TY - JOUR A1 - Mandl, Thomas A1 - Meyerspeer, Martin A1 - Reichel, Martin A1 - Kern, Helmut A1 - Hofer, Christian A1 - Mayr, Winfried A1 - Moser, Ewald T1 - Functional electrical stimulation of long-term denervated, degenerated human skeletal muscle: estimating activation using T2-parameter magnetic resonance imaging methods JF - Artif Organs KW - Electrical Stimulation KW - Muscle Stimulation Y1 - 2019 IS - 32(8) SP - 604 EP - 608 ER - 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 - CHAP A1 - Mally, Franziska A1 - Hofstätter, Otto A1 - Eckelt, Markus T1 - Influence of Running Shoes and Running Velocity on “Ride” during Running. T2 - ISEA 2020 Online - Proceedings 2020 KW - Sports Equipment Technologies KW - Running Shoes KW - Footwear Y1 - 2020 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 - Meyer, Markus A1 - Donsa, Klaus A1 - Truskaller, Thomas A1 - Frohner, Matthias A1 - Pohn, Birgit A1 - Felfernig, Alexander A1 - Sinner, Franz A1 - Pieber, Thomas T1 - Development of a Protocol for Automated Glucose Measurement Transmission Used in Clinical Decision Support Systems Based on the Continua Design Guidelines T2 - Conference Proceedings eHealth 2018 KW - Mobile Health KW - Standardization KW - Clinical Decision Support Systems KW - Diabetes KW - Medication Errors Y1 - ER - TY - GEN A1 - Meyer, Markus A1 - Donsa, Klaus A1 - Truskaller, Thomas A1 - Frohner, Matthias A1 - Pohn, Birgit A1 - Felfernig, Alexander A1 - Sinner, Franz A1 - Pieber, Thomas T1 - Development of a Protocol for Automated Glucose Measurement Transmission Used in Clinical Decision Support Systems Based on the Continua Design Guidelines KW - Mobile Health KW - Standardization KW - Clinical Decision Support Systems KW - Diabetes KW - Medication Errors Y1 - ER - TY - GEN A1 - Mandl, Thomas A1 - Dohnal, Fahdi A1 - Stickler, Yvonne A1 - Martinek, Johannes A1 - Reichel, Martin A1 - Mayr, Winfried A1 - Rattay, Frank T1 - FE-Modellierung für Implantate als Alternative zur transkutanen Elektrostimulation des langzeitdenervierten Oberschenkels KW - Implants KW - Denervation Y1 - 2019 ER - TY - GEN A1 - Kornfeind, P. A1 - Blaha, A. A1 - Peuschl, M. A1 - Reichel, Martin A1 - Sabo, Anton T1 - 2-Komponentenplattform zur Erfassung der Stemmbrettkräfte am Ruderergometer und im Ruderboot KW - Sport KW - Rowing Y1 - 2019 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 - Mally, Franziska T1 - In-Shoe Plantar Pressure Measurement—Influence of Insole Placement on Selected Parameters during Running. T2 - ISEA 2020 Online - Proceedings 2020, 49(1) KW - Sports Equipment Technologies KW - Running Shoes KW - Motion Analysis Y1 - 2020 SP - 50 EP - 50 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 - Frohner, Matthias A1 - Mense, Alexander A1 - Krondraf, Nikolaus A1 - Sabutsch, Stefan T1 - Implementierungsleitfaden HL7 Implementation Guide for CDA® R2: Implementierungsleitfaden Meldung an das Epidemiologische Meldesystem (EMS) – Labor-und Arztmeldung, ELGA GmbH JF - ELGA CDA Implementierungsleitfäden HL7 KW - eHealth KW - ELGA Y1 - VL - 2020 ER - TY - JOUR A1 - Frohner, Matthias A1 - Sabutsch, Stefan A1 - Krondraf, Nikolaus T1 - ELGA CDA Implementierungsleitfäden HL7 Implementation Guide for CDA® R2: Ambulanzbefund, ELGA GmbH JF - ELGA CDA Implementierungsleitfäden HL7 KW - eHealth KW - ELGA Y1 - VL - 2020 ER - TY - CHAP A1 - Eckelt, Markus A1 - Mally, Franziska T1 - Running Shoes—Possible Correlations of Biomechanical and Material Tests. T2 - ISEA 2020 Online - Proceedings 2020, 49(1) KW - Sports Equipment Technologies KW - Running Shoes Y1 - 2020 SP - 25 EP - 25 ER - TY - CHAP A1 - Eckelt, Markus A1 - Mally, Franziska T1 - Use of Acceleration Sensors in Archery T2 - ISEA 2020 Online - Proceedings 2020, 49(1) KW - Sports Equipment Technologies KW - Acceleration Sensors KW - Archery Y1 - 2020 SP - 98 EP - 98 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 - Bayer, Natascha T1 - Intraocular lens measurement setup based on a mechanical eye model KW - Eye Model KW - Intraocular Lens KW - Cataract 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 -