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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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, 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 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 - 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 - 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 - TY - JOUR A1 - Hanetseder, Dominik A1 - Levstek, Tina A1 - Teuschl-Woller, Andreas A1 - Frank, Julia Katharina A1 - Schaedl, Barbara A1 - Redl, Heinz A1 - Marolt Presen, Darja T1 - Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age JF - Front Bioeng Biotechnol N2 - Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing. KW - aging KW - iPSCs KW - osteogenic differentiation KW - bone marrow stromal cells KW - extracellular matrix Y1 - U6 - http://dx.doi.org/https://doi.org/10.3389/fbioe.2023.1214019 VL - 11 ER - TY - JOUR A1 - Bernhard, Jonathan C A1 - Marolt Presen, Darja A1 - Li, Ming A1 - Monforte, Xavier A1 - Ferguson, James A1 - Leinfellner, Gabriele A1 - Heimel, Patrick A1 - Betti, Susanne L A1 - Shu, Sharon A1 - Teuschl-Woller, Andreas H A1 - Tangl, Stefan A1 - Redl, Heinz A1 - Vunjak-Novakovic, Gordana T1 - Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts JF - Cells N2 - Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks. The pathways' constructs were evaluated over time with respect to gene expression, composition, histomorphology, microstructure, vascularization and biomechanics. Hypertrophic chondrocytes expressed higher levels of osteogenic genes and deposited significantly more bone mineral and proteins than the osteoblasts. Before implantation, the mineral in the hyper group was less mature than that in the osteo group. Following 12 weeks of implantation, the hyper group had increased mineral density but a similar overall mineral composition compared with the osteo group. The hyper group also displayed significantly more blood vessel infiltration than the osteo group. Both groups contained M2 macrophages, indicating bone regeneration. These data suggest that, similar to the body's repair processes, endochondral pathway might be more advantageous when regenerating large defects, whereas intramembranous ossification could be utilized to guide the tissue formation pattern with a scaffold architecture. KW - bone tissue engineering KW - endochondral KW - mesenchymal stromal cells KW - ossification KW - intramembranous Y1 - U6 - http://dx.doi.org/10.3390/cells11193070 VL - 11 IS - 19:3070 ER - TY - JOUR A1 - Feichtinger, Xaver A1 - Heimel, Patrick A1 - Tangl, Stefan A1 - Keibl, Claudia A1 - Nürnberger, Sylvia A1 - Schanda, Jakob Emanuel A1 - Hercher, David A1 - Kocijan, Roland A1 - Redl, Heinz A1 - Grillari, Johannes A1 - Fialka, Christian A1 - Mittermayr, Rainer T1 - Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture JF - PLoS One KW - chronic rotator cuff repair KW - bone microarchitecture Y1 - U6 - http://dx.doi.org/10.1371/journal.pone.0262294 VL - 17 IS - 1 ER -