可生物降解的玉米蛋白/镁磷骨水泥载体缓释植物雌激素治疗绝经后骨质疏松性骨折的实验研究

Osteoporotic fracture is a serious health issue in the elderly population, especially in postmenopausal women. As a result of bone mass loss, complications, including screws loosing and re-fracture, are significantly higher in osteoporotic fracture patients. Preliminarily, a kind of novel biodegradable magnesium-phosphate bone cement and zein were prepared by our research group. Theoretically, phytoestrogens (soy isoflavones) could be parceled by zein to form drug-loaded microspheres. Were injectable magnesium-phosphate bone cement mixed with the drug-loaded microspheres, composite bone cement with drug sustained release function will be used to the treatment of osteoporotic fractures. The preparation, characterization, biocompatibility and degradability of the drug-loaded bone cement repair system will be systematically studied. The mechanism of drugs sustained release and structure of drug-loaded bone cement system on bone formation will be researched and discussed in vitro and in vivo. Through this study, the relationship between the structure of drug-loaded bone cement and the performance and functionality is expected to be clarified, which would provide a novel idea and method for the development of new bone implant materials with special feature, provided experimental basis for clinical application of injectable drug-loaded bone cement.

骨质疏松性骨折是老年人群，尤其是绝经后妇女的严重健康问题。由于骨量丢失，临床治疗存在早期固定器械松动、后期再次骨折等问题。申请人所在课题组前期已研制出一种新型可生物降解的镁磷骨水泥，具有较好的骨诱导作用，同时还成功合成了天然玉米蛋白载药微球，可用于包裹药物。如能将载药微球与可降解镁磷生物骨水泥复合，制备出具有缓释抗骨质疏松药物功能的骨水泥复合体系，注射植入骨折部位，将同时具备增加强度和改善骨量的作用，对于临床治疗绝经后骨质疏松性骨折具有显著意义。本项目拟在前期工作的基础上，系统地研究载药复合骨修复体系的制备工艺和表征，调整其固化时间和力学性能，并通过体外和体内动物实验来探索并研究这种新型复合载药体系的生物相容性、降解过程、药物缓释调控机制和成骨机制，进而阐明载药骨水泥复合材料的结构-性能-功能三者的关系，为发展新型、有特殊功能的骨植入材料提供新思路和方法，为临床应用提供实验依据。

本研究研制出新型的可注射镁磷骨水泥，该材料具有合适的凝结时间、可注射性和抗压强度。骨水泥浸泡于模拟体液中可逐步降解；采用冷冻干燥法制备载大豆异黄酮的玉米蛋白微球，药物封装率可达80%，在模拟体液中，玉米蛋白逐步降解的同时可缓释负载的大豆异黄酮。此外，本研究制备载药玉米蛋白/镁磷骨水泥复合体系，载药玉米蛋白的加入缩短了镁磷骨水泥的固化时间，提高了抗压强度，改善了可注射性和降解性能。细胞实验表明：载药玉米蛋白/镁磷骨水泥复合体系能促进成骨细胞粘附、增殖和分化。对比单纯骨水泥和直接载药骨水泥，载药玉米蛋白/镁磷骨水泥效果显著提升，同时细胞的ALP、col-I、OPN、OCN和BSP等成骨相关基因表达也明显提高。.将单纯骨水泥、直接载药骨水泥和载药玉米蛋白/镁磷骨水泥复合体系植入到动物体内（兔股骨），研究镁磷骨水泥治疗骨质疏松性骨折的效果、材料在体内释放大豆异黄酮的过程对动物机体的影响及安全性。用上海光源CT 成像系统、HE染色、Masson染色及免疫组化（I型胶原）对骨缺损修复情况进行评价，结果表明：载药玉米蛋白/镁磷骨水泥复合体系在体内能缓释药物，具有优良的生物相容性、降解性和成骨活性，能促进骨缺损修复，有望成为一种新型骨修复材料。