@article{WeigelMalkmusWeigeletal.2022, author = {Weigel, Tobias and Malkmus, Christoph and Weigel, Verena and Wußmann, Maximiliane and Berger, Constantin and Brennecke, Julian and Groeber-Becker, Florian and Hansmann, Jan}, title = {Fully Synthetic 3D Fibrous Scaffolds for Stromal Tissues—Replacement of Animal-Derived Scaffold Materials Demonstrated by Multilayered Skin}, series = {Advanced Materials}, volume = {34}, journal = {Advanced Materials}, number = {10}, doi = {10.1002/adma.202106780}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276403}, year = {2022}, abstract = {The extracellular matrix (ECM) of soft tissues in vivo has remarkable biological and structural properties. Thereby, the ECM provides mechanical stability while it still can be rearranged via cellular remodeling during tissue maturation or healing processes. However, modern synthetic alternatives fail to provide these key features among basic properties. Synthetic matrices are usually completely degraded or are inert regarding cellular remodeling. Based on a refined electrospinning process, a method is developed to generate synthetic scaffolds with highly porous fibrous structures and enhanced fiber-to-fiber distances. Since this approach allows for cell migration, matrix remodeling, and ECM synthesis, the scaffold provides an ideal platform for the generation of soft tissue equivalents. Using this matrix, an electrospun-based multilayered skin equivalent composed of a stratified epidermis, a dermal compartment, and a subcutis is able to be generated without the use of animal matrix components. The extension of classical dense electrospun scaffolds with high porosities and motile fibers generates a fully synthetic and defined alternative to collagen-gel-based tissue models and is a promising system for the construction of tissue equivalents as in vitro models or in vivo implants.}, language = {en} } @article{AlHejailanWeigelSchuerleinetal.2022, author = {Al-Hejailan, Reem and Weigel, Tobias and Sch{\"u}rlein, Sebastian and Berger, Constantin and Al-Mohanna, Futwan and Hansmann, Jan}, title = {Decellularization of full heart — optimizing the classical sodium-dodecyl-sulfate-based decellularization protocol}, series = {Bioengineering}, volume = {9}, journal = {Bioengineering}, number = {4}, issn = {2306-5354}, doi = {10.3390/bioengineering9040147}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270781}, year = {2022}, abstract = {Compared to cell therapy, where cells are injected into a defect region, the treatment of heart infarction with cells seeded in a vascularized scaffold bears advantages, such as an immediate nutrient supply or a controllable and persistent localization of cells. For this purpose, decellularized native tissues are a preferable choice as they provide an in vivo-like microenvironment. However, the quality of such scaffolds strongly depends on the decellularization process. Therefore, two protocols based on sodium dodecyl sulfate or sodium deoxycholate were tailored and optimized for the decellularization of a porcine heart. The obtained scaffolds were tested for their applicability to generate vascularized cardiac patches. Decellularization with sodium dodecyl sulfate was found to be more suitable and resulted in scaffolds with a low amount of DNA, a highly preserved extracellular matrix composition, and structure shown by GAG quantification and immunohistochemistry. After seeding human endothelial cells into the vasculature, a coagulation assay demonstrated the functionality of the endothelial cells to minimize the clotting of blood. Human-induced pluripotent-stem-cell-derived cardiomyocytes in co-culture with fibroblasts and mesenchymal stem cells transferred the scaffold into a vascularized cardiac patch spontaneously contracting with a frequency of 25.61 ± 5.99 beats/min for over 16 weeks. The customized decellularization protocol based on sodium dodecyl sulfate renders a step towards a preclinical evaluation of the scaffolds.}, language = {en} } @article{SchwedhelmZdziebloAppeltMenzeletal.2019, author = {Schwedhelm, Ivo and Zdzieblo, Daniela and Appelt-Menzel, Antje and Berger, Constantin and Schmitz, Tobias and Schuldt, Bernhard and Franke, Andre and M{\"u}ller, Franz-Josef and Pless, Ole and Schwarz, Thomas and Wiedemann, Philipp and Walles, Heike and Hansmann, Jan}, title = {Automated real-time monitoring of human pluripotent stem cell aggregation in stirred tank reactors}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-48814-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202649}, pages = {12297}, year = {2019}, abstract = {The culture of human induced pluripotent stem cells (hiPSCs) at large scale becomes feasible with the aid of scalable suspension setups in continuously stirred tank reactors (CSTRs). Innovative monitoring options and emerging automated process control strategies allow for the necessary highly defined culture conditions. Next to standard process characteristics such as oxygen consumption, pH, and metabolite turnover, a reproducible and steady formation of hiPSC aggregates is vital for process scalability. In this regard, we developed a hiPSC-specific suspension culture unit consisting of a fully monitored CSTR system integrated into a custom-designed and fully automated incubator. As a step towards cost-effective hiPSC suspension culture and to pave the way for flexibility at a large scale, we constructed and utilized tailored miniature CSTRs that are largely made from three-dimensional (3D) printed polylactic acid (PLA) filament, which is a low-cost material used in fused deposition modelling. Further, the monitoring tool for hiPSC suspension cultures utilizes in situ microscopic imaging to visualize hiPSC aggregation in real-time to a statistically significant degree while omitting the need for time-intensive sampling. Suitability of our culture unit, especially concerning the developed hiPSC-specific CSTR system, was proven by demonstrating pluripotency of CSTR-cultured hiPSCs at RNA (including PluriTest) and protein level.}, language = {en} }