精确激活整合素信号支架的构建及其指导骨修复中 H 型血管新生机制研究

快速引导损伤区域中血管网络重建并建立充足的血流灌注依然是骨组织再生领域面临的重要挑战。H型血管由于高携氧性、高通透性及其高效介导前体成骨细胞分化的能力在血管化骨再生领域受到广泛关注。然而，如何利用生物材料本身的理化特性调控组织微环境中宿主细胞的行为及相关信号诱导H型血管新生尚且未知。现有研究表明骨发育过程中整合素信号对H型血管的形成至关重要。基于此，本项目拟利用生物工程构建纤连蛋白突变多肽，旨在通过精确激活宿主内皮细胞整合素的表达诱导骨修复中H型血管的形成，多维度考察其对周边宿主细胞的调控作用。另外，本项目将比较植入材料激活不同整合素信号介导治疗性血管新生的差异，并重点阐明该材料调控H型血管新生的规律及作用机制。本项目研究将为新型骨修复材料的设计与制备提供新的思路。

Rapid promotion of vascular network reconstruction to re-establish adequate perfusion in the injured area remains a major challenge so far for bone regeneration. Recently, Type H vessel has attracted extensive attention in the vascularized bone regeneration due to its properties of high oxygenation and permeability, which has been associated with osteogenesis. However, it is still unknown how biomaterial itself regulating the behavior and signaling of host cells to induce the formation of Type H vessels. Emerging study suggest that the integrin signaling is crucial for the formation of Type H vessels during bone development. Based on this, this project intends to construct mutant peptide from fibronectin to precisely activate the expression of integrin in host endothelial cells to induce the formation of Type H vessels during bone repair, and further to investigate its regulatory effect on surrounding host cells in multiple dimensions. Additionally, this project will utilize the prepared implants to activate different integrins and compare their differences in inducing therapeutic angiogenesis, and elucidate the mechanisms of how the implants regulating the formation of Type H vessels. This research will provide new insights for the design and preparation of novel bone repair materials.