新型自愈性水凝胶对于股骨头坏死的疗效及其机制研究

The pathogenesis of osteonecrosis of femoral head (ONFH) remains elusive and thus leads to a lack of effective intervention approach. Due to their osteogenic capacity, bone marrow stem cells (BMSCs) were considered to play an important part in the development of ONFH, as well as in the treatment for early-staged ONFH. In our previous studies, we found significant changes in transcriptome in BMSCs in ONFH, resulting in the impairment of cellular function. Further, we improved the properties of silk-fibroin hydrogel, and made it injectable, and used it for bone regeneration of irregular bone defect. According to our results, we assumed that CaP@mSF hydrogel could repair the necrotic lesion through improving osteogenic capacity of BMSCs by altering the expression of transcriptome. In the research, we intend to made intensive study in the molecular mechanisms of CaP@mSF hydrogel in the treatment for early ONFH and find theoretic base for further advances in the efficiency of CaP@mSF hydrogel for the treatment for ONFH.

股骨头坏死（ONFH）发病机制不明，缺乏有效的早期干预措施。骨髓间充质干细胞（BMSC）具有较好的成骨功能，被认为在ONFH发生发展及治疗中具有重要作用。课题组前期研究发现，ONFH中BMSC转录组表达发生明显变化，导致细胞功能受损。我们改进了丝蛋白（SF）水凝胶的性能，使其可进行深部注射并通过BMSC修复不规则骨缺损。基于以上实验结果，我们推测，CaP@mSF水凝胶可能通过改变ONFH坏死区域局部的BMSC基因及转录组表达，改善BMSC细胞功能，促进ONFH坏死区域的修复。本课题旨在通过体外细胞培养及动物体内实验，深入探究新型CaP@mSF水凝胶治疗早期ONFH的分子机制，为进一步改进CaP@mSF水凝胶对于早期股骨头坏死的疗效打下理论基础。

股骨头坏死好发于中青年人群，病因包括大量使用糖皮质激素、长期酗酒、创伤等。股骨头坏死(ONFH)发病机制不明，缺乏有效的早期干预措施。课题组前期研究发现，股骨头坏死患者的BMSC转录组表达发生明显变化，在股骨头坏死的发生发展中发挥重要作用。前期实验发现可注射丝蛋白(SF)水凝胶可填充修复不规则骨缺损。本课题旨在通过体外细胞培养及动物体内实验，深入探究新型磷酸钙丝蛋白水凝胶治疗早期股骨头坏死的体内外成骨性能和安全性。首先通过转录组测序对比分析，运用生物信息学方法分析激素性股骨头坏死患者和对照组患者（发育性股骨头发育不良）BMSCs间差异表达的miRNA和circRNA，进一步通过免疫荧光、qPCR、染色、WB等方法观察其相互调控及其在BMSCs成骨、成脂分化中的作用，进一步改进可长期负载ncRNA的磷酸钙丝蛋白水凝胶材料，分别在细胞和动物水平观察缓释ncRNA水凝胶材料的安全性和骨修复性能。