TY - JOUR A1 - Al-Hejailan, Reem A1 - Weigel, Tobias A1 - Schürlein, Sebastian A1 - Berger, Constantin A1 - Al-Mohanna, Futwan A1 - Hansmann, Jan T1 - Decellularization of full heart — optimizing the classical sodium-dodecyl-sulfate-based decellularization protocol JF - Bioengineering N2 - 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. KW - tissue engineering KW - decellularization KW - vascularized scaffold KW - cardiac patch KW - dynamic culture Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270781 SN - 2306-5354 VL - 9 IS - 4 ER - TY - JOUR A1 - Weigel, Tobias A1 - Schmitz, Tobias A1 - Pfister, Tobias A1 - Gaetzner, Sabine A1 - Jannasch, Maren A1 - Al-Hijailan, Reem A1 - Schürlein, Sebastian A1 - Suliman, Salwa A1 - Mustafa, Kamal A1 - Hansmann, Jan T1 - A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro JF - Scientific Reports N2 - Pacemaker systems are an essential tool for the treatment of cardiovascular diseases. However, the immune system’s natural response to a foreign body results in the encapsulation of a pacemaker electrode and an impaired energy efficiency by increasing the excitation threshold. The integration of the electrode into the tissue is affected by implant properties such as size, mechanical flexibility, shape, and dimensionality. Three-dimensional, tissue-like electrode scaffolds render an alternative to currently used planar metal electrodes. Based on a modified electrospinning process and a high temperature treatment, a conductive, porous fiber scaffold was fabricated. The electrical and immunological properties of this 3D electrode were compared to 2D TiN electrodes. An increased surface of the fiber electrode compared to the planar 2D electrode, showed an enhanced electrical performance. Moreover, the migration of cells into the 3D construct was observed and a lower inflammatory response was induced. After early and late in vivo host response evaluation subcutaneously, the 3D fiber scaffold showed no adverse foreign body response. By embedding the 3D fiber scaffold in human cardiomyocytes, a tissue-electrode hybrid was generated that facilitates a high regenerative capacity and a low risk of fibrosis. This hybrid was implanted onto a spontaneously beating, tissue-engineered human cardiac patch to investigate if a seamless electronic-tissue interface is generated. The fusion of this hybrid electrode with a cardiac patch resulted in a mechanical stable and electrical excitable unit. Thereby, the feasibility of a seamless tissue-electrode interface was proven. KW - biomedical materials KW - cardiac device therapy KW - hybrid pacemaker Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177368 VL - 8 IS - 14545 ER - TY - JOUR A1 - Moll, Corinna A1 - Reboredo, Jenny A1 - Schwarz, Thomas A1 - Appelt, Antje A1 - Schürlein, Sebastian A1 - Walles, Heike A1 - Nietzer, Sarah T1 - Tissue Engineering of a Human 3D in vitro Tumor Test System JF - Journal of Visualized Experiments N2 - Cancer is one of the leading causes of death worldwide. Current therapeutic strategies are predominantly developed in 2D culture systems, which inadequately reflect physiological conditions in vivo. Biological 3D matrices provide cells an environment in which cells can self-organize, allowing the study of tissue organization and cell differentiation. Such scaffolds can be seeded with a mixture of different cell types to study direct 3D cell-cell-interactions. To mimic the 3D complexity of cancer tumors, our group has developed a 3D in vitro tumor test system. Our 3D tissue test system models the in vivo situation of malignant peripheral nerve sheath tumors (MPNSTs), which we established with our decellularized porcine jejunal segment derived biological vascularized scaffold (BioVaSc). In our model, we reseeded a modified BioVaSc matrix with primary fibroblasts, microvascular endothelial cells (mvECs) and the S462 tumor cell line For static culture, the vascular structure of the BioVaSc is removed and the remaining scaffold is cut open on one side (Small Intestinal Submucosa SIS-Muc). The resulting matrix is then fixed between two metal rings (cell crowns). Another option is to culture the cell-seeded SIS-Muc in a flow bioreactor system that exposes the cells to shear stress. Here, the bioreactor is connected to a peristaltic pump in a self-constructed incubator. A computer regulates the arterial oxygen and nutrient supply via parameters such as blood pressure, temperature, and flow rate. This setup allows for a dynamic culture with either pressure-regulated pulsatile or constant flow. In this study, we could successfully establish both a static and dynamic 3D culture system for MPNSTs. The ability to model cancer tumors in a more natural 3D environment will enable the discovery, testing, and validation of future pharmaceuticals in a human-like model. KW - bioengineering KW - biomedical engineering KW - tissue engineering KW - biotechnology KW - cultured KW - tumor cells KW - cell culture KW - 3D in vitro models KW - bioreactor KW - dynamic culture conditions KW - tumor test system KW - primary cell isolation KW - BioVaSc KW - decellularization KW - equipment and supplies KW - cellular microenvironment KW - culture techniques KW - cell engineering KW - anatomy KW - physiology KW - molecular biology KW - cellular biology Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132277 UR - http://www.jove.com/video/50460 VL - 78 IS - e50460 ER -