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 - 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 -