Ca-P涂层镁合金支架负载缓释微球修复股骨缺损

Reparation of femoral defects with a Ca-P coated magnesium alloy scaffold carrying sustained release microspheres

背景:以往研究多单独探讨镁合金或含生长因子核壳微球的骨再生促进作用,但有关镁合金支架联合含成纤维细胞生长因子2(fibroblast growth factor-2,FGF-2)和骨形态发生蛋白2(bone morphogenetic protein-2,BMP-2)核壳微球的骨修复效果未见相关报道。目的:观察Ca-P涂层ZK60镁合金支架负载缓释微球修复大鼠股骨缺损的效果。方法:采用同轴静电喷雾技术制备负载FGF-2和BMP-2的聚乳酸-羟基乙酸共聚物和聚左旋乳酸壳-核控释微球,将其填入ZK60镁合金中空管状支架中,在镁合金表面进行Ca-P涂层。将Ca-P涂层ZK60镁合金支架与无涂层ZK60镁合金支架分别浸泡于Hanks液中30d,检测抗腐蚀性能。取18只SD大鼠,建立股骨缺损模型,随机分6组干预,空白组不植入任何材料;ZK组植入Ca-P涂层ZK60镁合金;FGF组植入负载FGF-2微球的Ca-P涂层ZK60镁合金,BMP组植入负载BMP-2微球的Ca-P涂层ZK60镁合金,DUAL组植入负载FGF-2微球与BMP-2微球的Ca-P涂层ZK60镁合金(核内、壳内均含有FGF-2和BMP-2,生长因子同时释放),SEQ组植入负载FGF-2/BMP-2微球的Ca-P涂层ZK60镁合金(FGF-2在壳内,BMP-2在核内,生长因子序贯释放),术后8周进行骨缺损区Micro-CT和骨组织病理切片观察。结果与结论:(1)浸泡在Hanks溶液中30 d后,无涂层ZK60镁合金表面出现了明显大腐蚀坑,Ca-P涂层ZK60镁合金表面仅可见腐蚀裂痕;(2)Micro-CT显示,空白组外表覆盖了一层软组织,缺损区内部几乎为空的;ZK组缺损区域内有组织生成,但未填满缺损区域;FGF组较ZK组新生组织较多,但缺损区域也未完全填充;BMP组和DUAL组缺损区内部填满了新生组织,DUAL组的组织密度较大;SEQ组缺损区填满了组织且组织密度最大;(3)骨组织病理切片显示,空白组骨缺损明显,ZK组缺损部位有所修复,FGF组、BMP组、DUAL组修复较ZK组好,SEQ组修复效果最佳;(4)结果表明,负载FGF-2/BMP-2缓释微球的Ca-P涂层镁合金支架可促进骨再生。

BACKGROUND:Previous studies often discuss that magnesium alloy or core-shell microspheres containing growth factors can promote bone regeneration,but there are no relevant reports on the bone regeneration effect of magnesium alloy scaffolds combined with core-shell microspheres containing fibroblast growth factor-2(FGF-2)and bone morphogenetic protein-2(BMP-2).OBJECTIVE:To investigate the effect of Ca-P coated ZK60 magnesium alloy scaffolds combined with core-shell microspheres in the rats with femoral defects.METHODS:The poly(lactic-co-glycolic acid)and poly-L-lactic acid core-shell sustained release microspheres loaded with FGF-2 and BMP-2 were prepared by means of coaxial electrostatic spraying,and they were filled into the hollow tubular scaffolds of ZK60 magnesium alloy.Ca-P coating was applied to the surface of the magnesium alloy.The Ca-P coated ZK60 magnesium alloy scaffolds and uncoated ZK60 magnesium alloy scaffolds were immersed in Hanks solution for 30 days,and then the corrosion resistance of the alloys was tested.Eighteen Sprague-Dawley rats were randomly divided into six groups,and the model of femoral defects was established in each rat.The defects were implanted with nothing(Blank group),Ca-P coating ZK60 magnesium(ZK group),Ca-P coating ZK60+FGF microspheres(FGF group),Ca-P coating ZK60+BMP microspheres(BMP group),Ca-P coating ZK60+FGF+BMP microspheres(DUAL group,release of the growth factor at the same time),or Ca-P coating ZK60+FGF/BMP microspheres(SEQ group,sequential release).The rats were sacrificed at 8 weeks postoperatively.The defects were evaluated by gross observation,Micro-CT and bone tissue pathological observation.RESULTS AND CONCLUSION:(1)After 30 days of immersion in Hanks solution,there was a significant corrosion pit on the surface of uncoated ZK60 magnesium alloy,while only corrosion cracks were visible on the surface of Ca-P coated ZK60 magnesium alloy.(2)The Micro-CT results showed that the bone defect of the BLANK group was obvious,and was only covered with a layer of soft tissue.The defect site of ZK group was repaired,but not completely.The repair of FGF group was better than that of the ZK group,but the repair was still incomplete.The defects of BMP and DUAL groups were filled with new tissues,and the tissue density was higher in the DUAL group than the BMP group.The repair effect of SEQ group was the best with the highest density of the new tissues.(3)The histopathological sections of bone tissues showed that the bone defect was obvious in the BLANK group,and the defect was somewhat repaired in the ZK group.The defect repair of FGF group,BMP group and DUAL group was better than that of ZK group,and the repair effect of SEQ group was the best.To conclude,Ca-P coated magnesium alloy scaffolds carrying sustained release FGF-2/BMP-2 microspheres can promote bone regeneration.