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目的 bFGF-2具有促进组织或血管形成的作用,通过局部应用bFGF-2评估其对糖尿病大鼠胫骨种植体周围骨结合的影响。方法采用W/O/W双层乳液法制备负载bFGF-2的聚乳酸-聚羟基乙酸共聚物[poly(lactic-co-glycolic acid,PLGA)]微球。SPF级9周龄雄性SD大鼠35只,体重220～250 g,取10只作为正常对照组,常规饲料喂养;另外25只经高脂高糖饲料喂养后腹腔注射链脲佐菌素(30 mg/kg),其中20只成功建立2型糖尿病模型后,随机分为糖尿病对照组和bFGF-2干预组(n=10)。各组实验动物分别于右侧胫骨近骺端制备种植窝,植入经微弧氧化表面处理的纯钛种植体;其中bFGF-2干预组在种植体植入前从种植窝抽血与bFGF-2 PLGA微球均匀混合,在血液初凝时充分贴附在种植体表面粗糙螺纹间的微孔内。术后4、8周,取出带种植体的胫骨行组织学观察,比较各组大鼠种植体周围骨结合情况。结果术后4周,正常对照组种植体周围大部分被新生薄层的板状骨环绕,骨板连续性较好;而糖尿病对照组种植体周围结合骨板较薄,连续性较差,可见一定量的新生骨,存在较多纤维组织颗粒,同时有广泛的区域骨组织吸收;bFGF-2干预组沿种植体界面可见新骨形成明显,骨板连续性较好。术后8周各组种植体周围骨结合情况与术后4周相似。术后4周,糖尿病对照组种植体周围骨-种植体接触率显著低于正常对照组和bFGF-2干预组,差异有统计学意义(P<0.05);bFGF-2干预组虽然低于正常对照组,但差异无统计学意义(P>0.05)。术后8周,正常对照组及bFGF-2干预组均显著高于糖尿病对照组,差异有统计学意义(P<0.05);bFGF-2干预组与正常对照组比较,差异无统计学意义(P>0.05)。结论将bFGF-2 PLGA微球加载于糖尿病大鼠种植体周围可以形成较好的骨结合效果。
OBJECTIVE bFGF-2 has an effect on promoting tissue or blood vessel formation and its effect on the osseointegration around tibial implant in diabetic rats was evaluated by topical application of bFGF-2. Methods Poly (lactic-co-glycolic acid) (PLGA) microspheres loaded bFGF-2 were prepared by W / O / W double emulsion method. Thirty 35-week-old male Sprague-Dawley rats weighing 220-250 g were randomly divided into normal control group and normal fed group. Another 25 rats were fed intraperitoneally with streptozotocin (30 mg / kg). Twenty of the 20 diabetic models were successfully established and were randomly divided into diabetic control group and bFGF-2 intervention group (n = 10). Each group of experimental animals were prepared in the right tibial metaphyseal implantation nest, implanted by micro-arc oxidation surface treatment of pure titanium implants; bFGF-2 intervention group before implantation of implants from the implant flesh and bFGF- 2 PLGA microspheres were evenly mixed, fully affixed to the surface of the coarse thread in the blood when the initial setting of blood within the pores. At 4 and 8 weeks after operation, the tibia with implants were removed for histological observation. The bone formation around implants in each group was compared. Results Most of the implants in the normal control group were surrounded by the plate-like bone of the nascent lamella after 4 weeks, and the continuity of the plate was good. In the diabetic control group, the bone plate around the implant was thin and the continuity was poor A certain amount of new bone, there are more fibrous tissue particles, while a wide range of regional bone tissue absorption; bFGF-2 intervention group along the implant interface visible new bone formation, bone continuity is good. At 8 weeks after operation, the osseointegration around the implant was similar to that at 4 weeks after operation. At 4 weeks after operation, the bone-implant contact rate in the diabetic control group was significantly lower than that in the normal control group and bFGF-2 intervention group (P <0.05). Although the bFGF-2 intervention group was lower than normal Control group, but the difference was not statistically significant (P> 0.05). At 8 weeks after operation, the levels of bFGF-2 and normal control group were significantly higher than those of diabetic control group (P <0.05); there was no significant difference between bFGF-2 intervention group and normal control group P> 0.05). Conclusion The bFGF-2 PLGA microspheres loaded around the implants of diabetic rats can form a good bone-binding effect.