Hao Dake, Lin Jonathan, Liu Ruiwu, Pivetti Christopher, Yamashiro Kaeli, Schutzman Linda M, Sageshima Junichiro, Kwong Mimmie, Bahatyrevich Nataliya, Farmer Diana L, Humphries Misty D, Lam Kit S, Panitch Alyssa, Wang Aijun
Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA, 95817, United States.
Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA, 95817, United States.
Bioact Mater. 2023 Jun 25;28:467-479. doi: 10.1016/j.bioactmat.2023.06.014. eCollection 2023 Oct.
Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable "living" endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of "off-the-shelf" implantable vascular devices for long-lasting performance in the clinical settings.
可植入血管装置广泛应用于各种血管疾病的临床治疗。然而，目前获批的临床可植入血管装置通常故障率较高，主要原因是其表面缺乏内在的功能性内皮。在此，受血管装置失效的病理机制和天然内皮生理功能的启发，我们开发了新一代基于生物活性聚对二甲苯的保形涂层，以应对血管装置面临的这些挑战。该涂层使用聚乙二醇（PEG）连接子将内皮祖细胞（EPC）特异性结合配体LXW7（cGRGDdvc）引入到血管装置上，以防止血小板粘附并选择性捕获内源性EPC。此外，我们证实了该涂层在人血清中的长期稳定性和功能。使用两种与血管疾病相关的大型动物模型，即猪颈动脉置换模型和猪颈动脉-颈静脉动静脉移植模型，我们证明了该涂层能够在植入后使膨体聚四氟乙烯（ePTFE）移植物的血液接触表面快速生成可再生的“活”内皮。我们期望这种易于应用的保形涂层将为设计“现货供应”的可植入血管装置的表面特性提供一条有前景的途径，使其在临床环境中具有持久性能。
