增强增韧型多孔磷酸钙植入体协同PRP凝胶促进骨组织再生与重建

The porous calcium phosphate ceramic was toughened and strengthened by in situ growth whisker structure, and the collagen hydrogel with encapsulated Platelet Rich Plasma (PRP) was perfused into toughened and strengthened porous calcium phosphate ceramic to build novel bone defect restoration implant by aseptic freeze-drying. This implant could simultaneously guarantee osteoinduction and mechanical properties by optimizing 3D pore structural design, the whisker toughening and reinforcing and micro/nano- structure of materials. The porous collagen structure within freeze-drying novel bone defect restoration implant could effectively adsorb and recruit of bone marrow mesenchymal stem cells (MSCs) deriving from the bone defect by physical absorption and material induced characteristic. The released PRP from collagen hydrogel, which could stimulate and mobilize the body's natural repairment and regeneration process by large amounts of active factor, and further accelerated the recruitment and osteoblast differentiation of MSCs, and promoted the integration of implant-bone defect interface and accelerated bone defect repair. After the novel implant was built in the bone defect site, the full integration and collaboration of the holistic and perfect bone prosthesis implant among material, cells and growth factor was assembled by utilizing PRP as growth factor, MSCs as seed cells and osteoinduction toughening and reinforcing porous calcium phosphate ceramic as tissue scaffold, which would provide more innovative and practical perspective for the clinical application of regenerative medicine materials.

本项目以多孔磷酸钙陶瓷为基体，通过原位生长晶须结构，制备晶须增强增韧型多孔磷酸钙，将复合富血小板血浆（PRP）的胶原基水凝胶灌注到增强增韧型多孔磷酸钙中，冷冻干燥构建新型骨修复植入体。该类植入体通过材料的三维孔结构优化设计、晶须的补强增韧及其微纳米结构同时保证其诱导能力和力学强度。通过胶原水凝胶在体内有效吸附和募集骨髓间充质干细胞(MSCs)，利用缓释的PRP中富含大量活性因子特性激发并调动机体的自然修复和再生过程，同时进一步加速MSCs的募集和成骨分化，促进植入体-骨缺损界面的整合，完成骨性愈合。因此，可通过新型植入体在体内的协同效应，同时利用PRP（生长因子）和骨髓间充质干细胞（种子细胞），结合具有骨诱导能力的多孔磷酸钙陶瓷，构建出材料-细胞-生长因子有机结合的全效骨修复植入体，为未来骨科再生医学材料的临床应用提供新的发展方向。

由骨质疏松、肿瘤、运动和交通事故等带来的骨创伤和骨缺损已成为影响人类生命健康的重大问题，对骨修复材料的需求也在持续高速增长，寻求一种理想的骨移植替代材料是骨生物材料领域的研究热点。.本项目一方面以多孔磷酸钙陶瓷为基体，通过原位生长晶须结构，制备晶须增强增韧型多孔磷酸钙；另一方面以胶原基生物材料为基础，构建了各类水凝胶材料，并引入磷酸钙无机相、PRP等弥补胶原自身功能的不足。然后通过材料学设计将功能化胶原基水凝胶系列材料和磷酸钙陶瓷材料有机复合，构建了不同新型骨修复植入体支架。.研究结果表明，制备出的增强增韧型多孔磷酸钙孔隙丰富，孔间贯通性好，孔壁上生成的晶须和灌注的纳米颗粒形成了较稳定的“钢筋-混凝土”型微纳米结构，在保证力学强度不变的情况下仍具有较高的孔隙率，能够促进BMSCs的增殖和成骨分化。与纯胶原水凝胶相比，加入PRP后的生物活性水凝胶在促进BMSCs的粘附，增殖和成骨分化方面具有显著的优势。复合PRP的胶原水凝胶能够加速和增强骨修复效果。通过羟基磷灰石浆料引入水凝胶进行功能增强后，水凝胶孔隙结构未发生显著变化的同时，复合水凝胶的机械性能和稳定性均得到大幅度提高。陶瓷基材和水凝胶复合后，多孔支架表面的水凝胶层一方面可以作为复合支架的保护层，另一方面磷酸钙基材所释放的钙离子还能对成骨起到促进作用。细胞实验表明复合支架能够促进干细胞的富集、迁移，有利于原位的骨和血管生成。动物实验结果表明复合支架与宿主周围环境具有良好的骨整合作用，缺损区X射线密度更接近正常颅骨，有大量新骨形成。复合支架通过募集内源性干细胞快速启动骨缺损处的血管生成和新骨再生，有效促进骨重建。.通过本项目的开展，成功构建出材料、细胞、生长因子有机结合的全链条骨修复植入体，激发并调动机体的自然修复和再生过程，促进材料-骨界面的有效整合，加速骨缺损修复，实现缺损部位的骨再生和重建，对骨再生医学的发展具有一定价值。