基于嵌合核酸适配体构建细胞坏死响应性材料实现主动调控血管新生

项目名称： 基于嵌合核酸适配体构建细胞坏死响应性材料实现主动调控血管新生

项目编号： No.51273106

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 杜亚楠

作者单位： 清华大学

项目金额： 85万元

中文摘要： 组织工程重大挑战之一是如何保证移植物（细胞/材料）与体内血管网融合，建立新生血供从而促进组织再生，最终替换坏死组织功能。调控血管新生，使其在需要血供再生的坏死组织中可控实现是亟待解决的前沿问题。本计划首次尝试将坏死细胞/组织分泌的ATP作为响应信号，即时即地转化为促血管新生生长因子（PDGF）的生物信号，实现主动式、指向性地诱导血管新生。通过创新性的ATP-PDGF嵌合适配体设计，实现ATP响应下PDGF从水凝胶材料中的可控释放,模拟体内响应性释放生长因子的促血管再生。同时提出高度系统和整合的方案从分子、材料、细胞和活体各水平上验证此智能材料的功效。其中在细胞水平上结合微加工技术建立新型仿血管多层结构的双环共培养体外模型，实现对细胞坏死反馈的体外血管新生仿生模拟。基于此响应智能材料实现的指向性血管新生预期会促进坏死细胞/组织的修复与再生，并辅助组织工程产品移植后与宿主血管网的融合和

中文关键词： 核酸适配体；生物响应；生物材料；血管新生；组织修复

英文摘要： One of the major challenges of tissue engineering is how to ensure the integrative fusion of the transplanted grafts (cell and biomaterial) with the host vascular network and the establishment of the neo blood supply in order to promote tissue regeneration and ultimately replace the functions of the necrotic tissues. The regulation of on-demand angiogenesis in the necrotic tissue is cutting-edge issues for investigation. This proposal is the first attempt to take necrotic cells / tissues secreted ATP, as a response signal, which are instantly translated into biological signals of angiogenic growth factor (PDGF), thus achieving the active and directional induction of angiogenesis and establishment of the vascular network. Chimeric ATP-PDGF aptamers are innovatively designed to realize the ATP-responsive release of PDGF growth factors from a hydrogel-based biomaterial, which recapitulates responsive release of angiogenic growth factor in vivo. Meanwhile, highly systematic and integrated plans are laid out to verify the effectiveness of this responsive smart material from molecular, material, cellular and in vivo levels respectively. In particular, micro-fabrication technology is adopted to create novel bilayered in vitro model for co-culture to imitate the multilayer structure of the native vasculature, which real

英文关键词： Aptamer；Bio-responsive；Biomaterials；pro-angiogenesis；wound healing