微创机械刺激联合"可视化"载药水凝胶血管新生治疗糖尿病大鼠下肢缺血

项目名称： 微创机械刺激联合"可视化"载药水凝胶血管新生治疗糖尿病大鼠下肢缺血

项目编号： No.31200732

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 吕丰

作者单位： 中国医学科学院

项目金额： 23万元

中文摘要： 对于不适合常规外科手术治疗的下肢缺血疾病患者，特别是糖尿病患者，寻找新的治疗方法是下肢缺血临床治疗急需解决的课题，血管新生治疗法作为严重下肢缺血性疾病治疗的新方法受到广泛的关注。本项目巧妙地综合利用了微创技术、影像技术、缓释系统、双重细胞生长因子协同治疗等方法，创新性地提出了微创机械刺激法和VEGF、bFGF双重"可视化"缓控释微球复合水凝胶载药系统的血管新生治疗方法联合治疗糖尿病下肢缺血疾病。微创机械刺激不仅作为一种刺激血管新生的治疗方法，而且孔道正好可以作为血管新生药物的给药位点，缓控释微球复合水凝胶载药系统可以保持药物的生物活性，改善药物的突释行为，实现双重生长因子的有序、可控释放和协同效应，而"可视化"影像技术可以实时监测缓释系统。通过两种治疗方法的有机结合，可以新生若干微细血管，诱导侧支循环形成，改善下肢缺血症状，期望该复合血管新生治疗技术能有效地应用到糖尿病下肢缺血疾病的治疗.

中文关键词： 血管新生；下肢缺血；细胞生长因子；水凝胶；荧光成像

英文摘要： A substitutive therapy for hindlimb ischemia need to be developed because the surgical operation can not be performed for some hindlimb ischemic patients, especially for diabetes patients. As a novel treatment, therapeutic angiogenesis has been paid more and more attention in the therapy of hindlimb ischemia. In this project, mini-invasive mechanical stimulation combinated with visible hydrogel loaded with VEGF and bFGF for therapeutic angiogenesis in hindlimb ischemic diabetic rats will be applied by mini-invasive technology, imaging skill, controlled delivery system and synergetic use of dual cell growth factors. Mini-invasive mechanical stimulation can not only improve angiogenisis but also afford a channel for administration. Drug delivery system loaded with VEGF and bFGF using microsphere and hydrogel as carrier can maintain the bioactivity of drugs and enhance the release effects of dual growth factors in the way of order, controlled and synergetic delivery. In additional, the delivery system can be monitored by visible fluorescence imaging in vivo. By combinated application of both therapeutic angiogenesis, new-born microvessel can form and collateral circulation of blood flow will be improved, thus further clinical symptom of hindlimb ischemia will be relieved. The new therapeutic angiogenesis method can

英文关键词： Therapeutic angiogenesis；hindlimb ischemia；cell growth factor；hydrogel；fluorescence imaging