珊瑚羟基磷灰石联合浓缩生长因子修复兔颅骨缺损

Cranial defect repair with coralline hydroxyapatite scaffolds in combination with concentrated growth factors in rabbits

目的骨缺损修复是临床一大难题,异质骨材料与生长因子复合以提高骨缺损修复能力近年来成为研究热点。文中旨在探讨异质骨材料中珊瑚羟基磷灰石(CHA)联合浓缩生长因子(CGF)修复骨缺损的效果。方法选24只新西兰兔,随机数字表法分为CHA/CGF+CHA组、CHA/CGF+自体骨组和CHA+自体骨组,每组8只,在每只兔的两侧颅骨上各制备1个直径10mm圆形缺损。术后6周和12周取材,通过Micro-CT及组织学观察评价骨修复效果。结果 Micro-CT结果显示,CHA/CGF+CHA组:术后6周骨缺损区CHA孔隙中有较多的新骨形成;术后12周CHA孔隙中有大量的新骨形成,骨密度明显增加,CHA部分降解吸收。CHA/CGF+自体骨组:术后6周邻近骨床的CHA孔隙内有少量新生骨长入;术后12周CHA孔隙内的新骨量明显增加。CHA+自体骨组:术后6周自体骨与骨床交界处有骨痂形成,边界模糊;术后12周自体骨与周围骨床完全融合,边界不清。CHA/CGF+CHA组术后6周和12周新骨量多于CHA+自体骨组[(39.00±7.61)mm3vs(32.12±6.55)mm3,(49.75±2.36)mm3vs(39.45±7.02)mm3,P<0.05],骨密度多于CHA+自体骨组[(308.30±29.82)mg/m L vs(256.85±151.25)mg/m L,(389.00±31.87)mg/m L vs(302.53±127.05)mg/m L,P<0.05],在术后12周,CHA/CGF+CHA组新骨量和骨密度与CHA+自体骨组差异无统计学意义(P>0.05)。组织学观察结果:CHA+自体骨组术后6周植入的自体骨与骨床之间有新骨形成,并有少量结缔组织长入;术后12周,自体骨与周围骨床完全融合,边界不清。CHA/CGF+CHA组术后6周骨缺损区CHA孔隙内有散在的新骨形成;术后12周,CHA孔隙内有大量新骨形成并相互融合,部分CHA降解吸收。CHA/CGF+自体骨组术后6周近骨床的CHA孔隙中有少量编织骨长入;术后12周,新生骨质及类骨质面积增大,但缺损中央区域的CHA孔隙内仅有结缔组织充填,无新骨形成,CHA部分降解吸收。结论 CHA与CGF联合使用能有效地促进骨愈合,CHA/CGF复合人工骨是理想的骨移植替代材料。

Objective Bone defect repair remains a challenge in regenerative medicine, which has triggered a research upsurge on improving the bone repairing effect using heterogeneous bone combined with growth factors. The aim of this study was to evalu- ate local bone formation following surgical implantation of coralline hydroxyapatite （CHA） , a heterogeneous bone, in combination with the concentrated growth factor （CGF）. Methods This randomized prospective study included 24 New Zealand rabbits, which were e- qually divided into a CHA/CGF＋CHA, a CHA/CGF＋autograft and a CHA＋autograft group. A defect 10 mm in diameter was made in the parietal bone of each animal and filled with CHA/CGF, CHA or autograft. At 6 andl2 weeks after the operation, we observed the bone formation by micro-CT and histological examination. Results The bone volume （BV） was significantly higher in the CHA/CGF＋CHA than in the CHA＋autograft group both at 6 weeks （ [ 39.00± 7.61] vs [32.12±6.55] mm3, P〈O.05） and at 12 weeks after the operation （[49.75±2.36] vs [39.45±7.02] mm3, P〈O.05）, and so was the bone mineral density （BMD） （[308.30±29.82] vs [256.85±151.25] mg/mL, P〈0.05; [389.00±31.87] vs [302.53±127.05] mg/mL, P〈0.05）. Histological examination showed that the new bone was distributed throughout the CHA scaffold in the CGF/CHA group at 6 weeks, and the new bone was observed only in the periphery region of the CHA scaffold in the CHA group. The bone defects in the CGF/CHA group were fully repaired at 12 weeks, while those in the CHA group were partly repaired with bone and fibrous tissue in the central region of the defects. Conclusion Combination of CHA with CGF could effectively enhance bone heal- ing. CHA/CGF compound artificial bone is an ideal substitute in bone transplantation.