rhBMP-2论文：骨形态发生蛋白-2缓释载体的研究.docVIP

rhBMP-2论文：骨形态发生蛋白-2缓释载体的研究 【中文摘要】因创伤、肿瘤、炎症、先天畸形等因素引起的大段骨缺损修复是现代医学亟待解决的难题。骨形态发生蛋白-2(BMP-2)凭借其良好的骨诱导性,已被广泛应用于骨组织修复的研究中。因此,构建可降解吸收并具有生物活性的BMP-2缓释支架载体成为骨组织工程的发展趋势。为此,本文开展了以下两部分工作：1.本文以硫酸为交联剂,利用壳聚糖分子与硫酸间可逆的电荷相互作用,采用乳化交联法制备了H2S04-壳聚糖微球,又经NaOH溶液处理制得NaOH-壳聚糖微球,通过不同影响因素的考察优化了微球的制备条件。经SEM. IR, XRD等表征,表明NaOH-壳聚糖微球具有与壳聚糖相似的结构和较低的结晶度。以牛血清白蛋白(BSA)为模型蛋白的吸附研究表明,NaOH-壳聚糖微球具有高吸附蛋白的特点,对BSA的吸附能力比H2SO4-壳聚糖微球及壳聚糖原料都高。在此基础上,将NaOH-壳聚糖微球作为rhBMP-2的缓释载体,构建了rhBMP-2/NaOH-壳聚糖/明胶海绵复合支架,研究了复合支架材料对rhBMP-2的体外释放情况。建立了兔临界骨缺损模型,将负载rhBMP-2的壳聚糖微球/明胶海绵复合支架植入缺损部位,考察动物体内长段骨缺损的修复情况。2.本文选用羧甲基纤维素钠(CMC-Na)、羟丙基甲基纤维素(HPMC)、聚乙烯醇(PVA)三种材料对原有的BMP-2载体—多孔磷酸钙骨水泥CPC进行改性,以克服其脆性大、力学差的缺点。从CPC骨粒和骨条两种形式分别考察了改性效果。然后将载rhBMP-2的改性支架材料植入小鼠体内进行异位实验,对比了异位成骨量,考察了改性材料的生物相容性,从而确定最佳改性材料。在此基础上,建立兔临界骨缺损模型,将载rhBMP-2的CMC-Na/CPC、HPMC/CPC复合支架分别植入缺损部位,考察改性支架在动物体内长段骨缺损的修复情况。 【英文摘要】Reconstruction of segmental bone defects caused by trauma, tumors, congenital malformation or corrective osteotomies remains an urgent problem in the orthopaedic field and bone morphogenetic protein-2 (BMP-2) is known for its potent osteoinductive properties in bone regeneration. So. to construct osteo inductic e bioresorbable carriers of BMP-2 has become the development trend in bone tissue engineering. Therefore, this paper carried out the following two studies.1. In this study, H2SO4-chitosan microspheres were prepared based on the reversible ion interaction between chitosan molecules and sulfuric acid using an emulsion-chemical cross linking method, and then the microspheres were treated by NaOH solution to form NaOH-chitosan microspheres. After studying on the influencing factors, the optimal preparing conditions were confirmed. It was found that the NaOH-chitosan microsphere had similar structure with chitosan and lower crystallinity via SEM, IR, and XRD characterizations. In the adsorption study, the NaOH-chitosan microspheres exhibited higher adsorption capacity to model protein BSA compared to H2SO4-chitosan microspheres and chitosan. Then the composite scaf