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 - 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 - 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 -