Dietmar A1 - Fery, Andreas A1 - Sleytr, Uwe B. A1 - Toca-Herrera, Jose Luis T1 - Bacterial protein patterning by micro-contact printing of PLL-g-PEG JF - Journal of Biotechnology KW - Proteins Y1 - 2019 IS - 130(3) SP - 247 EP - 252 ER - TY - JOUR A1 - Rünzler, Dominik A1 - Huber-Gries, Carina A1 - Moll, Dieter A1 - Sára, Margit T1 - Biophysical characterization of the entire bacterial surface layer protein SbsB and its two distinct functional domains JF - Journal of Biological Chemistry KW - Life Sciences KW - Protein Y1 - 2019 IS - 279(7) / 13. SP - 5207 EP - 5215 ER - TY - CHAP A1 - Huber-Gries, Carina A1 - Moll, Dieter A1 - Schlegel, Birgit A1 - Rünzler, Dominik A1 - Mader, Christoph A1 - Sára, Margit A1 - Sleytr, Uwe T1 - Recombinant S-layer-streptavidin fursion proteins: Functional protein lattices as nanoarrays for biochip development T2 - Proceedings der 28. Jahrestagung der Österreichischen Gesellschaft für Hygiene, Mikrobiologie und Präventivmedizin, Merano (Italy) KW - Proteins KW - Biochips Y1 - 2019 ER - TY - CHAP A1 - Leeb, Christine A1 - Leitner, Rita A1 - Pichler, Verena A1 - Huber-Gries, Carina A1 - Rünzler, Dominik A1 - Jesenberger, Veronika T1 - Einführung und Optimierung eines praxisorientierten PBL-Moduls im Life-Science-Bereich T2 - Proceedings des Kongresses Problem-Based Learning 2016 PBL - Kompetenzen fördern, Zukunft gestalten KW - Life Science KW - Problem Based Learning KW - Education Y1 - 2018 ER - TY - CHAP A1 - Moll, Dieter A1 - Huber-Gries, Carina A1 - Schlegel, Birgit A1 - Pum, Dietmar A1 - Sleytr, Uwe A1 - Sára, Margit T1 - S-layer-streptavidin fursion protein as template for nanopatterned molecular arrays T2 - Proceedings of the National Academy of Sciences USA KW - Proteins KW - Nanobiology Y1 - 2019 SP - 14646 EP - 14651 ER - TY - GEN A1 - Rünzler, Dominik A1 - Moll, Dieter A1 - Huber-Gries, Carina A1 - Sleytr, Uwe A1 - Sára, Margit A1 - Köhler, Gottfried T1 - Characterization of the Functional Domains of Bacterial Surface Layer Proteins T2 - 5th European Symposium of the Protein Society KW - Proteins Y1 - 2019 ER - TY - GEN A1 - Leeb, Christine A1 - Leitner, Rita A1 - Pichler, Verena A1 - Huber-Gries, Carina A1 - Rünzler, Dominik A1 - Jesenberger, Veronika T1 - Einführung und Optimierung eines praxisorientierten PBL-Moduls im Life-Science-Bereich KW - Life Science KW - Problem Based Learning KW - Education Y1 - 2018 ER - TY - JOUR A1 - Mader, Christoph A1 - Huber-Gries, Carina A1 - Moll, Dieter A1 - Sleytr, Uwe A1 - Sára, Margit T1 - Interaction of the crystalline bacterial cell surface layer protein SbsB and the secondary cell wall polymer of Geobacillus stearothermophilus PV72 assessed by real-time surface plasmon resonance biosensor technology JF - Journal of Bacteriology KW - Bacteria KW - Crystal KW - Protein Y1 - VL - 186 IS - 6 SP - 1758 EP - 1768 ER - TY - GEN A1 - Rünzler, Dominik A1 - Huber-Gries, Carina A1 - Sára, Margit A1 - Köhler, Gottfried T1 - Fluorescence-based Equilibrium and Kinetic Studies on Carbohydrate-Protein Binding: Interaction of Bacterial Surface Layer Proteins with their Specific Secondary Cell Wall Polymers KW - Fluorescence KW - Proteins KW - Polymer Y1 - 2019 ER - TY - CHAP A1 - Huber-Gries, Carina A1 - Moll, Dieter A1 - Liu, Jing A1 - Rünzler, Dominik A1 - Sára, Margit A1 - Sleytr, Uwe B. T1 - Chimaeric S-Layers as Nanopatterned Biomaterials for Applications in Nanobiotechnology T2 - Poster presentation at the 7th Annual Linz Winter Workshop / Book of Abstracts / Linz KW - Biomaterial KW - Nanobiotechnology Y1 - 2019 SP - 1 EP - 10 ER - TY - JOUR A1 - Tang, Jilin A1 - Ebner, Andreas A1 - Ilk, Nicola A1 - Lichtblau, Helga A1 - Huber-Gries, Carina A1 - Zhu, Rong A1 - Pum, Dietmar A1 - Leitner, Michael A1 - Pastushenko, Vassili Filippovich A1 - Gruber, Hermann A1 - Sleytr, Uwe B. A1 - Hinterdorfer, Peter T1 - High-affinity tags fused to s-layer proteins probed by atomic force microscopy JF - Langmuir KW - Proteins Y1 - 2019 IS - 24(4) SP - 1324 EP - 1329 ER - TY - GEN A1 - David, Veronika A1 - Forjan, Mathias A1 - Scherer, Matthias A1 - Reichel, Martin T1 - Entwicklung und Vorstudien zur Implementierung mobiler Rehabilitationssysteme im häuslichen Umfeld KW - Rehabilitation Y1 - ER - TY - JOUR A1 - Tvorogov, Denis A1 - Anisimov, Andrey A1 - Zheng, Wei A1 - Leppánen, Veli-Matti A1 - Tammela, Tuomas A1 - Laurinavicius, Simonas A1 - Holnthoner, Wolfgang A1 - Helotera, Hanna A1 - Holopainen, Tanja A1 - Jeltsch, Michael A1 - Kalkkinen, Nisse A1 - Lankinen, Hikka A1 - Ojala, Päivi M. A1 - Alitalo, Kari T1 - Effective Suppression of Vascular Network Formation by Combination of Antibodies Blocking VEGFR Ligand Binding and Receptor Dimerization JF - Cancer Cell KW - Vascular Network Y1 - 2019 IS - 18(6) SP - 630 EP - 640 ER - TY - GEN A1 - Mühleder, Severin A1 - Fuchs, Christiane A1 - Bassilio, Jose A1 - Sczwarc, Dorota A1 - Pill, Karoline A1 - Slezak, Paul A1 - Labuda, Krystina A1 - Siehs, Christian A1 - Pröll, Johannes A1 - Priglinger, Eleni A1 - Redl, Heinz A1 - Holnthoner, Wolfgang T1 - The purinergic receptor P2Y2 modulates endothelial sprouting and angiogenesis KW - Angiogenesis Y1 - 2018 ER - TY - JOUR A1 - Simsa, Robin A1 - Padma, Arvind A1 - Heher, Philipp A1 - Hellström, Mats A1 - Teuschl, Andreas A1 - Jenndahl, Lachmi A1 - Bergh, Niklas A1 - Fogelstrand, Per T1 - Systematic in vitro comparison of decellularization protocols for blood vessels. JF - PLoS One KW - Tissue Engineering KW - Decellularization KW - Blood Vessel Y1 - ER - TY - JOUR A1 - Nürnberger, S. A1 - Schneider, C. A1 - Keibl, C. A1 - Schädl, Barbara A1 - Heimel, P. A1 - Monforte, X. A1 - Teuschl, A. H. A1 - Nalbach, M. A1 - Thurner, P. J. A1 - Grillari, J. A1 - Redl, Heinz A1 - Wolbank, S. T1 - Repopulation of decellularised articular cartilage by laser-based matrix engraving JF - EBioMedicine. N2 - Background: In spite of advances in the treatment of cartilage defects using cell and scaffold-based therapeutic strategies, the long-term outcome is still not satisfying since clinical scores decline years after treatment. Scaffold materials currently used in clinical settings have shown limitations in providing suitable biomechanical properties and an authentic and protective environment for regenerative cells. To tackle this problem, we developed a scaffold material based on decellularised human articular cartilage. Methods: Human articular cartilage matrix was engraved using a CO2 laser and treated for decellularisation and glycosaminoglycan removal. Characterisation of the resulting scaffold was performed via mechanical testing, DNA and GAG quantification and in vitro cultivation with adipose-derived stromal cells (ASC). Cell vitality, adhesion and chondrogenic differentiation were assessed. An ectopic, unloaded mouse model was used for the assessment of the in vivo performance of the scaffold in combination with ASC and human as well as bovine chondrocytes. The novel scaffold was compared to a commercial collagen type I/III scaffold. Findings: Crossed line engravings of the matrix allowed for a most regular and ubiquitous distribution of cells and chemical as well as enzymatic matrix treatment was performed to increase cell adhesion. The biomechanical characteristics of this novel scaffold that we term CartiScaff were found to be superior to those of commercially available materials. Neo-tissue was integrated excellently into the scaffold matrix and new collagen fibres were guided by the laser incisions towards a vertical alignment, a typical feature of native cartilage important for nutrition and biomechanics. In an ectopic, unloaded in vivo model, chondrocytes and mesenchymal stromal cells differentiated within the incisions despite the lack of growth factors and load, indicating a strong chondrogenic microenvironment within the scaffold incisions. Cells, most noticeably bone marrow-derived cells, were able to repopulate the empty chondrocyte lacunae inside the scaffold matrix. Interpretation: Due to the better load-bearing, its chondrogenic effect and the ability to guide matrix-deposition, CartiScaff is a promising biomaterial to accelerate rehabilitation and to improve long term clinical success of cartilage defect treatment. Funding: Austrian Research Promotion Agency FFG ("CartiScaff" #842455), Lorenz Böhler Fonds (16/13), City of Vienna Competence Team Project Signaltissue (MA23, #18-08). Keywords: Cartilage regeneration; Decellularisation; Ectopic animal model; Laser engraving; Mechanical testing; Repopulation. KW - Tissue Engineering KW - Cartilage regeneration KW - Mechanical Testing KW - Decellularization KW - Biomaterials Y1 - 2021 VL - 64 IS - 103196. ER - TY - JOUR A1 - Schneider, Karl Heinrich A1 - Enayati, Marjan A1 - Grasl, Christian A1 - Walter, Ingrid A1 - Budinsky, Lubos A1 - Zebic, Gabriel A1 - Kaun, Christoph A1 - Wagner, Anja A1 - Kratochwill, Klaus A1 - Redl, Heinz A1 - Teuschl, Andreas A1 - Podesser, Bruno K. A1 - Bergmeister, Helga T1 - Acellular vascular matrix grafts from human placenta chorion: Impact of ECM preservation on graft characteristics, protein composition and in vivo performance. JF - Biomaterials N2 - Small diameter vascular grafts from human placenta, decellularized with either Triton X-100 (Triton) or SDS and crosslinked with heparin were constructed and characterized. Graft biochemical properties, residual DNA, and protein composition were evaluated to compare the effect of the two detergents on graft matrix composition and structural alterations. Biocompatibility was tested in vitro by culturing the grafts with primary human macrophages and in vivo by subcutaneous implantation of graft conduits (n = 7 per group) into the flanks of nude rats. Subsequently, graft performance was evaluated using an aortic implantation model in Sprague Dawley rats (one month, n = 14). In situ graft imaging was performed using MRI angiography. Retrieved specimens were analyzed by electromyography, scanning electron microscopy, histology and immunohistochemistry to evaluate cell migration and the degree of functional tissue remodeling. Both decellularization methods resulted in grafts of excellent biocompatibility in vitro and in vivo, with low immunogenic potential. Proteomic data revealed removal of cytoplasmic proteins with relative enrichment of ECM proteins in decelluarized specimens of both groups. Noteworthy, LC-Mass Spectrometry analysis revealed that 16 proteins were exclusively preserved in Triton decellularized specimens in comparison to SDS-treated specimens. Aortic grafts showed high patency rates, no signs of thrombus formation, aneurysms or rupture. Conduits of both groups revealed tissue-specific cell migration indicative of functional remodeling. This study strongly suggests that decellularized allogenic grafts from the human placenta have the potential to be used as vascular replacement materials. Both detergents produced grafts with low residual immunogenicity and appropriate mechanical properties. Observed differences in graft characteristics due to preservation method had no impact on successful in vivo performance in the rodent model. KW - Biomaterial KW - Tissue Engineering Y1 - SP - 14 EP - 26 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Holnthoner, Wolfgang A1 - Monforte, Xavier T1 - Repopulation of an auricular cartilage scaffold, AuriScaff, perforated with an enzyme combination JF - Acta Biomater. N2 - Biomaterials currently in use for articular cartilage regeneration do not mimic the composition or architecture of hyaline cartilage, leading to the formation of repair tissue with inferior characteristics. In this study we demonstrate the use of "AuriScaff", an enzymatically perforated bovine auricular cartilage scaffold, as a novel biomaterial for repopulation with regenerative cells and for the formation of high-quality hyaline cartilage. AuriScaff features a traversing channel network, generated by selective depletion of elastic fibers, enabling uniform repopulation with therapeutic cells. The complex collagen type II matrix is left intact, as observed by immunohistochemistry, SEM and TEM. The compressive modulus is diminished, but three times higher than in the clinically used collagen type I/III scaffold that served as control. Seeding tests with human articular chondrocytes (hAC) alone and in co-culture with human adipose-derived stromal/stem cells (ASC) confirmed that the network enabled cell migration throughout the scaffold. It also guides collagen alignment along the channels and, due to the generally traverse channel alignment, newly deposited cartilage matrix corresponds with the orientation of collagen within articular cartilage. In an osteochondral plug model, AuriScaff filled the complete defect with compact collagen type II matrix and enabled chondrogenic differentiation inside the channels. Using adult articular chondrocytes from bovine origin (bAC), filling of even deep defects with high-quality hyaline-like cartilage was achieved after 6 weeks in vivo. With its composition and spatial organization, AuriScaff provides an optimal chondrogenic environment for therapeutic cells to treat cartilage defects and is expected to improve long-term outcome by channel-guided repopulation followed by matrix deposition and alignment. STATEMENT OF SIGNIFICANCE: After two decades of tissue engineering for cartilage regeneration, there is still no optimal strategy available to overcome problems such as inconsistent clinical outcome, early and late graft failures. Especially large defects are dependent on biomaterials and their scaffolding, guiding and protective function. Considering the currently used biomaterials, structure and mechanical properties appear to be insufficient to fulfill this task. The novel scaffold developed within this study is the first approach enabling the use of dense cartilage matrix, repopulate it via channels and provide the cells with a compact collagen type II environment. Due to its density, it also provides better mechanical properties than materials currently used in clinics. We therefore think, that the auricular cartilage scaffold (AuriScaff) has a high potential to improve future cartilage regeneration approaches. KW - Auricular cartilage KW - Cartilage Regeneration KW - Human adipose derived stromal/stem cells KW - Tissue Engineering KW - Decellularization Y1 - 2020 VL - 2019 IS - Mar/86 SP - 207 EP - 222 ER - TY - GEN A1 - Rank, Elisabet A1 - Traxler, Lukas A1 - Bayer, Natascha A1 - Reutterer, Bernd A1 - Lux, Kirsten A1 - Drauschke, Andreas T1 - Reproducibility analysis of measurements with a mechanical semiautomatic eye model for evaluation of intraocular lenses KW - Mechanical Eye Y1 - ER - TY - GEN A1 - Obergruber, Julian A1 - Mehnen, Lars T1 - Development of a paraglide control system for automatic pitch stabilization to increase the passive safety KW - Paragliding KW - Safety Y1 - 2018 ER - TY - JOUR A1 - Priglinger, Eleni A1 - Schuh, Christina A1 - Steffenhagen, Carolin A1 - Wurzer, Christoph A1 - Maier, Julia A1 - Nürnberger, Sylvia A1 - Holnthoner, Wolfgang A1 - Fuchs, Christiane A1 - Suessner, Susanne A1 - Rünzler, Dominik A1 - Redl, Heinz A1 - Wolbank, Susanne T1 - Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy. JF - Cytotherapy N2 - BACKGROUND: Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. METHODS: In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. RESULTS: After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. DISCUSSION: Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. KW - Shockwave Therapy KW - Tissue Regeneration KW - Regenerative Medicine Y1 - SP - 1079 EP - 1095 ER - TY - JOUR A1 - Bachmann, Barbara A1 - Spitz, Sarah A1 - Rothbauer, Mario A1 - Jordan, Christian A1 - Purtscher, Michaela A1 - Zirath, Helene A1 - Schuller, Patrick A1 - Eilenberger, Christoph A1 - Ali, Syed Faheem A1 - Mühleder, Severin A1 - Priglinger, Eleni A1 - Harasek, Michael A1 - Redl, Heinz A1 - Holnthoner, Wolfgang A1 - Ertl, Peter T1 - Engineering of three-dimensional pre-vascular networks within fibrin hydrogel constructs by microfluidic control over reciprocal cell signaling JF - Biomicrofluidics KW - Microfluidic KW - Vascularization KW - Tissue Engineering Y1 - 2019 ER - TY - JOUR A1 - Cieślik-Boczula, Katarzyna A1 - Küpcü, Seta A1 - Rünzler, Dominik A1 - Koll, Aleksander A1 - Köhler, Gottfried T1 - Effects of the phenolic lipid 3-pentadecylphenol on phospholipid bilayer organization JF - Journal of Molecular Structure KW - Phospholipid Bilayer Y1 - 2019 IS - 919(1-3) SP - 373 EP - 380 ER - TY - GEN A1 - Schneider, Karl Heinrich A1 - Aigner, Petra A1 - Monforte Vila, Xavier A1 - Holnthoner, Wolfgang A1 - Teuschl, Andreas A1 - Bergmeister, Helga A1 - Redl, Heinz T1 - Naturally derived acellular small diameter vascular grafts from human placenta for reconstructive surgery KW - Placenta KW - Grafting KW - Surgery Y1 - 2018 ER - TY - JOUR A1 - Schneider, Karl A1 - Rohringer, Sabrina A1 - Kapeller, Barbara A1 - Grasl, Christian A1 - Kiss, Herbert A1 - Heber, Stefan A1 - Walter, Ingrid A1 - Teuschl, Andreas A1 - Podesser, Bruno K. A1 - Bergmeister, Helga T1 - Riboflavin-mediated photooxidation to improve the characteristics of decellularized human arterial small diameter vascular grafts JF - Acta Biomater. N2 - Vascular grafts with a diameter of less than 6 mm are made from a variety of materials and techniques to provide alternatives to autologous vascular grafts. Decellularized materials have been proposed as a possible approach to create extracellular matrix (ECM) vascular prostheses as they are naturally derived and inherently support various cell functions. However, these desirable graft characteristics may be limited by alterations of the ECM during the decellularization process leading to decreased biomechanical properties and hemocompatibility. In this study, arteries from the human placenta chorion were decellularized using two distinct detergents (Triton X-100 or SDS), which differently affect ECM ultrastructure. To overcome biomechanical strength loss and collagen fiber exposure after decellularization, riboflavin-mediated UV (RUV) crosslinking was used to uniformly crosslink the collagenous ECM of the grafts. Graft characteristics and biocompatibility with and without RUV crosslinking were studied in vitro and in vivo. RUV-crosslinked ECM grafts showed significantly improved mechanical strength and smoothening of the luminal graft surfaces. Cell seeding using human endothelial cells revealed no cytotoxic effects of the RUV treatment. Short-term aortic implants in rats showed cell migration and differentiation of host cells. Functional graft remodeling was evident in all grafts. Thus, RUV crosslinking is a preferable tool to improve graft characteristics of decellularized matrix conduits. KW - Tissue Engineering KW - Biomaterials KW - Vascularization Y1 - 2021 VL - 2020 IS - 116 SP - 246 EP - 258 ER - TY - JOUR A1 - Schneider, Jaana A1 - Pultar, Marianne A1 - Oesterreicher, Johannes A1 - Bobbili, Madhusudhan Reddy A1 - Mühleder, Severin A1 - Priglinger, Eleni A1 - Redl, Heinz A1 - Spittler, Andreas A1 - Grillari, Johannes A1 - Holnthoner, Wolfgang T1 - Cre mRNA Is Not Transferred by EVs from Endothelial and Adipose-Derived Stromal/Stem Cells during Vascular Network Formation JF - Int J Mol Sci. N2 - Coculture systems employing adipose tissue-derived mesenchymal stromal/stem cells (ASC) and endothelial cells (EC) represent a widely used technique to model vascularization. Within this system, cell-cell communication is crucial for the achievement of functional vascular network formation. Extracellular vesicles (EVs) have recently emerged as key players in cell communication by transferring bioactive molecules between cells. In this study we aimed to address the role of EVs in ASC/EC cocultures by discriminating between cells, which have received functional EV cargo from cells that have not. Therefore, we employed the Cre-loxP system, which is based on donor cells expressing the Cre recombinase, whose mRNA was previously shown to be packaged into EVs and reporter cells containing a construct of floxed dsRed upstream of the eGFP coding sequence. The evaluation of Cre induced color switch in the reporter system via EVs indicated that there is no EV-mediated RNA transmission either between EC themselves or EC and ASC. However, since Cre mRNA was not found present in EVs, it remains unclear if Cre mRNA is generally not packaged into EVs or if EVs are not taken up by the utilized cell types. Our data indicate that this technique may not be applicable to evaluate EV-mediated cell-to-cell communication in an in vitro setting using EC and ASC. Further investigations will require a functional system showing efficient and specific loading of Cre mRNA or protein into EVs. KW - Tissue Engineering KW - Stem Cells KW - Vascular Network Formation KW - EVs KW - Endothelial Cells Y1 - VL - 2021 IS - 22(8) SP - 4050 ER - TY - JOUR A1 - Nürnberger, Sylvia A1 - Schneider, Cornelia A1 - van Osch, Gerjo A1 - Keibl, Claudia A1 - Rieder, Bernhard A1 - Monforte, Xavier A1 - Teuschl, Andreas A1 - Mühleder, Severin A1 - Holnthoner, Wolfgang A1 - Schädl, Barbara A1 - Gahleitner, Christoph A1 - Redl, Heinz A1 - Wolbank, Susanne T1 - Repopulation of an auricular cartilage scaffold, AuriScaff, perforated with an enzyme combination. JF - Acta Biomaterialia KW - Tissue Engineering KW - Decellularization KW - Cartilage Y1 - ER - TY - JOUR A1 - Johannes, Hackethal A1 - Weihs, Anna A1 - Karner, Lisa A1 - Metzger, Magdalena A1 - Dungel, Peter A1 - Hennerbichler, Simone A1 - Redl, Heinz A1 - Teuschl-Woller, Andreas Herbert T1 - Novel Human Placenta-Based Extract for Vascularization Strategies in Tissue Engineering JF - Tissue Eng Part C Methods N2 - There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of two-dimensional (2D) and three-dimensional (3D) in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in native intact tissue. Currently, this issue is only addressed by artificial products such as Matrigel™, which comprises a complex mixture of ECM proteins, extracted from animal tumor tissue. Despite its outstanding bioactivity, the isolation from tumor tissue hinders its translation into clinical applications. Since nonhuman ECM proteins may cause immune reactions, as are frequently observed in clinical trials, human ECM proteins represent the best option when aiming for clinical applications. Here, we describe an effective method of isolating a human placenta substrate (hpS) that induces the spontaneous formation of an interconnected network of green fluorescence-labeled human umbilical vein endothelial cells (gfpHUVECs) in vitro. The substrate was biochemically characterized by using a combination of bicinchoninic acid (BCA) assay, DNA, and glycosaminoglycan (GAG) content assays, sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis and Western blot, angiogenesis arrays, chromatographic thrombin detection, high performance liquid chromatography (HPLC)-based amino acid quantification analysis, and assessment of antimicrobial properties. 2D in vitro cell culture experiments have been performed to determine the vasculogenic potential of hpS, which demonstrated that cell networks developed on hpS show a significantly higher degree of complexity (number of tubules/junctions; total/mean tube length) when compared with Matrigel. As 3D cell culture techniques represent a more accurate representation of the in vivo condition, the substrate was 3D solidified using various natural polymers. 3D in vitro vasculogenesis assays have been performed by seeding gfpHUVECs in an hpS-fibrinogen clot. In conclusion, hpS provides a potent human/material-based alternative to xenogenic-material-based biomaterials for vascularization strategies in tissue engineering. KW - Tissue Engineering KW - Biomaterials KW - HUVEC KW - Acellular biological matrices KW - Angiogenesis and vasculogenesis Y1 - VL - 27 IS - 11 SP - 616 EP - 632 ER - TY - CHAP A1 - Knebl, Gerald A1 - Morton, Tatjana J. A1 - Redl, Heinz A1 - Rünzler, Dominik T1 - Mechanical stimulation of cells in 3-dimensional fibrin constructs using a bioreactor T2 - 3. Forschungsforum der österreichischen Fachhochschulen / Fachhochschule Kärnten KW - Cells KW - Bioreactor Y1 - 2019 SP - 492 EP - 493 ER - TY - JOUR A1 - Schneider, Karl H. A1 - Rohringer, Sabrina A1 - Kapeller, Barbara A1 - Grasl, Christian A1 - Kiss, Herbert A1 - Heber, Stefan A1 - Walter, Ingrid A1 - Teuschl, Andreas H. A1 - Podesser, Bruno K. A1 - Bergmeister, Helga T1 - Riboflavin-mediated photooxidation to improve the characteristics of decellularized human arterial small diameter vascular grafts JF - Acta Biomaterialia N2 - Vascular grafts with a diameter of less than 6 mm are made from a variety of materials and techniques to provide alternatives to autologous vascular grafts. Decellularized materials have been proposed as a possible approach to create extracellular matrix (ECM) vascular prostheses as they are naturally derived and inherently support various cell functions. However, these desirable graft characteristics may be limited by alterations of the ECM during the decellularization process leading to decreased biomechanical properties and hemocompatibility. In this study, arteries from the human placenta chorion were decellularized using two distinct detergents (Triton X-100 or SDS), which differently affect ECM ultrastructure. To overcome biomechanical strength loss and collagen fiber exposure after decellularization, riboflavin-mediated UV (RUV) crosslinking was used to uniformly crosslink the collagenous ECM of the grafts. Graft characteristics and biocompatibility with and without RUV crosslinking were studied in vitro and in vivo. RUV-crosslinked ECM grafts showed significantly improved mechanical strength and smoothening of the luminal graft surfaces. Cell seeding using human endothelial cells revealed no cytotoxic effects of the RUV treatment. Short-term aortic implants in rats showed cell migration and differentiation of host cells. Functional graft remodeling was evident in all grafts. Thus, RUV crosslinking is a preferable tool to improve graft characteristics of decellularized matrix conduits. KW - Tissue Engineering KW - Small diameter vascular graft KW - Biomaterials KW - Decellularization KW - Surface modification Y1 - VL - 116 SP - 246 EP - 258 ER - TY - JOUR A1 - Heinzel, Johannes Christoph A1 - Oberhauser, Viola A1 - Keibl, Claudia A1 - Schädl, Barbara A1 - Swiadek, Nicole V. A1 - Längle, Gregor A1 - Frick, Helen A1 - Slezak, Cyrill A1 - Prahm, Cosima A1 - Grillari, Johannes A1 - Kolbenschlag, Jonas A1 - Hercher, David T1 - ESWT Diminishes Axonal Regeneration following Repair of the Rat Median Nerve with Muscle-In-Vein Conduits but Not after Autologous Nerve Grafting JF - Biomedicines N2 - Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair. KW - Tissue Engineering KW - Muscle-In-Vein Conduits KW - Axonal Regeneration KW - Autologous Nerve Grafting Y1 - VL - 2022 IS - 10(8) SP - 1777 ER - TY - JOUR A1 - Verstraeten, Valerie A1 - Holnthoner, Wolfgang A1 - Van Steensel, Maurice A1 - Veraart, Joep C J M A1 - Bladergroen, Reno S A1 - Heckmann, Caronline A A1 - Keskitalo, Salla A1 - Frank, Jorge A1 - Alitalo, Kari A1 - van Geel, Michel A1 - Steijlen, Peter M T1 - Functional analysis of FLT4 mutations associated with Nonne-Milroy lymphedema JF - Journal of Investigative Dermatology KW - Nonne-Milroy iymphedema KW - Mutation Y1 - 2019 IS - 129(2) SP - 509 EP - 512 ER - TY - JOUR A1 - Holnthoner, Wolfgang T1 - Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction JF - Eur Cell Mater. N2 - The prerequisite for a successful clinical use of autologous adipose-tissue-derived cells is the highest possible regenerative potential of the applied cell population, the stromal vascular fraction (SVF). Current isolation methods depend on high enzyme concentration, lysis buffer, long incubation steps and mechanical stress, resulting in single cell dissociation. The aim of the study was to limit cell manipulation and obtain a derivative comprising therapeutic cells (microtissue-SVF) without dissociation from their natural extracellular matrix, by employing a gentle good manufacturing practice (GMP)-grade isolation. The microtissue-SVF yielded larger numbers of viable cells as compared to the improved standard-SVF, both with low enzyme concentration and minimal dead cell content. It comprised stromal tissue compounds (collagen, glycosaminoglycans, fibroblasts), capillaries and vessel structures (CD31+, smooth muscle actin+). A broad range of cell types was identified by surface-marker characterisation, including mesenchymal, haematopoietic, pericytic, blood and lymphatic vascular and epithelial cells. Subpopulations such as supra-adventitial adipose-derived stromal/stem cells and endothelial progenitor cells were significantly more abundant in the microtissue-SVF, corroborated by significantly higher potency for angiogenic tube-like structure formation in vitro. The microtissue-SVF showed the characteristic phenotype and tri-lineage mesenchymal differentiation potential in vitro and an immunomodulatory and pro-angiogenic secretome. In vivo implantation of the microtissue-SVF combined with fat demonstrated successful graft integration in nude mice. The present study demonstrated a fast and gentle isolation by minor manipulation of liposuction material, achieving a therapeutically relevant cell population with high vascularisation potential and immunomodulatory properties still embedded in a fraction of its original matrix. KW - Adipose-tissue KW - autologous cell therapy KW - microtissue KW - stromal vascular fraction KW - vascularization Y1 - 2020 VL - 2019 IS - Feb, 37 SP - 113 EP - 133 ER - TY - JOUR A1 - Schneider, Karl Heinrich A1 - Aigner, Petra A1 - Holnthoner, Wolfgang A1 - Monforte Vila, Xavier A1 - Nürnberger, Sylvia A1 - Rünzler, Dominik A1 - Redl, Heinz A1 - Teuschl, Andreas T1 - Decellularized human placenta chorion matrix as a favorable source of small-diameter vascular grafts JF - Acta Biomaterialia KW - Grafting KW - Tissue Engineering Y1 - 2018 ER - TY - JOUR A1 - Heimel, Patrick A1 - Swiadek, Nicole V. A1 - Slezak, Paul A1 - Kerbl, Markus A1 - Schneider, Cornelia A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Teuschl, Andreas A1 - Hercher, David T1 - Iodine-Enhanced Micro-CT Imaging of Soft Tissue on the Example of Peripheral Nerve Regeneration JF - Contrast Media & Molecular Imaging KW - µCT KW - Imaging KW - Tissue Engineering KW - Tissue Regeneration Y1 - ER - TY - JOUR A1 - Strohmeier, Karin A1 - Hofmann, Martina A1 - Jacak, Jaroslaw A1 - Narzt, Marie-Sophie A1 - Wahlmueller, Marlene A1 - Mairhofer, Mario A1 - Schädl, Barbara A1 - Holnthoner, Wolfgang A1 - Barsch, Martin A1 - Sandhofer, Matthias A1 - Wolbank, Susanne A1 - Priglinger, Eleni T1 - Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema JF - Biomedicines N2 - Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease. KW - Tissue Engineering KW - Adipose Tissue KW - Lipedema KW - Endothelial Cells Y1 - VL - 2022 IS - 10(5) SP - 1163 ER - TY - JOUR A1 - Rohringer, Sabrina A1 - Holnthoner, Wolfgang A1 - Hackl, Matthias A1 - Weihs, Anna A1 - Rünzler, Dominik A1 - Skalicky, Susanna A1 - Karbiener, Michael A1 - Scheideler, Marcel A1 - Pröll, Johannes A1 - Gabriel, Christian A1 - Schweighofer, Bernhard A1 - Gröger, Marion A1 - Spittler, Andreas A1 - Grillari, Johannes A1 - Redl, Heinz T1 - Molecular and cellular effects of in vitro shockwave treatment on lymphatic endothelial cells. JF - PLoS one KW - Shockwave Y1 - ER - TY - CHAP A1 - Bayer, Natascha A1 - Rank, Elisabet A1 - Traxler, Lukas A1 - Beckert, Erik A1 - Drauschke, Andreas T1 - Implementation of a capsular bag model to enable sufficient lens stabilization within a mechanical eye model T2 - Proc.SPIE 9307, Ophthalmic Technologies XXV KW - Mechanical Eye Y1 - ER - TY - JOUR A1 - Holnthoner, Wolfgang A1 - Szwarc, Dorota T1 - Purinergic P2Y 2 receptors modulate endothelial sprouting JF - Cell Mol Life Sci. N2 - Purinergic P2 receptors are critical regulators of several functions within the vascular system, including platelet aggregation, vascular inflammation, and vascular tone. However, a role for ATP release and P2Y receptor signalling in angiogenesis remains poorly defined. Here, we demonstrate that blood vessel growth is controlled by P2Y2 receptors. Endothelial sprouting and vascular tube formation were significantly dependent on P2Y2 expression and inhibition of P2Y2 using a selective antagonist blocked microvascular network generation. Mechanistically, overexpression of P2Y2 in endothelial cells induced the expression of the proangiogenic molecules CXCR4, CD34, and angiopoietin-2, while expression of VEGFR-2 was decreased. Interestingly, elevated P2Y2 expression caused constitutive phosphorylation of ERK1/2 and VEGFR-2. However, stimulation of cells with the P2Y2 agonist UTP did not influence sprouting unless P2Y2 was constitutively expressed. Finally, inhibition of VEGFR-2 impaired spontaneous vascular network formation induced by P2Y2 overexpression. Our data suggest that P2Y2 receptors have an essential function in angiogenesis, and that P2Y2 receptors present a therapeutic target to regulate blood vessel growth. KW - Angiogenesis KW - Endothelial KW - Purinergic KW - P2Y2 KW - Cell Sprouting Y1 - 2020 VL - 2020 IS - Mar. SP - 885 EP - 901 ER - TY - CHAP A1 - Rank, Elisabet A1 - Traxler, Lukas A1 - Bayer, Natascha A1 - Reutterer, Bernd A1 - Lux, Kirsten A1 - Drauschke, Andreas T1 - Reproducibility analysis of measurements with a mechanical semiautomatic eye model for evaluation of intraocular lenses T2 - Proc.SPIE 8936, Design and Quality for Biomedical Technologies VII KW - Mechanical Eye Y1 - ER - TY - JOUR A1 - Trisko, Johanna A1 - Fleck, Johanna A1 - Kau, Silvio A1 - Oesterreicher, Johannes A1 - Holnthoner, Wolfgang T1 - Lymphatic and Blood Endothelial Extracellular Vesicles: A Story Yet to Be Written JF - Life N2 - Extracellular vesicles (EVs), such as exosomes, microvesicles, and apoptotic bodies, are cell-derived, lipid bilayer-enclosed particles mediating intercellular communication and are therefore vital for transmitting a plethora of biological signals. The vascular endothelium substantially contributes to the circulating particulate secretome, targeting important signaling pathways that affect blood cells and regulate adaptation and plasticity of endothelial cells in a paracrine manner. Different molecular signatures and functional properties of endothelial cells reflect their heterogeneity among different vascular beds and drive current research to understand varying physiological and pathological effects of blood and lymphatic endothelial EVs. Endothelial EVs have been linked to the development and progression of various vascular diseases, thus having the potential to serve as biomarkers and clinical treatment targets. This review aims to provide a brief overview of the human vasculature, the biology of extracellular vesicles, and the current knowledge of endothelium-derived EVs, including their potential role as biomarkers in disease development. KW - Tissue Engineering KW - Endothelial Cells KW - vascularization KW - extracellular vesicles KW - lymphatic endothelial cells Y1 - VL - 2022 IS - 12(5) SP - 654 ER - TY - JOUR A1 - Ferner-Ortner-Bleckmann, Judith A1 - Huber-Gries, Carina A1 - Pavkov-Keller, Tea A1 - Keller, Walter A1 - Mader, Christoph A1 - Ilk, Nicola A1 - Sleytr, Uwe B. A1 - Egelseer, Eva-Maria T1 - The high-molecular-mass amylase (HMMA) of Geobacillus stearothermophilus ATCC 12980 interacts with the cell wall components by virtue of three specific binding regions JF - Molecular Microbiology KW - Cells Y1 - 2019 IS - 72(6) SP - 1448 EP - 1461 ER - TY - GEN A1 - Liousia, Varvara A1 - Salzer, Elias A1 - Mandt, Denise A1 - Rünzler, Dominik T1 - The impact of ethanol in vitro and in vivo: a comparative study KW - In Vivo KW - In Vitro KW - Ethanol Y1 - 2018 ER - TY - JOUR A1 - Ghalamkarpour, A. A1 - Holnthoner, Wolfgang A1 - Saharinen, Pipsa A1 - Boon, Laurence M A1 - Mulliken, J B A1 - Alitalo, Kari T1 - Recessive primary congenital lymphoedema caused by a VEGFR3 mutation JF - Journal of Medical Genetics KW - Lymphoedema Y1 - 2019 IS - 46(6) SP - 399 EP - 404 ER - TY - JOUR A1 - Sayer, Simon A1 - Zandrini, Tommaso A1 - Markovic, Marica A1 - Van Hoorick, Jasper A1 - Van Vlierberghe, Sandra A1 - Baudis, Stefan A1 - Holnthoner, Wolfgang A1 - Ovsianikov, Aleksandr T1 - Guiding cell migration in 3D with high-resolution photografting JF - Scientific Reports N2 - Multi-photon lithography (MPL) has proven to be a suitable tool to precisely control the microenvironment of cells in terms of the biochemical and biophysical properties of the hydrogel matrix. In this work, we present a novel method, based on multi-photon photografting of 4,4′-diazido-2,2′-stilbenedisulfonic acid (DSSA), and its capabilities to induce cell alignment, directional cell migration and endothelial sprouting in a gelatin-based hydrogel matrix. DSSA-photografting allows for the fabrication of complex patterns at a high-resolution and is a biocompatible, universally applicable and straightforward process that is comparably fast. We have demonstrated the preferential orientation of human adipose-derived stem cells (hASCs) in response to a photografted pattern. Co-culture spheroids of hASCs and human umbilical vein endothelial cells (HUVECs) have been utilized to study the directional migration of hASCs into the modified regions. Subsequently, we have highlighted the dependence of endothelial sprouting on the presence of hASCs and demonstrated the potential of photografting to control the direction of the sprouts. MPL-induced DSSA-photografting has been established as a promising method to selectively alter the microenvironment of cells. KW - Tissue Engineering KW - Cell migration KW - photografting Y1 - VL - 2022 IS - 12(1), 10196 SP - 8626 ER - TY - JOUR A1 - Hromada, Carina A1 - Hartmann, Jaana A1 - Oesterreicher, Johannes A1 - Stoiber, Anton A1 - Daerr, Anna A1 - Schädl, Barbara A1 - Priglinger, Eleni A1 - Teuschl-Woller, Andreas H. A1 - Holnthoner, Wolfgang A1 - Heinzel, Johannes Christoph A1 - Hercher, David T1 - Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-Induced Apoptosis of Lymphatic Endothelial Cells In Vitro JF - Biomolecules N2 - Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types' migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC-LEC interaction. KW - Tissue Engineering KW - peripheral nerve regeneration KW - lymphangiogenesis KW - Schwann cells KW - lymphatic endothelial cells Y1 - VL - 2022 IS - 12, 6 SP - 820 ER - TY - JOUR A1 - Lauer, Henrik A1 - Prahm, Cosima A1 - Thiel, Johannes Tobias A1 - Kolbenschlag, Jonas A1 - Daigeler, Adrien A1 - Hercher, David A1 - Heinzel, Johannes Christoph T1 - The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury JF - Biomedicines N2 - The rat median nerve model is a well-established and frequently used model for peripheral nerve injury and repair. The grasping test is the gold-standard to evaluate functional recovery in this model. However, no comprehensive review exists to summarize the course of functional recovery in regard to the lesion type. According to PRISMA-guidelines, research was performed, including the databases PubMed and Web of Science. Groups were: (1) crush injury, (2) transection with end-to-end or with (3) end-to-side coaptation and (4) isogenic or acellular allogenic grafting. Total and respective number, as well as rat strain, type of nerve defect, length of isogenic or acellular allogenic allografts, time at first signs of motor recovery (FSR) and maximal recovery grasping strength (MRGS), were evaluated. In total, 47 articles met the inclusion criteria. Group I showed earliest signs of motor recovery. Slow recovery was observable in group III and in graft length above 25 mm. Isografts recovered faster compared to other grafts. The onset and course of recovery is heavily dependent from the type of nerve injury. The grasping test should be used complementary in addition to other volitional and non-volitional tests. Repetitive examinations should be planned carefully to optimize assessment of valid and reliable data. KW - Tissue Engineering KW - Median Nerve Injury KW - Nerve Regeneration Y1 - VL - 2022 IS - 10(8) SP - 1878 ER - TY - JOUR A1 - Rothbauer, Mario A1 - Byrne, Ruth A. A1 - Schobesberger, Silvia A1 - Olmos Calvo, Isabel A1 - Fischer, Anita A1 - Reihs, Eva I. A1 - Spitz, Sarah A1 - Bachmann, Barbara A1 - Sevelda, Florian A1 - Holinka, Johannes A1 - Holnthoner, Wolfgang A1 - Redl, Heinz A1 - Toegel, Stefan A1 - Windhager, Reinhard A1 - Kiener, Hans P. A1 - Ertl, Peter T1 - Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research JF - Lab on a Chip N2 - Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases. KW - Tissue Engineering KW - coculture joint model KW - arthritis KW - human three-dimensional chip Y1 - VL - 2021 IS - 21 SP - 4128 EP - 4143 ER - TY - GEN A1 - Liousia, Varvara A1 - Rünzler, Dominik T1 - Stage- and dose-dependent effects of methanol and ethanol on the locomotor activity of zebrafish larvae KW - Locomotor Activity KW - Zebrafish Y1 - 2018 ER - TY - JOUR A1 - Kierspel, Thomas A1 - Kadek, Alan A1 - Barran, Perdita A1 - Bellina, Bruno A1 - Bijedic, Adi A1 - Brodmerkel, Maxim N. A1 - Commandeur, Jan A1 - Caleman, Carl A1 - Damjanovic, Tomislav A1 - Dawod, Ibrahim A1 - De Santis, Emiliano A1 - Lekkas, Alexandros A1 - Lorenzen, Kristina A1 - López Morillo, Luis A1 - Mandl, Thomas A1 - Marklund, Erik G. A1 - Papanastasiou, Dimitris A1 - Ramakers, Lennart A. I. A1 - Schweikhard, Lutz A1 - Simke, Florian A1 - Sinelnikova, Anna A1 - Smyrnakis, Athanasios A1 - Timneanu, Nicusor A1 - Uetrecht, Charlotte T1 - Coherent diffractive imaging of proteins and viral capsids: simulating MS SPIDOC JF - Analytical and Bioanalytical Chemistry N2 - MS SPIDOC is a novel sample delivery system designed for single (isolated) particle imaging at X-ray Free-Electron Lasers that is adaptable towards most large-scale facility beamlines. Biological samples can range from small proteins to MDa particles. Following nano-electrospray ionization, ionic samples can be m/z-filtered and structurally separated before being oriented at the interaction zone. Here, we present the simulation package developed alongside this prototype. The first part describes how the front-to-end ion trajectory simulations have been conducted. Highlighted is a quadrant lens; a simple but efficient device that steers the ion beam within the vicinity of the strong DC orientation field in the interaction zone to ensure spatial overlap with the X-rays. The second part focuses on protein orientation and discusses its potential with respect to diffractive imaging methods. Last, coherent diffractive imaging of prototypical T = 1 and T = 3 norovirus capsids is shown. We use realistic experimental parameters from the SPB/SFX instrument at the European XFEL to demonstrate that low- resolution diffractive imaging data (q < 0.3 nm −1 ) can be collected with only a few X-ray pulses. Such low-resolution data are sufficient to distinguish between both symmetries of the capsids, allowing to probe low abundant species in a beam if MS SPIDOC is used as sample delivery. KW - SPI KW - X-ray KW - Native MS KW - Protein complex structure KW - Simulation Y1 - U6 - http://dx.doi.org/https://doi.org/10.1007/s00216-023-04658-y VL - 2023 IS - 415 SP - 4209 EP - 4220 ER - TY - GEN A1 - Friedrich, Robin A1 - Lakic, Nevana A1 - Prähauser, Linda A1 - Schweitzer, Karoline A1 - Olscher, Christoph A1 - Monforte Vila, Xavier A1 - Leitner, Rita A1 - Gepp, Barbara T1 - Effects of Plastic on the Freshwater Snail Biomphalaria Glabrata T2 - SETAC Europe 32nd Annual Meeting in Copenhagen, Denmark from 15 - 19. May 2022 KW - Ecotoxicology KW - Biomphalaria Glabrata Y1 - ER - TY - JOUR A1 - Ashmwe, Mohamed A1 - Posa, Katja A1 - Rührnößl, Alexander A1 - Heinzel, Johannes Christoph A1 - Heimel, Patrick A1 - Mock, Michael A1 - Schädl, Barbara A1 - Keibl, Claudia A1 - Couillard-Despres, Sebastien A1 - Redl, Heinz A1 - Mittermayr, Rainer A1 - Hercher, David T1 - Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats JF - Biomedicines N2 - Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT-applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies. KW - Tissue Engineering KW - ESWT KW - Spinal Cord Injury Y1 - U6 - http://dx.doi.org/https://doi.org/10.3390/biomedicines10071630 VL - 2022 IS - 10(7) SP - 1630 ER -