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

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 be potentially applied in the treatment of diabetes hindlimb ischemia.

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.

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。本项目综合利用了微创技术、影像技术、缓释系统、生长因子治疗等方法，利用微创机械刺激法和结合缓控释水凝胶载药系统进行血管新生治疗下肢缺血性疾病。采用“可视化”卟啉PEG水凝胶为药物载体，缓慢释放生长因子进行血管新生治疗。以卟啉为骨架结构设计的生物材料具有很好的生物安全性和荧光“可视化”性能。利用卟啉分子的功能基团，与PEG的双端基交联形成网络结构，通过分子设计方法设计制备了不同结构的“可视化”卟啉PEG水凝胶。通过优化制备工艺实现了生长因子有效释放, “可视化”水凝胶有效控制生长因子进行血管新生治疗。 “可视化”影像技术实时监测了缓释系统，包括水凝胶材料的定位与降解、药物的释放与跟踪等。通过两种治疗方法的有机结合，新生了若干微细血管，诱导侧支循环形成，改善了下肢缺血症状，该复合血管新生治疗技术能有效地应用到下肢缺血疾病的治疗。