TY - JOUR
T1 - One-Pot Covalent Grafting of Gelatin on Poly(Vinyl Alcohol) Hydrogel to Enhance Endothelialization and Hemocompatibility for Synthetic Vascular Graft Applications
AU - Rizwan, Muhammad
AU - Yao, Yuan
AU - Gorbet, Maud B.
AU - Tse, John W.
AU - Anderson, Deirdre E.J.
AU - Hinds, Monica T.
AU - Yim, Evelyn K.F.
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2020/1/21
Y1 - 2020/1/21
N2 - Cardiovascular diseases remain the leading cause of death worldwide. Patency rates of clinically utilized small diameter synthetic vascular grafts, such as Dacron and expanded polytetrafluoroethylene (ePTFE), to treat cardiovascular disease are inadequate because of the lack of endothelialization. Sodium trimetaphosphate (STMP) cross-linked poly(vinyl alcohol) (PVA) could be potentially employed as blood-compatible small diameter vascular graft for the treatment of cardiovascular disease. However, PVA severely lacks cell adhesion properties, and the efforts to endothelialize STMP-PVA have been insufficient to produce a functioning endothelium. To this end, we developed a one-pot method to conjugate cell-adhesive protein via hydroxyl-to-amine coupling using carbonyldiimidazole by targeting residual hydroxyl groups on cross-linked STMP-PVA hydrogel. Primary human umbilical vascular endothelial cells (HUVECs) demonstrated significantly improved cells adhesion, viability, and spreading on modified PVA. Cells formed a confluent endothelial monolayer, and expressed vinculin focal adhesions, cell-cell junction protein zonula occludens 1 (ZO1), and vascular endothelial cadherin (VE-Cadherin). Extensive characterization of the blood-compatibility was performed on modified PVA hydrogel by examining platelet activation, platelet microparticle formation, platelet CD61 and CD62P expression, and thrombin generation, which showed that the modified PVA was blood-compatible. Additionally, grafts were tested under whole, flowing blood without any anticoagulants in a nonhuman primate, arteriovenous shunt model. No differences were seen in platelet or fibrin accumulation between the modified-PVA, unmodified PVA, or clinical, ePTFE controls. This study presents a significant step in the modification of PVA for the development of next generation in situ endothelialized synthetic vascular grafts.
AB - Cardiovascular diseases remain the leading cause of death worldwide. Patency rates of clinically utilized small diameter synthetic vascular grafts, such as Dacron and expanded polytetrafluoroethylene (ePTFE), to treat cardiovascular disease are inadequate because of the lack of endothelialization. Sodium trimetaphosphate (STMP) cross-linked poly(vinyl alcohol) (PVA) could be potentially employed as blood-compatible small diameter vascular graft for the treatment of cardiovascular disease. However, PVA severely lacks cell adhesion properties, and the efforts to endothelialize STMP-PVA have been insufficient to produce a functioning endothelium. To this end, we developed a one-pot method to conjugate cell-adhesive protein via hydroxyl-to-amine coupling using carbonyldiimidazole by targeting residual hydroxyl groups on cross-linked STMP-PVA hydrogel. Primary human umbilical vascular endothelial cells (HUVECs) demonstrated significantly improved cells adhesion, viability, and spreading on modified PVA. Cells formed a confluent endothelial monolayer, and expressed vinculin focal adhesions, cell-cell junction protein zonula occludens 1 (ZO1), and vascular endothelial cadherin (VE-Cadherin). Extensive characterization of the blood-compatibility was performed on modified PVA hydrogel by examining platelet activation, platelet microparticle formation, platelet CD61 and CD62P expression, and thrombin generation, which showed that the modified PVA was blood-compatible. Additionally, grafts were tested under whole, flowing blood without any anticoagulants in a nonhuman primate, arteriovenous shunt model. No differences were seen in platelet or fibrin accumulation between the modified-PVA, unmodified PVA, or clinical, ePTFE controls. This study presents a significant step in the modification of PVA for the development of next generation in situ endothelialized synthetic vascular grafts.
KW - anticoagulation
KW - blood clotting
KW - endothelial adhesion
KW - hemocompatibility
KW - surface modification
KW - thrombogenesis
UR - http://www.scopus.com/inward/record.url?scp=85078659718&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078659718&partnerID=8YFLogxK
U2 - 10.1021/acsabm.9b01026
DO - 10.1021/acsabm.9b01026
M3 - Article
C2 - 32656504
AN - SCOPUS:85078659718
SN - 2576-6422
VL - 3
SP - 693
EP - 703
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 1
ER -