胰岛素/聚乳酸-羟基乙酸共聚物微球-纤维蛋白胶的局部应用在1型糖尿病大鼠胫骨种植体骨结合中的作用研究

Effect of local application of fibrin gel loaded with insulin/PLGA microspheres on osseointegration of implants in type 1 diabetic rat tibia

目的考察胰岛素/聚乳酸-羟基乙酸共聚物(PLGA)微球-纤维蛋白胶的局部应用对链脲菌素(STZ)诱导的1型糖尿病大鼠胫骨种植体骨结合及其周围新骨形成的影响。方法将96只SPF级Wistar大鼠随机分为8组:健康大鼠对照组、糖尿病大鼠对照组和6组糖尿病大鼠的种植窝分别注入负载或不负载胰岛素的不同载体材料。每只大鼠的左胫骨植入1个钛种植体。术后第4、8周活杀大鼠,取左胫骨钛种植体骨块复合体作骨磨片,采用数字化图像分析系统测量种植体骨结合率(BIC)及其周围骨小梁面积百分数(BV/TV)。结果术后第4和8周,与健康大鼠对照组相比,糖尿病大鼠对照组的BIC及其BV/TV明显降低;局部应用胰岛素/PLGA微球-纤维蛋白胶组糖尿病大鼠种植体的BIC及其BV/TV明显增加,BIC于第8周、BV/TV于第4、8周与健康大鼠对照组相比均无明显差异。结论通过局部应用胰岛素/PLGA微球-纤维蛋白胶向种植体周围持续递送胰岛素,可促进1型糖尿病大鼠胫骨种植体周围的新骨生成,改善种植体骨结合。

Objective To evaluate the effect of local application of fibrin gel loaded with insulin/poly(lactic-co-glycolic acid)(PLGA)microspheres on the osseointegration of implants and peri-implant new bone formation in the streptozocin(STZ)-induced type 1 diabetic rat tibia. Methods Ninety-six SPF Wistar rats were randomly divided into eight groups:the healthy control group,diabetic control group(no treatment),and six groups of diabetic rats treated locally using carriers containing insulin or not. Each of the rats received one titanium implant in the left tibia. Four or eight weeks after surgery,the rats were sacrificed. Tibial specimens containing the implants were harvested and undecalcified sections of bone samples were obtained. Bone-implant contact(BIC)andbonevolume/totalvolume(BV/TV)weremeasuredusinga digital imageanalysissystem. Results Inthe diabetic control group,the BIC and BV/TV were significantly decreased compared to the healthy control group both at 4 th and 8 th weeks. In the diabetic rats locally treated with fibrin gel loaded with insulin/PLGA microspheres,the BIC and BV/TV were markedly raised,and no significant difference was found in BIC at 8 th week post implantation or in BV/TV at both 4 th and 8 th weeks between the diabetic rats treated with fibrin gel loaded with insulin/PLGA microspheres and the healthy control group. Conclusion Local insulin delivery via fibrin gel loaded with insulin/PLGA microspheres promotes the peri-implant osteogenesis in the STZ-induced type 1 diabetic rat tibia and ameliorates the osseointegration of implants.