State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Biomaterials. 2012 Apr;33(10):2880-91. doi: 10.1016/j.biomaterials.2011.12.047. Epub 2012 Jan 13.
To address the growing demand of small-diameter vascular grafts for cardiovascular disease, it is necessary to develop substitutes with bio-functionalities, such as anticoagulation, rapid endothelialization, and smooth muscle regeneration. In this study, the small-diameter tubular grafts (2.2 mm) were fabricated by electrospinning of biodegradable polymer polycaprolactone (PCL) followed by functional surface coating with an arginine-glycine-aspartic acid (RGD)-containing molecule. The healing characteristics of the grafts were evaluated by implanting them in rabbit carotid arteries for 2 and 4 weeks. Results showed that at both time points, all 10 of the RGD-modified PCL grafts (PCL-RGD) were patent, whereas 4 of the 10 non-modified PCL grafts were occluded due to thrombus formation. Scanning electron microscopy (SEM) data showed abundant platelets adhering on the surface of the midportion of the PCL grafts. In contrast, only few platelets were observed on the PCL-RGD surface, suggesting that RGD modification significantly improved the hemocompatibility of the PCL grafts. Histological analysis demonstrated enhanced cell infiltration and homogeneous distribution within the PCL-RGD grafts in comparison with the PCL grafts. Furthermore, immunofluorescence staining also showed a 3-fold increase of endothelial coverage of the PCL-RGD grafts than that of PCL grafts at those two time points. After 4-week implantation, 65.3 ± 7.6% of the surface area of the PCL-RGD grafts was covered by smooth muscle cell layer, which is almost 23% more than that on the PCL grafts. The present study indicates that RGD-modified PCL grafts exhibit an improved remodeling and integration capability in revascularization.
为满足心血管疾病对小直径血管移植物日益增长的需求，有必要开发具有生物功能的替代品，如抗凝、快速内皮化和平滑肌再生。在这项研究中，通过静电纺丝生物可降解聚合物聚己内酯（PCL）制备小直径管状移植物（2.2mm），然后用含有精氨酸-甘氨酸-天冬氨酸（RGD）的分子对其功能表面进行涂层。通过将移植物植入兔颈动脉 2 周和 4 周来评估移植物的愈合特性。结果表明，在这两个时间点，所有 10 个 RGD 修饰的 PCL 移植物（PCL-RGD）都是通畅的，而 10 个非修饰的 PCL 移植物中有 4 个由于血栓形成而闭塞。扫描电子显微镜（SEM）数据显示，大量血小板附着在 PCL 移植物中段表面。相比之下，仅在 PCL-RGD 表面观察到少量血小板，表明 RGD 修饰显著改善了 PCL 移植物的血液相容性。组织学分析表明，与 PCL 移植物相比，PCL-RGD 移植物内细胞浸润和均匀分布增强。此外，免疫荧光染色还表明，在这两个时间点，PCL-RGD 移植物内皮覆盖面积比 PCL 移植物增加了 3 倍。在植入 4 周后，PCL-RGD 移植物的表面面积有 65.3%±7.6%被平滑肌细胞层覆盖，比 PCL 移植物多 23%。本研究表明，RGD 修饰的 PCL 移植物在血管重建中表现出更好的重塑和整合能力。
