锂基生物陶瓷葡聚糖水凝胶调控脂肪浸润型肩袖修复及其机制研究

The treatment of fatty infiltration of rotator cuff injury is biomechanically strengthening the connection between the rotator cuff tendon and the humeral head, but the surgical technique did not promote osseo-integration between them and did not solve the problem of fatty infiltration. We found that calcium phosphate ceramic can promote the bone regeneration in interface of tendon to bone and change the weak link, but can not inhibit rotator cuff with fatty infiltration. There are several reports that lithium can promote mesenchymal stem cells (MSCs) osteogenic differentiation and inhibit adipogenic differentiation. We hypothesis that biological ceramics doped with lithium salt can inhibit the rotator cuff fatty infiltration and promote tendon to bone integration, reducing postoperative retear rate. In order to verify this hypothesis, the lithium salt and bioceramic composite lithium bioceramics, and dextran glycidyl methacrylate is synthesized cross-linked dextran based hydrogels, and then synthesize lithium based injectable bioactive ceramics; In vitro experimental, study the mechanism of the composite scaffold promoting MSCs osteogenic differentiation and inhibiting adipogenic differentiation; In rats model with the fatty infiltration of rotator cuff injury, we inject composite scaffold to rotator cuff tendon and the humeral head, evaluate the quality of the humeral head and rotator cuff local tissue injury from the aspect of gross, histology, molecular biology and biomechanics, providing a new method for the treatment of rotator cuff injury with fatty infiltration.

目前伴有脂肪浸润陈旧性肩袖损伤的治疗是靠手术生物力学加强肩袖肌腱端与肱骨头之间连接，没有增进两者之间骨性整合，更没有解决伴发的脂肪浸润问题。我们研究发现磷酸钙陶瓷可促进腱骨界面骨内生，改变了常规修复形成的薄弱连接，却不能抑制脂肪浸润。同时有报道锂盐既可促进间充质干细胞（MSCs）向成骨分化又可抑制成脂分化。据此提出假说：生物陶瓷掺杂锂盐可抑制肩袖脂肪浸润，促进肌腱-骨骨性整合，降低术后再撕裂率。为了验证这一假说，拟将锂盐与生物陶瓷复合锂盐生物陶瓷，葡聚糖和甲基丙烯酸缩水甘油酯合成可交联葡聚糖基水凝胶，再将两者合成可注射锂基生物陶瓷；体外实验研究该复合支架对MSCs具有成骨抑脂分化影响及其作用机制；采用伴有脂肪浸润的陈旧性肩袖损伤大鼠模型，术中注射复合支架，从大体、组织学、分子生物学及生物力学等角度，评估提高袖肱骨头复合体局部组织质量效果，为伴有脂肪浸润陈旧性肩袖损伤提供一种新的治疗方法。

目前伴有脂肪浸润陈旧性肩袖损伤的治疗是靠手术生物力学加强肩袖肌腱端与肱骨头之间连接，没有增进两者之间骨性整合，更没有解决伴发的脂肪浸润问题。有报道锂盐既可促进间充质干细胞（MSCs）向成骨分化又可抑制成脂分化。据此提出假设：锂盐可同时抑制肩袖脂肪浸润及促进肌腱-骨界面的骨性整合，降低术后再撕裂率。本研究将锂盐与介孔硅纳米颗粒（MSNs）相结合，并采用电纺技术打造稳定性调控体系，克服手术治疗的局限性，为伴有脂肪浸润的陈旧性肩袖损伤的治疗提供新思路。同时在肩袖损伤术后腱骨愈合方面，本课题还聚焦于从腱到骨的渐层功能结构，建立一系列肩袖补片，旨在完成重建腱骨界面矿物渐变结构和纤维软骨结构以及巨大肩袖缺损的修复。