干细胞复合I型胶原修饰的PLGA微球治疗骨质疏松性骨缺损

Effect of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with BMSCs on bone de- fects in osteoporotic rats

目的观察骨髓间质干细胞复合I型胶原修饰的聚乳酸聚乙醇酸（PLGA）微球支架注入骨质疏松大鼠股骨转子间骨缺损后骨质量的局部改善情况。方法制备I型胶原修饰的PLGA微球支架，将干细胞与该支架共同培养。40只3月龄雌性SD大鼠去势建立骨质疏松模型，随机分为对照组、缓冲液组、细胞组、微球组、细胞＋微球组，每组8只，于股骨转子间用电钻制作骨缺损，每侧注入不同材料约30μl。术后1个月和3个月每组各处死4只大鼠，取股骨标本用骨密度仪和MicroCTN定转子间骨密度、骨小梁结构。结果骨髓间质于细胞与I型胶原修饰的PLGA微球支架体外培养7d，扫描电镜发现细胞在支架表面黏附、增殖良好。将不同材料分别植入大鼠骨缺损部位，术后1个月，各组转子间骨矿含量及骨密度比较，差异均无统计学意义。细胞＋微球组骨小梁厚度高于缓冲液组和微球组，骨小梁面积百分数高于细胞组和微球组，骨小梁分离度与对照组、缓冲液组和微球组相比有减少趋势，但差异无统计学意义。术后3个月，细胞＋微球组转子间骨矿含量有高于缓冲液组和微球组的趋势，但差异无统计学意义；BMD高于对照组、缓冲液组、细胞组和微球组；骨小梁厚度高于对照组、缓冲液组、微球组和细胞组，骨小梁面积百分数高于对照组和缓冲液组，骨小梁分离度与对照组、缓冲液组、细胞组和微球组相比有减少趋势，但差异无统计学意义。结论骨质疏松部位植入干细胞复合I型胶原修饰的PLGA微球1个月，即可修复骨质疏松部位骨缺损；3个月，可改建骨质疏松部位骨小梁结构，提高骨质量。

Objective To evaluate the bone repair capacity of polylactic acid-polyglycofic acid copolymer （PLGA）/colla- gen type I （CoI） microspheres combined with BMSCs after being injected in intertrochanteric bone defect of osteoporotic female rats. Methods Prepared PLC, A microspheres. The microspheres were coated with CoI. BMSCs of the third passage were cultured with PLGA/CoI microspheres. Forty 3-month-old female SD rats were ovariectomized to establish osteoporotic animal models. The osteoporotic rats were randomly divided into 5 groups, including SHAM group, PBS group, Cell group, MS group and Cell＋MS group. There were 8 rats in each group. Different material was injected into the intertrochanterie bone defect site which was made with electric drill. Four rats of each group were sacrificed at 1 month and 3 months post-operation. The femora were taken to mea- sure the intertrochanteric bone mineral density （BMD） with DEXA and evaluate trabecular stucture with Micro CT. Results Af- ter 7 days of coculture, BMSCs seeded on PLGA/Co[ mierospheres had nice adheranee and proliferation. There was no difference of BMC and BMD among all groups at 1 month post-operation. Tb.Th of Cell＋MS group was higher than that of PBS group and MS group at 1 month post-operation. %Tb.Ar of Cell＋MS group was higher than that of Cell group and MS group at 1 month post-opera- tion. Tb.Sp of Cell＋MS group had a tendence to decrease compared with other groups but there was no statistical difference at 1 month post-operation. After 3 months of operation, the BMC of Cell＋MS group had a tendence to increase compared with that of PBS group and MS group but showed no statistical difference. BMD and Tb.Th of Cell＋MS group was higher than those of other groups. %Tb.Ar of Cell＋MS group was higher than that of SHAM group and PBS group. Tb.Sp of Cell＋MS group had a tendence to reduce compared with other groups but showed no statistical difference. Conclusion The bone defect of osteoporotic site can be repaired 1 month after the injection of the PLGA/CoI microspheres combined with BMSCs. The trabecular reconstruction and bone quality of osteoporotic site can be improved 3 months after the injection.