掺锶硅酸钙/丝蛋白负载脂肪干细胞促进颌骨缺损功能重建研究

Achieving rapid osteogenesis and angiogenesis for jaw defects was the key factor for maxillofacial bone regeneration and follow-up functional reconstruction. The silk fibroin material with good mechanical properties can be used as scaffold for bone repair, but its lack activities of osteogenesis and angiogenesis cannot realize functional reconstruction of jaw defects. Recently, our newly research revealed that the strontium-substituted calcium silicate bioceramics possess enhanced activities on osteogenesis and angiogenesis. Present study intends to construct strontium-substituted calcium silicate/silk fibroin composite materials with bidirectional inducing activities of osteogenesis and angiogenesis via combining the functional components of strontium-substituted calcium silicate and silk fibroin. Then, the regulatory effects and related mechanisms of the novel composite materials on osteogenic and angiogenic differentiation of adipose-derived stem cells will be systematically explored. Moreover, adipose-derived stem cells will be loaded on the new composite materials to construct vascularized tissue-engineered bone. Then, the in vivo effects of osteogenesis, angiogenesis, and osseointegration with dental implants will be evaluated in rat mandible defects and canine mandible defects with implant placement. The present study plays an important theoretic and applied role in the design of the scaffold materials, which could promote rapid osteogenesis and angiogenesis for jaw defects. Moreover, the vascularized tissue-engineered bone constructed with the composite materials and adipose-derived stem cells may provide a new method and strategy for functional reconstruction of jaw defects, which possesses important scientific significance and clinical applications.

实现颌骨缺损快速成骨及血管化是颌面部骨再生及其后续功能修复重建的关键。丝蛋白材料具有良好力学性能可作为骨修复支架材料，但其缺乏诱导成骨和成血管活性而无法实现颌骨缺损功能重建。课题组新近研究发现掺锶硅酸钙生物陶瓷具有优越的促成骨和成血管活性。本项目拟将掺锶硅酸钙与丝蛋白复合以构建具有成骨/成血管双向诱导活性的掺锶硅酸钙/丝蛋白复合支架材料,研究该复合支架材料对脂肪干细胞成骨/成血管的调控作用与机理；并以此新型复合支架材料负载脂肪干细胞构建血管化组织工程骨，应用于大鼠颌骨缺损及犬颌骨块状缺损牙种植动物模型，评价体内成骨、成血管及种植体骨整合效果。本项目的实施将为实现促颌骨缺损快速成骨及血管化的支架材料的设计奠定基础，并复合脂肪干细胞构建血管化组织工程骨，从而为颌骨缺损功能性修复提供新的方法及策略，具有重要的科学意义和临床应用价值。

实现颌骨缺损快速成骨及血管化是颌面部骨再生及其后续功能修复重建的关键。丝蛋白材料具有良好力学性能可作为骨修复支架材料，但其缺乏诱导成骨和成血管活性而无法实现颌骨缺损功能重建。在课题组前期研究及预实验基础上，本项目成功制备新型掺锶硅酸钙/丝蛋白材料体系；证明其具有成骨/成血管双向诱导活性；其对大鼠脂肪干细胞的成骨/成血管作用与AKT、p38及ERK信号通路相关，且三条信号通路间可能存在交联作用。此外，课题组将此新型复合支架材料应用于大鼠颅骨缺损动物模型，证实其具有良好的体内骨修复效果；另以其负载脂肪干细胞构建血管化组织工程骨，应用于大鼠颌骨缺损动物模型，研究其承受咬合力的同时体内颌骨成骨/成血管效果。依托本项目，课题组发表SCI论文3篇，中文核心期刊论文2篇；参加国内外学术会议3次，并发表会议论文3篇；组织项目组成员出国合作交流1次；培养硕士研究生3名，博士研究生1名。本项目的实施为实现促颌骨缺损快速成骨及血管化的支架材料的设计奠定基础，并复合脂肪干细胞构建血管化组织工程骨，从而为颌骨缺损功能性修复提供新的方法及策略，具有重要的科学意义和临床应用价值。