甜菜碱两性离子聚合物和活性多肽构建原位内皮化功能界面的研究

Localized drug delivery from drug-eluting stents (DESs) has been shown to be quite effective and accepted as one of the most promising treatment.methods for preventing restenosis after stenting procedures. However, DES implantation may result in higher risk of late local endothelium regeneration events and late stent thrombotic (LAST) for the clinical long term implantation failure. It is recognized that endothelialization is a promising method for preventing these complications. For this, biofunctional coating modified by zwitterionic polymer and bioactive peptide was designed which the grafting efficiency and surface structure were verified in each step. The effect of the specific ECs adhesion was investigated by the comparison of the human vascular endothelial cells and smooth muscle cells initial attachment onto this coating. The growth, morphology, cell viabilities and endothelial function of the adherent ECs were evaluated. A preliminary in vivo study was also conducted using a rabbit femoral artery injury model to evaluate the in situ re-endothelialization and the anti-restenosis effect. The synergistic effect of zwitterionic polymer and peptide is hopeful to enhance endothelial cells competitive growth and selective migration over smooth muscle cells. The approach described here may provide a basis for preparation of modified surface in cardiovascular implants application to achieve an accelerated in situ endothelialization process.

药物洗脱支架的广泛使用，为高效、微创地治疗心血管疾病提供了良好的手段。然而由药物非选择性抑制效应引起的内皮化延迟和晚期血栓依然是制约其应用的关键问题。本项目针对该关键问题，在前期研究已证实构建内皮细胞选择性功能界面是实现支架内皮原位再生关键的基础上，设计了甜菜碱类两性离子聚合物和活性多肽协同构建的功能界面，以内皮细胞和平滑肌细胞为观察对象，系统研究了材料表面结构、组成对内皮细胞和平滑肌细胞形貌、活性和生长功能的影响；并进一步在动物模型和体内试验中观察支架内皮化和血管内膜增生情况，以期最终获得具有良好生物相容性的内皮细胞选择性功能涂层。为实现支架表面内皮原位再生、有效解决晚期血栓和血管再狭窄问题提供了切实可行的新技术途径。

药物洗脱支架的广泛使用，为高效、微创地治疗心血管疾病提供了良好的手段。然而由药物非选择性抑制效应引起的内皮化延迟和晚期血栓依然是制约其应用的关键问题。本项目针对心血管原位再生材料的关键问题，在前期研究基础上进行更深入更进一步的研究。本研究历时3年，采用不同方法在不同基材表面分别构建基于两性离子聚合物和细胞糖质衣仿生的功能界面，以内皮细胞和平滑肌细胞为观察对象，通过翔实的体内外评价数据证实了内皮细胞相对于其它细胞的选择性粘附，系统研究了材料表面结构、组成对内皮细胞和平滑肌细胞形貌、活性和生长功能的影响为设计新型的心血管植入材料提供了新依据；为实现支架表面内皮原位再生、有效解决晚期血栓和血管再狭窄问题提供了切实可行的新技术途径。. 以上研究共发表有项目标注论文13篇，已获国家授权专利3项。