仿生光交联凝胶调控整合素αvβ6-TGF-β轴促进脂肪基质细胞修复椎间盘的效应及机制研究

椎间盘退变所致的慢性下腰痛是一个全球性的健康问题，尽管有许多针对椎间盘修复的组织工程研究，但至今没有找到理想的方法。我们在前期发现光交联的明胶丙烯酸甲酯水凝胶可以促进软骨细胞外基质再生的基础上，构建了一种新型的仿椎间盘生物力学性能的光交联水凝胶，并复合脂肪基质细胞（ASC）对结构与功能更为复杂的椎间盘进行修复研究，取得了初步的结果，但其分子机制与修复效应并不清晰。本课题拟通过探讨不同力学性能的光交联水凝胶对ASC分化的影响，优化理想材料的制备；阐明光交联水凝胶通过调控整合素αvβ6-TGF-β轴促进ASC向髓核样分化的机制；运用组织工程手段在动物体内评价优化水凝胶复合ASC修复椎间盘的效能。最终为水凝胶结合ASC修复椎间盘退变的生物学治疗提供理论基础。

Intervertebral disc degeneration (IVDD) has caused major social burden worldwide. Although there are many tissue engineering studies for intervertebral disc repair, the ideal method has not been found so far. Our previous study show that the photocrosslinked gelatin methacrylate hydrogel can promote the regeneration of extracellular matrix of chondrocytes. Based on this finding, we construct a novel photocrosslinked hydrogel with the biomechanical properties of the intervertebral discs. We combine this hydrogel with the adipose stromal cells (ASC) on the intervertebral disc repair study, and achieve preliminary results, but its molecular mechanism and repair effect is not clear. In this study, we will investigate the effect of photocrosslinked hydrogel with different mechanical properties on the differentiation of ASC, and optimize the preparation of ideal hydrogel. Furthermore, we will analysis the mechanism of photo-crosslinked hydrogel in ASC differentiation by regulating the integrin αvβ6-TGF-β axis. Finally, we will investigate the therapeutic effect of combining photo-crosslinked hydrogel and ASC in vivo. Our study will provide a theoretical foundation for treating IVDD with photo-crosslinked hydrogel and ASC.