@article{PurtscherRothbauerKratzetal., author = {Purtscher, Michaela and Rothbauer, Mario and Kratz, Sebastian Rudi Adam and Bailey, Andrew and Lieberzeit, Peter and Ertl, Peter}, title = {A microfluidic impedance-based extended infectivity assay: combining retroviral amplification and cytopathic effect monitoring on a single lab-on-a-chip platform}, series = {Lab on a Chip}, volume = {2021}, journal = {Lab on a Chip}, number = {Issue 7}, pages = {1364 -- 1372}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{BachmannSpitzSchaedletal., author = {Bachmann, Barbara and Spitz, Sarah and Sch{\"a}dl, Barbara and Teuschl, Andreas and Redl, Heinz and N{\"u}rnberger, Sylvia and Ertl, Peter}, title = {Stiffness Matters: Fine-Tuned Hydrogel Elasticity Alters Chondrogenic Redifferentiation}, series = {Froniers in Bioengineering and Biotechnology}, volume = {2020}, journal = {Froniers in Bioengineering and Biotechnology}, number = {8}, pages = {373}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{RosserCalvoSchlageretal., author = {Rosser, Julie and Calvo, Isabel Olmos and Schlager, Magdalena and Purtscher, Michaela and Jenner, Florien and Ertl, Peter}, title = {Recent Advances of Biologically Inspired 3D Microfluidic Hydrogel Cell Culture Systems}, series = {J Cell Biol Cell Metalab}, journal = {J Cell Biol Cell Metalab}, number = {2}, subject = {Hydrogel}, language = {en} } @article{BachmannSpitzRothbaueretal., author = {Bachmann, Barbara and Spitz, Sarah and Rothbauer, Mario and Jordan, Christian and Purtscher, Michaela and Zirath, Helene and Schuller, Patrick and Eilenberger, Christoph and Ali, Syed Faheem and M{\"u}hleder, Severin and Priglinger, Eleni and Harasek, Michael and Redl, Heinz and Holnthoner, Wolfgang and Ertl, Peter}, title = {Engineering of three-dimensional pre-vascular networks within fibrin hydrogel constructs by microfluidic control over reciprocal cell signaling}, series = {Biomicrofluidics}, journal = {Biomicrofluidics}, subject = {Microfluidic}, language = {en} } @article{RothbauerByrneSchobesbergeretal., author = {Rothbauer, Mario and Byrne, Ruth A. and Schobesberger, Silvia and Olmos Calvo, Isabel and Fischer, Anita and Reihs, Eva I. and Spitz, Sarah and Bachmann, Barbara and Sevelda, Florian and Holinka, Johannes and Holnthoner, Wolfgang and Redl, Heinz and Toegel, Stefan and Windhager, Reinhard and Kiener, Hans P. and Ertl, Peter}, title = {Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research}, series = {Lab on a Chip}, volume = {2021}, journal = {Lab on a Chip}, number = {21}, pages = {4128 -- 4143}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} }