钛种植体表面还原响应型双基因有序控释聚电解质超薄膜的构建

项目名称： 钛种植体表面还原响应型双基因有序控释聚电解质超薄膜的构建

项目编号： No.51201110

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 金属材料学科

项目作者： 彭琳

作者单位： 四川大学

项目金额： 25万元

中文摘要： 多种生长因子在钛种植体-骨界面骨整合过程中的不同阶段发挥不同的生物学效应。利用层层自组装技术可在钛种植体表面交替吸附编码生长因子的可转导DNA以及带相反电荷的聚电解质形成多层基因控释超薄膜，通过改变各组装层间不同基因的分布可使其在植入原位分阶段释放基因，转染周围组织细胞，使生长因子在局部高表达，可弥补应用外源性生长因子的不足。利用还原响应型阳离子聚合物组装DNA可在体内有效保护DNA并促进其在细胞内的逃逸。鉴于骨整合不同阶段对生长因子的需求不同，本课题拟在钛种植体表面构建还原响应型双基因有序控释超薄膜，分别将编码BMP-2和IGF-1的质粒DNA 组装在不同的聚电解质层之间，使其能在骨整合的前期和后期分别释放两种DNA，从而发挥各自的生物学作用。这一原位基因的有序控释方式符合种植体骨整合的生理过程，有望为将来临床应用中提高钛种植体骨整合的效率和缩短骨愈合的时间提供新的研究思路。

中文关键词： 钛种植体；还原响应；层层自组装；基因控释；聚电解质

英文摘要： A variety of growth factors play different biological effects in the process of osseointegration between titanium implant and bone tissue at different stages. Layer by layer assembly technology can be used to prepare gene delivery multilayers by using transduced DNA encoding growth factors and oppositely charged polyelectrolyte on the surface of titanium implants. Changing the distribution of different genes between multilayers allow the implant release different genes at different stages in site. Then the cells of surrounding tissue might be transfected and express growth factors in high concentration in the local which can compensate for the deficiencies of the application of exogenous growth factors. The reduction-sensitive cationic polymer can be used to assemble DNA which will protect the DNA from degradation by the body fluid or blood in vivo as well as effectively promote their escape inside cell. Given the different needs of growth factors in the process of osseointegration at different stages, this study intends to prepare the reduction-sensitive and sequential dual gene delivery polyelectrolyte multilayers on the surface of titanium implants. Plasmid DNA encoding BMP-2 and IGF-1 will be assembled between different polyelectrolyte layers, so that one kind of pDNA can be released in early stage of osseoi

英文关键词： titanium implant；reduction-sensitive；lay-by-lay assembly；gene delivery；polyelectrolyte