HU-308药物缓释涂层对骨质疏松大鼠种植体骨结合及新生骨的影响

The effect of HU-308 coated on titanium implants on osseointegration and new bone in osteoporotic rats

目的:研究HU-308药物缓释涂层对骨质疏松大鼠种植体骨结合及新生骨的影响。方法:60只大鼠随机分成2组:对照组(S)15只,骨质疏松组(M)45只。再将M组大鼠随机平均分为M1、M2、M3组,每组15只。在所有大鼠双侧胫骨骭骺端植入种植钉,S、M1组植入普通钛钉,M2组植入肝素-壳聚糖涂层钛钉,M3组植入HU-308/肝素-壳聚糖涂层钛钉。于种植术后4周、8周、12周各组分别随机处死5只大鼠。所有大鼠处死前第18、19天及处死前第3、4天,每日腹腔内注射钙黄绿素15mg/kg。带种植体的胫骨制作不脱钙骨组织磨片,甲苯胺蓝染色,荧光显微镜及光镜下观测计算骨矿化沉积率(MAR)、荧光周长百分数(%L.Pm)、种植体-骨结合率(OI)。结果:4周和8周时,M3组MAR、%L.Pm均与S组无显著性差异(P>0.05),且均显著大于M1和M2组(P<0.05);12周时,S组MAR、%L.Pm均显著小于M1、M2、M3组(P<0.05),M1、M2、M3组间差异不显著(P>0.05)。4周、8周及12周时,S组OI均显著大于M3组;而M3组OI除12周时与M1、M2组无显著差异外,其他时期均显著大于M1、M2组(P<0.05)。结论:1、骨质疏松能抑制种植体周骨矿化沉积和新骨形成,使骨组织塑形改建时间延长,种植体-骨界面骨结合率下降。2、HU-308药物缓释涂层在种植体植入早中期可加快骨质疏松大鼠种植体周新骨形成和骨矿化沉积,促进种植体骨结合。

Objective： To investigate the effect of HU-308 coated on titanium implants on osseointegration and new bone in osteoporotic rats. Methods： Sixty rats were randomly divided into 2 groups： control group（S, 15 rats）, osteoporosis group （M, 45 rats）. The 45 rats in M were randomly divided into 3 groups： M1, M2, M3. Different titanium screws were implanted into the proximal metaphyses of all rats＇ bilateral tibias. 4, 8 and 12 weeks after implantation, 5 of the rats of each group were randomly sacrificed. The rats were given intraperitoneal injection of calcein 15mg/kg each time on the 19th, 18th, 4th and 3rd day before sacrificed. After sacrificed, the tibias with implants were removed to prepare undecalcified grinding slices and measured the mineral apposition rate（MAR）, percent labeled perimeter（%L.Pm） and osseointegration index（OI）. Results： 4 and 8 weeks after implantation, MAR and %L.Pm in group M3 were similar to those of group S（P〉0.05）, and those in group M3 and S were all significantly higher than group M1 and M2（P〈0.05）. 12 weeks after implantation, MAR and %L.Pm in group S were all significantly lower than those in group M1, M2 and M3（P〈0.05）, and the differences among group M1, M2 and M3 were not significant（P〉0.05）. 4, 8 and 12 weeks after implantation, the OI of S were all significantly higher than M3; the OI of M3 were significantly higher than M1 and M2 in 4 and 8 weeks （P 〈0.05）.Conclusion： 1. Osteoporosis could inhibit bone mineralization and bone formation, prolong the bone rebuilding time, and decrease OI in implant-bone interface. 2. HU-308 coated on titanium implants could promote new bone formation and bone mineralization at the early-middle stage of implantation, improve osseointegration in implant-bone interface.