目的研制一种生物可降解载药复合支架，探讨其骨缺损修复和局部长效药物缓释性能。方法采用新型聚（己内酯）-b-聚（丙交酯-co-乙交酯）[poly（caprolactone）⁃b⁃poly（lactide⁃co⁃glycolide），b⁃PLGC]与β-磷酸三钙（β⁃tricalci⁃um phosphate，β⁃TCP）为复合材料基材，通过粒子沥滤、冷冻干燥相分离相结合的技术制备三维多孔b⁃PLGC/β⁃TCP支架并在支架上负载利福平（rifampicin，RFP），通过扫描电镜、热重分析仪、紫外-可见分光光度计、万能拉力试验机等方法对RFP/b⁃PLGC/β⁃TCP支架的微观形态、β⁃TCP的分布、载药量、压缩强度及孔隙率进行表征。制作兔骨缺损模型，分别于骨缺损处植入β⁃TCP/b⁃PLGC支架、RFP/β⁃TCP/b⁃PLGC支架，并设置空白对照组（不植入任何材料），用以评价骨修复效果。结果 b⁃PLGC/β⁃TCP支架的孔隙由直径200~300μm的大孔和直径10~50μm的微孔组成，孔隙分布均匀，贯穿性良好；b⁃PLGC/β⁃TCP支架上、中、下三部分的β⁃TCP的含量分别为49%、52%和52.7%，分布较为均匀，同时β⁃TCP的加入避免了b⁃PLGC支架成型后体积收缩的情况，使支架的孔隙率由20.6%提高到83.4%；b⁃PLGC/β⁃TCP支架的压缩强度为240 kPa，压缩模量为1.0 MPa。RFP/b⁃PLGC/β⁃TCP支架的载药量为3.2%，药物释放初期存在一定的爆发释放，但在爆发释放1周后释放速度减慢，时间可以持续64 d，有助于骨结核病的药物治疗。β⁃TCP/b⁃PLGC支架组、RFP/β⁃TCP/b⁃PLGC支架组骨缺损得到修复，对照组骨缺损未修复。结论 RFP/β⁃TCP/b⁃PLGC支架具有良好的孔隙结构和一定的压缩强度，有望成为骨结核手术中病灶清除后的骨修复与抗结核治疗提供新的方法与材料。%Objective To explore a biodegradable drug⁃loaded composite scaffold and determine its bone regeneration and local long⁃term drug release ability. Methods In this study, RFP⁃loaded a novel poly (caprolactone)⁃b⁃poly (lactide⁃co⁃gly⁃colide)/β⁃TCP composite scaffold was produced using particle⁃leaching/freeze⁃drying technique. And the obtained composite scaffold was characterized by SEM, TGA, UV spectrophotometer, universal testing machine and so on. New Zealand rabbits were used to prepare bone defects, which was treated by the implantation of active artificial bone loaded with or without RFP. The blank group was untreated. Then the repairing effects of the materials were examined. Results The obtained porous scaf⁃fold has inter⁃connected and uniformly distributed pores, and the diameters of pores range from 200 μm to 300 μm. Many mi⁃cropores (10 μm to 50 μm) can be observed on the wall of macropores. The total porosity of the porous composite scaffold can reach as high as 83.4%; the β⁃TCP content of the scaffolds is 51.2%. Meanwhile, the addition of β⁃TCP avoided volume shrinkage compared with b⁃PLGC scaffold; Additionally, the porous composite scaffold has good compressive strength ( 240 kPa) and compressive modulus (1.0 MPa); And the drug loading of the scaffold was 3.2%,which could smoothly release drug for 63 days after a period of burst release for a week. All defects in the experimental groups were radiographically repaired. There were significant differences between the experimental groups and the control group. Conclusion RFP⁃loaded poly (cap⁃rolactone)⁃b⁃poly (lactide⁃co⁃glycolide)/β⁃TCP composite scaffold is expected to benefit in drug therapy and bone repair in the treatment of bone tuberculosis.
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