Cardiovascular disease (CVD) is the number one cause of death globally. CVD treatments range from dietary to pharmaceutical to surgical interventions. Vascular grafts are used to replace or bypass a damaged or occluded vessel, and prosthetic grafts are used when autologous vein is not available. However, a major limitation, especially of small-diameter prosthetic grafts, is reduced re-endothelization and increased risk of intimal hyperplasia, leading to graft occlusion (restenosis). Hence, it is highly desirable to develop graft surface coating strategies to improve outcomes following graft implantation. Ascorbic acid has been proposed to act as a therapeutic molecule to improve poor graft patency rates. Despite great progress, the difficulty of immobilizing ascorbate on the lumen of expanded polytetrafluoroethylene (ePTFE) grafts persists. Poly(1,8-octanediol citrate)-co-cysteine (POCC) can be coated onto small-diameter ePTFE grafts and provide thiol groups on the lumen of the graft. Herein, we present a coupling strategy that allows a maleimide-functionalized ascorbate analog to be immobilized on POCC via maleimide-thiol “click” chemistry. We use 2-methoxyethoxymethyl (MEM) to protect the 2,3-di-hydroxy groups on ascorbate and introduce a maleimide group at ascorbate C6. The maleimide-functionalized ascorbate MEM analog (mAA-MEM) was prepared by multistep organic synthesis. The chemical structure of mAA-MEM was verified by 1H NMR, FTIR, and mass spectroscopy, and MEM deprotection conditions have been optimized. Antioxidant analysis indicated that mAA-MEM can be conjugated on the surface of POCC elastomer. Mechanical test results indicated mAA-MEM-POCC or mAA-POCC coatings do not alter the elastic modulus of small-diameter ePTFE grafts. Furthermore, human aortic endothelial cell viability tests suggested that POCC and ascorbate-POCC elastomers exhibit excellent biocompatibility. Taken together, all these findings indicate the strategy of POCC elastomer coupling with ascorbate analog can be used as antioxidant therapeutic coatings that have the potential to enhance long-term patency of small-diameter ePTFE grafts.

Maleimide-thiol coupling of ascorbate analog to poly(1,8-octanediol citrate)-co-cysteine elastomer for vascular engineering application

ACS Spring Meeting 2021

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