丝素蛋白纳米羟基磷灰石复合材料的生物安全性  

Biological safety of silk fibroin/nano-hydroxyapatite composites

作　　者：范纯泉[1] 叶晓健[2] 

机构地区：[1]解放军第175医院/厦门大学附属东南医院,全军骨科中心,福建省漳州市363000 [2]解放军第二军医大学长征医院骨科,上海市200001

出　　处：《中国组织工程研究》2016年第38期5650-5656,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(81472071);军队医学科技青年培育计划(15QNP022);南京军区医学科技创新课题面上项目(15MS109)~~

摘　　要：背景:丝素蛋白具有良好的生物相容性、生物降解性、优越的力学性能,与纳米羟基磷灰石的复合可以模拟天然骨组织中的有机无机成分,可以弥补单纯纳米羟基磷灰石力学性能的不足。目的:评价丝素蛋白/纳米羟基磷灰石复合材料的生物安全性。方法:以氯化钙和磷酸氢二铵为原料,丝素蛋白作为调控纳米羟基磷灰石晶体生长的模板,通过共沉淀法合成了丝素蛋白/纳米羟基磷灰石类骨质复合材料。按照国际标准化组织(ISO10993)和国内(GB/T16886)对于生物材料相容性的检测方法和要求,通过体外细胞毒性、全身急性毒性实验、溶血实验来评价丝素蛋白/纳米羟基磷灰石复合材料的生物安全性。结果与结论:(1)丝素蛋白/纳米羟基磷灰石复合材料浸提液与L929细胞共培养后对细胞的形态、代谢及增殖无影响;(2)丝素蛋白/纳米羟基磷灰石复合材料浸提液腹腔注射到小白鼠体内,对小白鼠无明显不良反应;(3)丝素蛋白/纳米羟基磷灰石复合材料浸提液导致的静脉血溶血率为2.39%,小于5%的国际标准;(4)结果提示,丝素蛋白/纳米羟基磷灰石复合材料无细胞毒性,无全身急性毒性反应,不引起溶血反应,具有良好的生物安全性。BACKGROUND： Silk fibroin has excellent biocompatibility, biodegradability and unique mechanical properties. Its composite, silk fibroin/nano-hydroxyapatite, can simulate the composition and structure ofnature bone tissue, contributing to remedying the insufficient mechanical properties of nano-hydroxyapatites. OBJECTIVE： To observe the biological safety of silk fibroin/nano-hydroxyapatite composites. METHODS： Silk fibroin/nano-hydroxyapetite composite biomaterial was synthesized by the coprecipitation method using silk fibroin, calcium chloride and diammonium phosphate as raw materials. According to the demands of International Standard Organization（ISO10993） and Technical Evaluation Standards of Biomedical Materials and Medical Instruments promulgated by Chinese Board of Health（GB/T 16886）, experiments of cell toxicity in vitro, acute toxicity and hemolysis were investigated to evaluate the biocompatibility of silk fibroin/nano-hydroxyapetite composite. RESULTS AND CONCLUSION： L929 cells co-cultured with silk fibroin/nano-hydroxyapatite composite leaching liquor had good cell morphology, metabolism and proliferation. The leaching extract of silk fibroin/nano-hydroxyapatite composite injected into mice intraperitoneally had no significant adverse reactions. And silk fibroin/nano-hydroxyapatite composite extracts caused 2.39% blood hemolysis, less than the international standards 5%. These experimental results on cell toxicity test in vitro, acute toxicity and hemolysis met the demands of ISO10993 and GB/T, which show the biological safety of the silk fibroin/nano-hydroxyapatite composite for clinical application.

关 键 词：丝素蛋白 纳米复合物 羟基磷灰石类 组织工程 生物材料 骨生物材料 纳米羟基磷灰石 生物安全性 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]