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具有 PEG 和细胞黏附肽的生物功能化静电纺丝 PCL-PIBMD/SF 血管移植物用于内皮化。

Biofunctionalized Electrospun PCL-PIBMD/SF Vascular Grafts with PEG and Cell-Adhesive Peptides for Endothelialization.

机构信息

School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Tianjin, 300350, China.

Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin, 300350, China.

出版信息

Macromol Biosci. 2019 Feb;19(2):e1800386. doi: 10.1002/mabi.201800386. Epub 2018 Nov 28.

DOI:10.1002/mabi.201800386
PMID:30485667
Abstract

Artificial small-caliber vascular grafts are still limited in clinical application because of thrombosis, restenosis, and occlusion. Herein, a small-caliber vascular graft (diameter 2 mm) is fabricated from poly(ε-caprolactone)-b-poly(isobutyl-morpholine-2,5-dione) (PCL-PIBMD) and silk fibroin (SF) by electrospinning technology and then biofunctionalized with low-fouling poly(ethylene glycol) (PEG) and two cell-adhesive peptide sequences (CREDVW and CAGW) with the purpose of enhancing antithrombogenic activity and endothelialization. The successful grafting of PEG and peptide sequences is confirmed by X-ray photoelectron spectroscopy. The suitable surface wettability of the modified vascular graft is testified by water contact angle analysis. The surface hemocompatibility is verified by platelet adhesion assays and protein adsorption assays, and the results demonstrate that both platelet adhesion and protein adsorption on the biofunctionalized surface are significantly reduced. In vitro studies demonstrate that the biofunctionalized surface with suitable hydrophilicity and cell-adhesive peptides can selectively promote the adhesion, spreading, and proliferation of human umbilical vein endothelial cells. More importantly, compared with control groups, this biofunctionalized small-caliber vascular graft shows high long-term patency and endothelialization after 10 weeks of implantation. The biofunctionalization with PEG and two cell-adhesive peptide sequences is an effective method to improve the endothelialization and long-term performance of synthetic vascular grafts.

摘要

人工小口径血管移植物由于血栓形成、再狭窄和闭塞,在临床应用中仍然受到限制。本文采用静电纺丝技术,以聚己内酯-聚(异丁基-吗啉-2,5-二酮)(PCL-PIBMD)和丝素蛋白(SF)为原料,制备了一种小口径血管移植物(直径 2mm),然后通过接枝低抗污性聚乙二醇(PEG)和两种细胞黏附肽序列(CREDVW 和 CAGW)进行生物功能化,以增强抗血栓活性和内皮化。X 射线光电子能谱证实了 PEG 和肽序列的成功接枝。通过水接触角分析证实了改性血管移植物具有合适的表面润湿性。通过血小板黏附试验和蛋白质吸附试验验证了表面血液相容性,结果表明,生物功能化表面的血小板黏附和蛋白质吸附显著减少。体外研究表明,具有合适亲水性和细胞黏附肽的生物功能化表面可以选择性地促进人脐静脉内皮细胞的黏附、铺展和增殖。更重要的是,与对照组相比,这种生物功能化的小口径血管移植物在植入 10 周后具有较高的长期通畅率和内皮化。PEG 和两种细胞黏附肽序列的生物功能化是提高合成血管移植物内皮化和长期性能的有效方法。

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