新型蚕丝支架复合间质细胞衍生因子（SDF-1）促进前交叉韧带修复再生的效能和机制研究

Anterior cruciate ligament (ACL) is frequently ruptured during sports and other rigorous physical activities, and ofen fails to heal optimally due to the lack of ideal grafts. Our group have developed an effective tendon tissue-engineering graft with knitted silk and collagen sponge(Biomaterials 2010). However,due to the complicated structure and poor regeneration ability of ACL, its use in ACL repair still remains two challenge: dys-heal of bone tunnel and the lack of seed cells in articular cavity. Our group also have found that SDF-1 can selectively increase the recruitment of cells to improve tendon repair(Cell Transplant 2012). Based on these results, we try to develop a neotype combined silk scaffold(bone-ligament-bone scaffold), simultaneously, by incorporation of bioactive SDF-1, to enable selective migration and homing of cells for in situ ACL regeneration. The purpose of current project is to explore the mechanism of SDF-1's selective attraction; understand the regulation effect of different material surface for bone/ligament differentiation; evaluate the regeneration effect of combined scaffold with SDF-1 for ACL repair. Our project not only develop an effective tissue-engineering silk scaffold for the regeneration of ACL, but also explore the mechanism of SDF-1 regulation, thus provide expirical study basis for the clinical treatment of ACL injury.

前交叉韧带（ACL）损伤是较常见的运动损伤，缺乏理想替代物，严重影响膝关节功能。本课题组前期研究发现蚕丝-胶原支架是一种有效的肌腱组织工程支架(Biomaterials2010），但其用于结构复杂且再生困难的ACL重建还存在两个挑战：骨隧道愈合不良和关节腔内种子细胞缺乏。另外，本课题组也发现SDF-1可选择性引导细胞迁移促肌腱修复(Cell Transplant2012）。所以本研究根据ACL的复合解剖结构构建了一种新型骨-腱-骨复合蚕丝支架（纳米羟基磷灰石-蚕丝-胶原支架），并复合具有调节干细胞迁移能力的SDF-1促进其重建。本课题探讨SDF-1选择性吸引细胞迁移的机制；明晰不同材料界面调控骨/韧带分化的效应；运用组织工程手段在动物体内评估SDF-1复合支架促进ACL修复的效能。通过此课题，将获得一种新型ACL支架，探索SDF-1作用机理，并为ACL的临床治疗新手段开发提供实验研究基础。

肌腱/韧带损伤是临床常见运动系统损伤之一。目前的传统治疗手段尚无法达到令人满意的临床疗效，尤其是对那些强度要求较高的高水平竞技运动员。本研究基于前期发现蚕丝-胶原支架是一种有效的肌腱组织工程支架，SDF-1可选择性引导细胞迁移促肌腱修复。所以本研究通过构建SDF-1缓释蚕丝胶原支架，分离获取前交叉韧带来源干细胞，运用组织工程手段在动物体内评估 SDF-1缓释蚕丝胶原支架复合关节腔细胞注射促进 ACL 修复的效能。本研究发现1、前交叉韧带组织内存在一群具有干性特性的细胞 2、SDF-1缓释蚕丝胶原支架有效促进注射细胞向支架靶向迁移和存活 3、SDF-1缓释蚕丝胶原支架联合关节腔细胞注射早期减少了炎症反应，6个月后重建韧带具有一定的波浪结构，且腱骨愈合处可见骨隧道外侧隧道闭合。本研究通过SDF-1缓释蚕丝胶原支架联合关节腔细胞注射同时促进韧带再生和腱骨愈合，一种趋化因子缓释支架联合关节腔注射技术的新策略对临床ACL重建提供了新的思路。