组织工程骨目前临床应用受限的瓶颈是难以实现高度血管化，而体内的骨血管化形成是多种细胞、生长因子及细胞外基质共同介导、协同作用的结果。为此，本项目首先设计一类兼有良好的力学性能、可调控的降解速率、易于高度血管化的微/纳纤维相互“贯穿”的改性甲壳素晶须增强聚乳酸/壳聚糖复合多孔支架；然后，高度利用贻贝足丝蛋白中的粘结分子--多巴胺的超强粘附性，将促血管和骨组织形成的关键性生长因子、细胞和蛋白（VEGF、EPCs、BMP-9、CD34+、Connexin-43蛋白、RGD短肽等）快速、有效地单一或协同固定到复合多孔支架表面。通过生物力学微环境下的细胞共培养和体内植入实验，研究多种生物活性分子单一作用或协同引导对材料表面的细胞响应行为、血管化和骨组织形成的影响规律，重点探明多种生物活性分子内在的协同作用，阐明它们之间的相互作用机制及信号通道。为血管化组织工程骨的构建与临床应用提供参考与科学依据。

The bottleneck for the clinical application of tissue engineered bone at present is lake of high densities blood vessels, while the angiogenesis of bone in vivo is the results of the synergic effect of a variety of cells, growth factors and extracellular matrix. In this project, chitin whiskers reinforced poly (lactic acid)/chitosan composite porous scaffold with micro-nano fiber interpenetrating structure, good mechanical performance, controllable degradation rate and high specific surface area for vascularization was firstly obtained. Then, a variety of key growth factors, cell and proteins for vascularization and bone formation, such as VEGF、EPCs、BMP-9、CD34+、Connexin-43、RGD, have been immobilized on the surfaces of the composite porous scaffold based on the mussel protein—dopamine. The singular and synergic effects of the bioactive molecules on the cell response behavior, vascularization and bone formation are studied, and the interaction mechanism and signal channel of the bioactive molecules were clarified too. The findings of this project will supply experiment data and scientific support for the preparation of vascularized tissue engineering bone and its application in clinical practices.