超声示踪载药PLGA/Lipid复合纳泡修饰的BMSCs及其调控修复骨质疏松性骨损伤的研究

干细胞移植技术在骨修复治疗领域具有巨大应用潜力，而干细胞的在体归巢示踪、定向分化调控及成骨重塑优化是该技术中亟待解决的问题。我们前期已成功研制出可超声成像及载药控释的新型PLGA/Lipid复合多孔缓释纳泡，初步证实其可被骨髓间充质干细胞（BMSCs）摄取并保持良好的超声成像性能。BMP-2活性肽P24具有诱导干细胞定向分化为成骨细胞的性能，我们的工作进一步证实载P24支架材料可较好的促进骨缺损修复。巴多昔芬（BZA）可激活成骨细胞核内的雌激素受体促进骨重塑进而改善骨质量。本项目拟借助PLGA/Lipid纳泡负载P24与BZA，通过胞内携载该纳泡评估BMSCs归巢的超声示踪性能，研究纳泡内药物的超声可控性释放及其对BMSCs成骨分化的调控，探讨超声干预下BZA/P24-PLGA/Lipid纳泡修饰BMSCs对骨质疏松性骨损伤的修复重塑作用及机制，旨在为干细胞治疗骨质疏松性骨损伤提供新思路。

Stem cell transplantation technology has great potential in the field of bone repair. However, stem cell migration imaging, directional differentiation and optimization of bone remodeling are urgent problems to be solved. In our previous study, we have successfully developed a new type of PLGA/Lipid composite porous nanobubble, which could be used as ultrasound contrast agents and the carriers for drug delivery. It is preliminarily confirmed that these nanobubbles could be uptaken by bone marrow mesenchymal stem cells (BMSCs) and maintained good ultrasonic imaging performance. BMP-2 bioactive peptide P24 has the ability to induce stem cells to differentiate into osteoblasts. Our work further confirmed that P24 scaffolds could better promote bone defect repair. Bazedoxifene (BZA) activates the estrogen receptor in the osteogenic nucleus to promote bone remodeling and improve bone quality. In this project, we intend to use PLGA/Lipid nanobubbles to load P24 and bazedoxifene (BZA), evaluate the ultrasound tracing performance of BMSCs, which carry drug-loaded nanobubbles within cells, investigate the controlled release behaviors of drug-loaded nanobubbles for regulation of the BMSCs osteogenis differentiation, explore the remodeling effect and mechanism of BZA/P24-PLGA/Lipid nanobubble modified BMSCs on osteoporosis bone injury. This project will provide new ideas for stem cells treatment of osteoporotic bone injury.