Abstract:
Vascular regeneration and patency maintenance, without anticoagulant administration, represent key developmental trends to enhance small-diameter vascular grafts (SDVG) performance. In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties. However, mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs. Previously fabricated poly(ε-caprolactone) skeleton-reinforced biotubes (PBs) circumvented mechanical issues and achieved vascular regeneration, but orally administered anticoagulants were required. Here, highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens. The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (DMPE)-PEG-conjugated anti-coagulant bivalirudin (DPB) and DMPE-PEG-conjugated endothelial progenitor cell (EPC)-binding TPS-peptide (DPT) modifications possessed functionality conducive to promoting vascular graft patency. Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability. DPB repellent of non-specific proteins, DPB inhibition of thrombus formation, and DPB protection against functional masking of DPT\'s EPC-capture by blood components, which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration. This strategy offers a safe, facile, and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.
摘要:
血管再生和通畅维持,没有抗凝剂给药,代表了提高小直径血管移植物(SDVG)性能的关键发展趋势。体内工程化的自体生物管已成为具有促再生特性的SDVG候选物。然而,机械故障与血栓形成阻碍了生物管作为SDVG的平移前景。先前制造的聚(ε-己内酯)骨架增强的生物管(PBs)规避了机械问题并实现了血管再生,但需要口服抗凝剂.这里,高效和生物相容性的功能修饰被引入到PB腔的活细胞中。1,2-二肉豆蔻酰基-sn-甘油-3-磷酸乙醇胺-N-甲氧基(DMPE)-PEG缀合的抗凝血比伐卢定(DPB)和DMPE-PEG缀合的内皮祖细胞(EPC)结合的TPS-肽(DPT)具有有助于促进血管移植物通畅的功能。DPB和DPT的共修饰迅速达到管腔饱和而不影响细胞活力。非特异性蛋白质的DPB驱避剂,DPB抑制血栓形成,和DPB保护免受血液成分对DPT的EPC捕获的功能性掩蔽,在没有抗凝剂给药的情况下,促进大鼠和犬动脉植入模型的通畅和快速内皮化。这个策略提供了一个安全的,轻而易举,和快速的技术方法,以将额外的功能化传递给组织工程构建体内的活细胞。