bFGF和BMP-2序贯释放对牙周组织再生的影响

以干细胞移植为基础的传统牙周组织工程是修复牙周缺损的重要方向，但要转化为临床应用尚存在障碍。动员足量的自身功能细胞迁移到缺损区，并适时定向分化，重建牙周组织成为新的策略。我们前期研究发现bFGF能促进细胞增殖、趋化和干性维持，BMP-2能促进成骨分化。因而采用bFGF和BMP-2联合应用并序贯释放可以实现对干细胞功能的综合调控：在创伤愈合早期释放bFGF，募集干细胞到达创伤局部，并发挥促增殖、干性维持和血管神经再生的作用；而后在细胞增殖高峰期，释放BMP-2，促进干细胞定向成骨/成牙骨质分化，可以有效促进牙周再生。据此，本项目拟通过体外实验探讨两者联合对牙周膜干细胞增殖、趋化、干性维持和成骨分化的影响；构建共载bFGF和BMP-2的温敏凝胶序贯控释体系，并通过体内实验研究两者序贯释放对干细胞动员、定向分化及牙周组织再生的协同促进效应。这一策略有望为牙周病的治疗提供新的思路和方法。

Stem cell transplantation-based traditional periodontal tissue engineering is one important direction of regeneration and reconstruction of periodontal defect. However, many barriers limit its clinical application. Recruitment of enough endogenous functional cells to the defect regions and promotion of their committed differentiation at appropriate times to reestablish the destroyed periodontium becomes a new strategy for periodontal regeneration. Our previous study found that bFGF could promote the proliferation, chemotaxis and maintain the stemness of bone marrow stromal cells (BMSCs) while BMP-2 enhanced osteogenic differentiation. Therefore, the combination and sequential timed-release of bFGF and BMP-2 can comprehensively regulate stem cell function. Firstly, the controlled and sustained system can release bFGF at the early stage of wound healing to recruit stem cells to the wound area, and promote the proliferation and maintain the stemness of stem cells, as well as enhance angiogenesis and neuranagenesis. Afterwards, at the peak period of proliferation, BMP-2 will be released and enhance the osteogenic/cementogenic differentiation of stem cells, therefore to promote periodontal regeneration. In this grant, we propose to investigate the combined effects of bFGF and BMP-2 on the proliferation, chemotaxis, stemness and osteogenic differentiation of periodontal ligament stem cells. Moreover, we will construct co-delivery thermosensitive hydrogel system for the sequential timed-release of bFGF and BMP-2. Finally, rat periodontal defect will be created to explore the effects and mechanisms of bFGF and BMP-2 sequential release on the recruitment, committed differentiation and periodontal regeneration in vivo. This strategy will help to create a new insight into the clinical therapy of periodontal diseases and provide scientific foundation for the successful application of in situ tissue engineering technique in periodontal tissue regeneration.