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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 -