骨髓间充质干细胞（BMSCs）在植入体骨整合中起着至关重要的作用。BMSCs具有多向分化潜能，如向成骨方向分化则有利于骨整合。植入体表面的形貌、结构和化学信号可以转导为BMSCs内特定的分子信号，诱导BMSCs向成骨方向分化。本项目拟在钛植入体表面可控制备不同Sr、Zn负载量的SrTiO3、ZnTiO3纳米管阵列，模拟细胞外基质纳米环境，同时原位释放促进BMSCs成骨分化的微量元素Sr和Zn，二者协同作用有效地诱导BMSCs成骨分化；观察BMSCs在SrTiO3、ZnTiO3纳米管阵列表面形态及成骨标志物的基因表达情况，研究纳米管结构及微量元素（Sr、Zn）对BMSCs成骨分化的影响；通过体内外实验研究SrTiO3、ZnTiO3纳米管阵列诱导BMSCs成骨分化相关的信号分子及其相互关系，揭示其诱导BMSCs成骨分化的内在细胞分子机制。本研究对设计新型高成骨活性骨植入材料具有重要的理论意义。

Bone mesenchymal stem cells (BMSCs) play a crucial role in bone regeneration and bony fixation of implanted biomaterials. Most of the osteoblastic cells that colonize the implant surface to induce bone growth originate from BMSCs, and hence, in order to accomplish good osseointegration, it is critical to induce the differentiation of BMSCs preferentially toward osteogenitor cells and then into osteoblasts in lieu of other cell lineages. Recent studies revealed some key molecules and signaling pathways could be potential targets for modulation of BMSCs commitment to the bone lineage. Better understanding of the molecular mechanisms and signaling pathways of BMSCs commitment to the bone lineage on the biomedical implants will help to design and fabricate bioactive implant to optimize therapeutic strategy for accelerating wound healing, damage repair and regeneration. Titanium (Ti) and Ti alloys which have lower elastic moduli, high strength and excellent corrosion resistance are widely used in orthopedic surgery and dentistry. In this project, bioactive SrTiO3 or ZnTiO3 nanotubular coating that could mimic environment of extracellular matrix of natural bone and in-situ deliver Zn or Sr will be fabricated on Ti implants to induce the BMSCs commitment to the bone lineage. The morphology of adhered BMSCs and gene expression of biochemical markers of osteoblast and bone formation will be investigated. The molecular mechanisms and intracellular signaling molecule pathways for BMSCs commitment to the osteoblast lineage on SrTiO3 or ZnTiO3 nanotubular coating will be identified and their intrinsic biomolecular mechanism will be revealed. This project will provide substantial fundament for designing and developing new biocompatible materials to regulation of the signaling pathways and extracellular matrix of BMSCs commitment to the osteoblast lineage to enhance osteoblasts activities and osseointegration, which have important scientific significance and great economic benefits.

骨髓间充质干细胞（BMSCs）具有多向分化潜能，如向成骨方向分化则有利于骨结合的形成。植入体表面的结构和化学信号可以转导为BMSCs内特定的分子信号，诱导BMSCs向成骨方向分化。本项目在钛种植体表面可控制备不同Sr、Zn负载量的SrTiO3、ZnTiO3纳米管阵列，模拟细胞外基质纳米环境，同时原位释放促进BMSCs成骨分化的微量元素Sr和Zn，有效地诱导BMSCs成骨分化。通过控制阳极化的电压和水热反应的时间，实现了SrTiO3、ZnTiO3纳米管阵列管径和Sr、Zn释放量的可控。具有纳米管阵列表面的钛植入体与纯钛相比具有更好的细胞粘附合铺展能力，纳米管阵列负载Sr、Zn后BMSCs在植入体表面能充分伸展，体现出成骨细胞的多边形形态，有利于向成骨细胞分化，促进骨生成。成骨相关基因在纯Ti及TiO2、SrTiO3纳米管阵列表面的表达情况也不同， SrTiO3纳米管中成骨标志物 (RUNX2、ALP、OCN、BMP-2、Col-1) mRNA表达明显要比TiO2纳米管中要高，这一结果这次表明SrTiO3纳米管阵列与纯TiO2纳米管阵列相比更能够促进BMSCs向成骨方向分化。通过光化学还原，在SrTiO3纳米管阵列管内沉积具有光谱抗菌能力的纳米Ag颗粒，在钛植入体表面得到了Sr、Ag共载的纳米管阵列，实现了同时提高植入体的骨整合性能和抗菌性能。本项目为开发新型具有良好生物活性和靶向定位促进骨创伤愈合的新型骨植入体材料，提供了新的思路和研究基础，具有重要的科学意义和应用价值。本项目。本项目已在SCI期刊上发表论文3篇，培养硕士研究生2人，项目负责人在国内外学术会议上作口头报告2次。