Aberle Timo, Franke Katrin, Rist Elke, Benz Karin, Schlosshauer Burkhard
Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Reutlingen, Germany.
PLoS One. 2014 Jan 27;9(1):e86740. doi: 10.1371/journal.pone.0086740. eCollection 2014.
In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin) to generate a blend (technical term: quattroGel), an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.
在再生医学领域，我们旨在开发满足特定组织需求的植入基质。通过将两种本身具有细胞相容性的凝胶系统与酶交联剂（明胶/转谷氨酰胺酶和纤维蛋白原/凝血酶）相结合，生成一种混合物（技术术语：四元凝胶），意外地产生了细胞选择性。四元凝胶具有多孔性，在细胞直径范围内形成空洞，具有分钟级的凝胶化动力学、粘弹性以及适合一般细胞黏附的机械强度，并限制扩散。内皮细胞、软骨细胞和成纤维细胞的细胞增殖基本不受影响。相比之下，在内皮细胞在四元凝胶上既不形成血管管，原代神经元也不会大量延伸神经突。仅从胶原蛋白异构体表达判断，只有软骨细胞能正常分化。四元凝胶的生物物理特性似乎使有丝分裂等不同细胞过程不受影响，有利于固着细胞的分化，但阻碍迁移细胞的分化。这种细胞类型选择性在例如关节软骨或椎间盘修复过程中具有重要意义，在这些过程中，病理性神经支配和血管生成在组织工程中代表着不良事件。
