BMP2/VEGF双基因活化可注射互穿网络水凝胶的构建及其在骨组织再生中的应用

Maxillary posterior bone deficiency has been a bottleneck to restrict the success of dental implant, and the maxillary sinus floor elevation is a classical method to solve this problem. According to the irregular anatomical characteristics of the maxillary sinus, based on previous work, our group prepared an injectable interpenetrating network hydrogel as bone tissue engineering scaffold, silk fibroin / mesoporous bioactive glass / sodium alginate (SF/MBG/SA)，and optimized the gel time and mechanical properties suitable for the actual needs of the clinical operation. The polymer/pDNA complexes were made of plasmid bone morphogenetic protein -2 or plasmid vascular endothelial growth factor with linoleic acid modified polyethyleneimine, and the polymer/pDNA complexes were mixed with SF/MBG/SA hydrogel. Furthermore, we evaluated the in vitro biological properties of this double gene activated hydrogels. And then this double gene activated hydrogels were used in the study of the rabbit maxillary sinus lifting and canine maxillary sinus elevation with simultaneous implant restoration to evaluate its in vivo osteogenic angiogenesis and osseointegration effect. The double gene activaed interpenetrating network hydrogel is expected to become a safe, efficient and minimally invasive method for the maxillary sinus lifting and other irregular lacunar bone defects because which compound the advantages of injectable biomaterials and non viral gene therapy.

上颌后牙区种植骨量不足一直是制约牙种植术成功的瓶颈，上颌窦底提升术是解决这一难题的经典方法。针对上颌窦腔隙不规则的解剖特点，课题组在前期工作的基础上，利用介孔生物活性玻璃(MBG)的可调节性成骨/成血管潜能，基于丝蛋白(SF)与海藻酸钠(SA)溶液的凝胶化机理，在酸性分子的调节促进作用下，制备SF/MBG/SA互穿网络凝胶体系并优化其凝胶时间及力学性能以适宜临床操作的实际需求；然后以PEI-LA介导质粒BMP-2和VEGF复合SF/MBG/SA，研究BMP2/VEGF-SF/MBG/SA双基因活化水凝胶的体外生物学性能，评价其在兔上颌窦提升和犬上颌窦提升同期种植修复中的成骨成血管和骨整合效果。该双基因活化水凝胶结合可注射型生物材料、非病毒基因治疗的优势，将进一步促进新骨血管化，加快咀嚼等口腔功能重建，可望为上颌窦提升种植修复及其他不规则腔隙性骨缺损修复提供一种安全、高效、微创的新方法。

上颌后牙区种植骨量不足一直是制约牙种植术成功的瓶颈，上颌窦底提升术是解决这一难题的经典方法。针对上颌窦腔隙不规则的解剖特点，本项目利用介孔生物活性玻璃(MBG)的可调节性成骨/成血管潜能，基于丝蛋白(SF)与海藻酸钠(SA)溶液的凝胶化机理，在酸性分子维生素C的调节促进作用下，成功制备SF/MBG/SA互穿网络凝胶体系，进一步优化其凝胶时间及力学性能以适宜临床操作的实际需求。基于阳离子聚合物载体PEI-LA负载BMP2/VEGF的SF/MBG/SA互穿网络水凝胶对干细胞成骨诱导分化和成血管诱导分化能力的影响有限，及SF/MBG/SA互穿网络凝胶体系中的无机纳米颗粒可作为活性因子(如鸢尾素i因子等)的载体，我们进一步构建了氧化石墨烯（GO）及明胶还原氧化石墨烯（GOG）纳米颗粒载体，并将其用于BMP-2短肽（P24）或香草酸甲酯（MV）的负载和控释，实现对干细胞的诱导分化作用；负载i因子或GO-P24的复合水凝胶材料能够显著促进动物体内成骨，验证了其作为不规则腔隙性骨缺损修复缓释材料的可行性。本项目执行期间，发表第一标注本项目论文1篇，发表第六标注本项目SCI论文3篇；参与培养硕士研究生1名、博士研究生1名。已完成计划任务书的各项考核指标。