Abstract：
Limited bone regeneration, uncontrollable degradation rate, mismatched defect zone and poor operability have plagued the reconstruction of irregular bone defect by tissue-engineered materials. A combination of biomimetic scaffolds with hydroxyapatite has gained great popularity in promoting bone regeneration. Therefore, we designed an injectable, photocurable and in-situ curing hydrogel by methacrylic anhydride -modified carboxymethyl cellulose (CMC-MA) loading with spherical hydroxyapatite (HA) to highly simulate the natural bony matrix and match any shape of damaged tissue. The prepared carboxymethyl cellulose-methacrylate/ hydroxyapatite(CMC-MA/HA) composite presented good rheological behavior, swelling ratio and mechanical property under light illumination. Meanwhile, this composite hydrogel promoted effectively proliferation, supported adhesion and upregulated the osteogenic-related genes expression of MC3T3-E1 cells in vitro, as well as the activity of the osteogenic critical protein, Integrin α1, β1, Myosin 9, Myosin 10, BMP-2 and Smad 1 in Integrin/BMP-2 signal pathway. Together, the composite hydrogels realized promotion of bone regeneration, deformity improvement, and the enhanced new bone strength in skull defect. It also displayed a good histocompatibility and stability of subcutaneous implantation in vivo. Overall, this study laid the groundwork for future research into developing a novel biomaterial and a minimally invasive therapeutic strategies for reconstructing bone defects and contour deficiencies.
摘要：
有限的骨再生，不可控的降解速率，缺损区不匹配和可操作性差困扰着组织工程材料重建不规则骨缺损。仿生支架与羟基磷灰石的组合在促进骨再生方面已获得极大的普及。因此,我们设计了一种注射剂，通过甲基丙烯酸酐改性的羧甲基纤维素（CMC-MA）负载球形羟基磷灰石（HA），可光固化和原位固化水凝胶，以高度模拟天然骨基质并匹配任何形状的受损组织。制备的羧甲基纤维素-甲基丙烯酸酯/羟基磷灰石(CMC-MA/HA)复合材料具有良好的流变性能,光照下的溶胀率和力学性能。同时,这种复合水凝胶有效促进增殖，在体外支持MC3T3-E1细胞的粘附并上调成骨相关基因的表达，以及成骨关键蛋白的活性，整合素α1、β1、肌球蛋白9、肌球蛋白10、BMP-2和Smad1参与整合素/BMP-2信号通路。一起,复合水凝胶实现了骨再生的促进作用，畸形改善，和增强颅骨缺损的新骨强度。它还显示了良好的组织相容性和体内皮下植入的稳定性。总的来说,这项研究为未来研究开发新型生物材料和重建骨缺损和轮廓缺陷的微创治疗策略奠定了基础。
