功能化三维生物活性玻璃多孔支架诱导内源性骨再生

Currently, trauma, tumor resection, infection and congenital malformations caused large bone defects remains a significant unmet clinical challenge. Scaffold-mediated neovascularization and endogenous bone regeneration is promising alternative to conventional autologous graft for repair of large bone defect. In this proposal, desferoxamine (DFO) is introduced into 3D bioactive glass porous scaffolds (BG) due to its simulate hypoxia function and is applied to endogenous bone regeneration. Firstly, DFO is chemically crosslinked with gelatin (Gel) to decrease its toxicity and extend its half-life, and Gel-DFO is coated on BG scaffolds through dip coating method; Secondly, the scaffold’s in vitro toxicity, its influence on the expression of VEGF and SDF-1 as well as the mechanism are studied; Thirdly, mice skull defects is used to study the effect of scaffolds on the neovascularization and endogenous bone regeneration. The aim of this proposal is preparing a new 3D porous scaffold, which can simulate the hypoxic response, thereby activating HIF-1, increasing the expression of VEGF and SDF-1, effectively promoting neovascularization and homing stem cells, promoting endogenous bone regeneration, finally providing new alternative materials for large bone defect healing.

目前由创伤、肿瘤切除、感染和先天畸形引起的大块骨缺损的修复是临床面临的一大挑战。支架介导的内源性骨再生是替代传统自体骨移植修复大面积骨缺损的有效手段。本研究拟利用去铁胺(DFO)模拟低氧反应的功能，将DFO引入三维生物活性玻璃(BG)多孔支架，诱导内源性骨再生。主要研究：1) DFO经由化学键结合到明胶(Gel)上，降低DFO的毒性，延长血管内半衰期，并通过溶液浸涂的方式将Gel-DFO涂层到三维支架上；2) 体外细胞评价三维支架的毒性及其对细胞VEGF、SDF-1表达的影响，并阐明其诱导机制；3) 体内小鼠颅骨缺损实验评价三维支架对新生血管及内源性骨再生的作用。本项目旨在构建一种新型的具备模拟低氧功能的三维多孔支架，能够提高HIF-1的稳定性，诱导VEGF和SDF-1因子的表达，有效地促进新生血管和干细胞的归巢，促进内源性骨再生的功能，为临床大面积骨缺损修复提供新的替代材料。

目前由创伤、肿瘤切除、感染和先天畸形引起的大块骨缺损的修复是临床面临的一大挑战。支架介导的内源性骨再生是替代传统自体骨移植修复大面积骨缺损的有效手段。本研究拟利用去铁胺(DFO)模拟低氧反应的功能，将DFO引入三维生物活性玻璃-硅酸锂镁(BG-XLS)多孔支架。主要研究：1) DFO与甲基丙烯酰化明胶(GelMA)共混，滴涂到BG-XLS支架上，并通过紫外光交联GelMA，降低DFO的毒性，延长血管内半衰期；2)体外细胞评价三维支架的毒性及其对细胞VEGF表达的影响；3) 体内大鼠颅骨缺损实验评价三维支架对内源性骨再生的作用。本项目旨在构建一种新型的具备模拟低氧功能的三维多孔支架，能够提高HIF-1的稳定性，诱导VEGF因子的表达，有效地促进血管新生/血管形成和干细胞的归巢，促进内源性骨再生的功能，为临床大块骨缺损修复提供新的替代材料。