超临界二氧化碳法构建淫羊藿苷-聚乳酸/羟基磷灰石仿生型骨修复材料

Preparation of icariin-poly(lactic acid)/hydroxyapatite composite bone-graft substitutes by supercritical carbon dioxide method

背景:前期实验采用超临界二氧化碳法制备了具有良好理化性能和生物相容性的聚乳酸/羟基磷灰石材料,但该材料仅具有骨传导活性,缺乏骨诱导活性。目的:构建具有骨传导和骨诱导活性的淫羊藿苷-聚乳酸/羟基磷灰石仿生型骨修复材料。方法:通过超临界二氧化碳法制备每克材料中含淫羊藿苷10^(-4),10^(-5),10^(-6) mmol的淫羊藿苷-聚乳酸/羟基磷灰石骨修复材料,分别记为IC-PLA/HA(1000)、IC-PLA/HA(100)和IC-PLA/HA(10),以聚乳酸/羟基磷灰石骨修复材料为对照,通过生物力学性能、孔隙率、缓释特性、扫描电镜检测,筛选出淫羊藿苷的最佳复合比例。结果与结论:(1)IC-PLA/HA(1000)组、IC-PLA/HA(100)组和IC-PLA/HA(10)组的压缩强度与弹性模量与对照组比较均无差异;(2)各组材料孔隙率均大于75%,IC-PLA/HA(1000)组、IC-PLA/HA(100)组和IC-PLA/HA(10)组的孔隙率与对照组比较均无差异;(3)IC-PLA/HA(1000)组、IC-PLA/HA(100)组和IC-PLA/HA(10)组材料淫羊藿苷释放在前3 d较快,以后逐渐下降,且下降速率减慢,但7 d后淫羊藿苷释放处于一个缓慢下降的平台期,其中IC-PLA/HA(100)组各时间点淫羊藿苷释放量接近前期实验证实的淫羊藿苷有效浓度10^(-7) mmol/L;(4)扫描电镜显示IC-PLA/HA(100)组材料中,羟基磷灰石与聚乳酸混合均匀,可见微球,淫羊藿苷在材料中不易识别,材料孔径在50-150μm之间;(5)结果表明,构建的淫羊藿苷-聚乳酸/羟基磷灰石仿生型骨修复材料具有良好的力学性能及缓释性能。

BACKGROUND： Our previous findings have shown that poly（lactic acid）/hydroxyapatite （PLA/HA） composite biomaterials prepared by the supercritical carbon dioxide method have good physiochemical properties and biocompatibility. However, the composite materials only have osteoconductivity but no osteoinductivity. OBJECTIVE： To prepare icariin-PLA/HA （IC-PLA/HA） composite biomaterials with good osteoconduction and osteoinduction. METHODS： The supercritical carbon dioxide method was used to prepare IC-PLA/HA composite biomaterials containing 10-4, 10-5, 10-6mmol/g IC, named as IC-PLA/HA（1 000）, IC-PLA/HA（100） and IC-PLA/HA（10）. PLA/HA composite material served as controls. Biomechanical properties, porosity, sustained release characteristics were detected, and scanning electron microscope observation was performed, in order to screen out the optimal IC content in the composite materials. RESULTS AND CONCLUSION： （1） Compressive strength and elastic modulus of IC-PLA/HA（1 000）, IC-PLA/HA（100） and IC-PLA/HA（10） showed no difference from those of PLA/HA. （2） The porosity of all the composite materials was over 75%, and there was still no difference among groups. （3） The IC release from IC-PLA/HA was faster within the first 3 days, and then reduced gradually. However, after 7 days, the IC release plateaued, and the IC release amount from the IC-PLA/HA（100） was close to 10-7mol/L that had been confirmed to be an effective and safe concentration in the previous experiments. （4） Under the scanning electron microscope, HA and PLA were mixed homogeneously and IC was difficult to be identified. The pore size of the IC-PLA/HA（100） ranged from 50 μm to 150 μm. Overall, the IC-PLA/HA composite biomaterials have good mechanical and sustained-release properties.