新型"自膨胀、可降解、抗骨质疏松" 多功能化骨水泥（n-ALD-PAA）用于治疗OVCF的基础研究

The minimal invasive percutaneous vertebroplasty (PVP) or kyphoplasty (PKP) is the state-of-the-art treatment on osteoporotic vertebral compression fractures. The key technique of PVP or PKP is injecting bone cement into the collapsed vertebral bodies in aim to restore vertebral height and strength. However, most of these kinds of single-functional bone cement have no anti-osteoporosis effect resulting high re-fracture rate. In addition, because of no self-expandable characteristic, large amount of bone cement needs be injected. This leads to cement leakages and serious complications. At present, no ideal multi-functional bone cement has been developed. The applicants previously found that a novel kind of anti-osteoporotic, biodegradable and self-expandable cement (n-ALD-PAA ) could be developed by combining alendronate nanoparticle (n-ALD) and polyacrylic acid (PAA) particle with calcium phosphate cement. However, the micro-mechanism of expansion, drug releasing pattern, as well as the effects on bone metabolism are still unknown. Based on previous research findings, our current research work is intended to further investigate the rule of drug releasing of n-ALD and the mirco-mechanism of self-expandable PAA. The effects and mechanism of new materials on osteoblast cell, osteoclast cell and related gene expression such as OPG and RANKL were elucidated by both cytological and molecular experiments. And the effects on osteoporosis vertebral fracture were further investigated. Then, by the OP animal model will be used to clarify the effects of n-ALD-PAA on strengthening and treatment of vertebral body. The applicants believe this project could provide a theoretical and experimental basis for developing a new type of self-expanding bone cement for vertebroplasty.

微创椎体成型术是治疗骨质疏松（OP）椎体压缩骨折(OVCF)的最主要方法，其关键技术是将骨水泥注射至骨折椎体内恢复其高度和强度。而现有骨水泥仅有"单一化功能"：无治疗OP作用，再次骨折发生率高；无自膨胀特性，注射剂量大容易渗漏,导致严重并发症。目前尚无理想的骨水泥材料。我们前期研究发现：联合应用"阿仑膦酸钠纳米微球（n-ALD）"和"吸水树脂（PAA）"改进"生物玻璃基磷酸钙"骨水泥，能够构建新型"自膨胀、可降解、抗OP"的多功能骨水泥（n-ALD-PAA）。但是，该材料微观膨胀机制、药物释放周期规律及对OP骨代谢过程影响的机制尚不清楚。本研究拟在上述基础上，进一步阐明材料的释药规律和膨胀机制；通过细胞学和分子生物学方法分析材料对成骨、破骨细胞功能及OPG、RANKL相关基因的影响，揭示其对OP骨代谢过程的影响机制；通过OP动物模型明确其对椎体的强化及治疗作用，为其临床应用提供理论依据。

微创椎体成型术是治疗骨质疏松（OP）椎体压缩骨折(OVCF)的最主要方法，其关键技术是将骨水泥注射至骨折椎体内恢复其高度和强度。目前临床广泛应用的椎体成形材料是聚甲基丙烯酸甲酯骨水泥。该材料有固化速度快，力学强度高等优点，但也存在着明显的不足：无治疗OP作用，再次骨折发生率高；无自膨胀特性，注射剂量大容易渗漏,导致严重并发症。目前临床尚无可达到理想效果的骨水泥材料。本课题组针对这种情况，制备出可吸水、自膨胀的新型骨水泥（PMMA-PAA二聚骨水泥和PMMA-PAA-Pst三聚骨水泥），并测量其理化性质，力学性能以及其生物相容性。.1.理化性质方面：PMMA-PAA二聚骨水泥和PMMA-PAA-Pst三聚骨水泥混合吸水凝固后可分别膨胀10%与90%，较好的避免了由于骨水泥的体积收缩产生的残余应力导致水泥-假体界面及水泥-骨界面裂隙的产生；且二聚骨水泥及三聚骨水泥相较PMMA骨水泥凝固温度相对降低，面团时间相对更长，较好的避免了骨水泥凝固产热对周围组织的热损伤，并相应增加了骨水泥手术的操作时间，该材料的固化时间及可注射性符合外科手术要求；.2.力学性能方面：PMMA-PAA二聚骨水泥和PMMA-PAA-Pst三聚骨水泥抗压强度及弹性模量相对降低，避免了原聚甲基丙烯酸甲酯骨水泥弹性模量过高导致的临近椎体再骨折；.3.细胞毒性方面;PMMA-PAA二聚骨水泥和PMMA-PAA-Pst三聚骨水泥体外生物活性较PMMA骨水泥有了明显的改善。有利于成骨细胞的粘附、增殖和分化；具有优秀的生物相容性，更好的生物活性，更有利于骨缺损的修复。.上述材料均能够对骨质疏松椎体骨折进行有效力学支撑，同时能发挥一定的成骨活 性，有希望成为新的椎体成型强化材料。