缓释凋亡小体的功能化双相纳米纤维膜通过调控内质网钙通道蛋白TMCO1促进牙周炎组织修复的机制研究

慢性牙周炎常导致牙周膜干细胞成骨分化功能损伤。恢复炎性损伤牙周膜干细胞成骨分化功能对于提高临床牙周炎组织再生治疗效果极其重要。针对该问题，本项目利用界面诱导自组装技术，将含有干细胞来源凋亡小体的多肽水凝胶涂层结合在前期研发的仿生纳米羟基磷灰石/聚己内酯复合纳米纤维表面，构建一种缓释凋亡小体的功能化双相纳米纤维膜用于引导牙周组织再生治疗，以期通过靶向缓释凋亡小体，调控牙周膜干细胞的内质网钙离子通道蛋白TMCO1，抑制成骨分化关键转录因子Runx2的泛素化降解，进而恢复炎性损伤牙周膜干细胞的成骨分化功能，促进牙周炎组织的再生修复。本项目将在细胞和分子水平明确TMCO1作为炎性损伤牙周膜干细胞潜在治疗靶点的价值，同时进一步探讨凋亡小体调控炎性损伤牙周膜干细胞成骨分化功能的分子机制。本项目有望为牙周炎组织再生修复治疗提供新思路和综合治疗策略。

Chronic inflammation usually damages the osteogenic differentiation capability of periodontal ligament stem cells in periodontitis (P-PDLSCs). Rescuing the osteogenic differentiation capability of the injured P-PDLSCs is crucial to the reconstruction of damaged periodontal tissue in periodontitis. To address this issue, a functionalized biphasic nanofiber membrane will be developed for guided periodontal tissue regeneration in this project by loading the peptide hydrogel layer which contains stem cells-derived apoptotic bodies on the biomimetic apatite reinforced polycaprolactone composite nanofibers via surface-induced hydrogelation. It is hypothesized that the controlled released apoptotic bodies from materials could inhibit the ubiquitin-mediated degradation of Runx2, which is the key transcription factor during osteogenic differentiation of stem cells, and further rescue the osteogenic differentiation capability of the injured P-PDLSCs through the regulation of transmembrane and coiled-coil domains 1 (TMCO1), a Ca2+ leak channel in endoplasmic reticulum, eventually promoting the repair of periodontal tissue in periodontitis. To prove this hypothesis, the role of TMCO1 in P-PDLSCs will be determined in our project. Moreover, the detailed regulatory mechanism of apoptotic body on the osteogenic differentiation of P-PDLSCs will be explored at cellular and molecular levels. It is believed that our project will provide an enlightening insight into the strategies of periodontal regeneration treatment for patients with periodontitis.