Development of Poly(1,8-octanediol-co-citrate-co-ascorbate) Elastomers with Enhanced Ascorbate Performance for Use as a Graft Coating to Prevent Neointimal Hyperplasia

Abstract

Small-diameter expanded polytetrafluoroethylene (ePTFE) graft surfaces have poor long-term patency due to limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia. Multifunctional elastomers that coat the ePTFE graft surface to promote EC adhesion while simultaneously inhibiting intimal hyperplasia are highly desirable. Poly­(diol-co-citrate) (PDC), a thermoset elastomer, is biodegradable, biocompatible, and mimics vascular mechanical properties. Engineering antioxidant components into PDC polymeric structures improves biocompatibility by attenuating oxidative stress yet is limited by bioavailability. Herein, we develop a new ascorbate protection and deprotection strategy (APDS) for loading bioactive ascorbic acid into the structure of PDC elastomers to improve poly­(1,8-octanediol-co-citrate-co-ascorbate) (POCA) prepolymer ascorbate activity. Elastomers cured from APDS POCA prepolymers provide twice the active ascorbate sites on the elastomer surface (35.19 ± 1.64 ng mg–1 cm–2) versus unprotected POCA (Un.POCA, 18.31 ± 0.97 ng mg–1 cm–2). APDS POCA elastomers displayed suitable mechanical properties for vascular graft coating [Young’s modulus (2.15–2.61 MPa), elongation (189.5–214.6%) and ultimate tensile strength (2.73–3.61 MPa)], and superior surface antioxidant performance through 1,1-diphenyl-2-picrylhydrazyl free radical scavenging and lipid peroxidation inhibition as compared to poly­(1,8-octanediol-co-citrate) (POC) and Un.POCA. Hydrolytic degradation of APDS POCA occurred within 12 weeks under physiological conditions with a mass loss of 25.8 ± 3.4% and the degradation product retaining ascorbate activity. APDS POCA elastomer surfaces supported human aortic endothelial cell proliferation while inhibiting human aortic smooth muscle cell proliferation in vitro. APDS POCA elastomer surfaces displayed superior decomposition of S-nitrosothiols compared to POC and Un.POCA. Taken together, these findings indicate the potential of APDS POCA elastomers to serve as bioactive, therapeutic coatings that enhance the long-term patency of small diameter ePTFE grafts.

Preparation and Characterization of Ionic Conductive Poly(acrylic Acid)-Based Silicone Hydrogels for Smart Drug Delivery System

“…In addition, it is a strong reducing agent and one of the essential components in the human body. It is involved in many activities such as activation of collagen synthesis, and scurvy occurs when L-ascorbic acid is deficient [ 42 , 43 , 44 , 45 ].…”

Current trends in bio‐based elastomer materials

“…Since α-and β-carboxyl groups have different reactivities, the degree of cross-linking, mechanical properties, and degradability of CBEs can be adjusted by changing the molar ratio and the kinetics of reaction between citric acid (CA) and diols. [166][167][168][169][170][171][172][173] For example, when a mixture of CA and diols is heated to 160 • C under nitrogen, diols react with α-carboxyl and β-carboxyl of CA to form 3D networks. 174 Recently, efforts are made to improve the modulus and tensile strength of CBEs.…”

Resorbable elastomers for implantable medical devices: highlights and applications

“…introduces alkene groups that enable subsequent modification or crosslinking. PDCs have been applied to develop transient scaffolds for tissue engineering, 80 either alone or with other comonomers, 83,84 owing to their tissue‐matching tensile properties and tunable degradation rates. Zhao et al .…”

“…introduces alkene groups that enable subsequent modification or crosslinking. PDCs have been applied to develop transient scaffolds for tissue engineering, 80 either alone or with other comonomers, 83,84 owing to their tissue-matching tensile properties and tunable degradation rates. Zhao et al modified a PDC prepolymer with N,N 0 -bis(2-hydroxyethyl)ethylenediamine to develop films with Young's modulus that ranged from 5.91 to 32.64 MPa, and its degradation rate was independent of the extent of modification.…”