Poly(ethylene glycol)-Based Coatings for Bioprosthetic Valve Tissues: Toward Restoration of Physiological Behavior

Abstract

Bioprosthetic valves (BPVs) have a limited lifespan in the body necessitating repeated surgeries to replace the failed implant. Early failure of these implants has been linked to various surface properties of the valve. Surface properties of BPVs are significantly different from physiological valves because of the fixation process used when processing the xenograft tissue. To improve the longevity of BPVs, efforts need to be taken to improve the surface properties and shield the implant from the bodily interactions that degrade it. Toward this goal, we evaluated the use of hydrogel coatings to attach to the BPV tissue and impart surface properties that are close to physiological. Hydrogels are well characterized for their biocompatibility and highly tunable surface characteristics. Using a previously published coating method, we deposited hydrogel coatings of poly(ethylene glycol)diacrylate (PEGDA) and poly(ethylene glycol)diacrylamide (PEGDAA) atop BPV samples. Coated samples were evaluated against the physiological tissue and uncoated glutaraldehyde-fixed tissue for deposition of hydrogel, surface adherence, mechanical properties, and fixation properties. Results showed both PEGDA-and PEGDAA-deposited coatings were nearly continuous across the valve leaflet surface. Further, the PEGDA-and PEGDAA-coated samples showed restoration of physiological levels of protein adhesion and mechanical stiffness. Interestingly, the coating process rather than the coating itself altered the material behavior yet did not alter the cross-linking from fixation. These results show that the PEG-based coatings for BPVs can successfully alter surface properties of BPVs and help promote physiological characteristics without interfering with the necessary fixation.

Poly-2-methyl-2-oxazoline–modified bioprosthetic heart valve leaflets have enhanced biocompatibility and resist structural degeneration

“…Several studies have previously evaluated covalently attached PEG for improving the performance and preventing calcification of BHV (31)(32)(33). Although reduced calcification was observed after subdermal implantation in rabbits, the mechanical properties of PEGylated implants were compromised, resulting in an increased elastic modulus and tissue swelling (34).…”

Interpenetrating network design of bioactive hydrogel coatings with enhanced damage resistance

“…Previous studies of PEG hydrogel coatings have demonstrated minimal protein adsorption. 11 Surfaces that are charge-neutral and have a strongly absorbed surface water layer are able to reduce protein adsorption via competitive hydrogen bonding interactions with water molecules. 91 The strong intermolecular hydrogen bonding of pNAGA hydrogels was suspect to increase protein adsorption to the IPN hydrogel coatings.…”

“…[7][8][9] Prior research has demonstrated the acute thromboresistance of these grafts due to the antifouling nature of the hydrogel. 7,8,[10][11][12] Introduction of integrin-targeting proteins promoted endothelial cell adhesion, migration, and a hemostatic phenotype that can support sustained thromboresistance. 7,8,[12][13][14][15][16] Following these promising results, subsequent evaluation in porcine studies revealed surgical damage to the hydrogel coating of the vascular grafts.…”

Recent progress in functional modification and crosslinking of bioprosthetic heart valves

“…Succinimide and acrylate terminated polyethylene glycol (NHS-PEG-Acrylate) was grafted on BHVs and polymerized with polyethylene glycol diacrylate (PEGDA) to obtain PEGylated hybrid BHVs. The PEGylated hybrid BHVs were reported to resist the adsorption of proteins (protein adsorption was reduced by ∼50%) ( Figure 1C and D ) [ 51 , 52 ]. Polyethylene glycol diacrylate (PEGDA) and methacrylated sulphobetaine (SBMA) were hybrid with BHVs through in situ polymerization to resist the deposition of calcium and blood components [ 55 ].…”

“…( D ) PEG-based coatings for bioprosthetic valve tissues. Reproduced with permission from ref [ 52 ]. Copyright 2020 American Chemical Society.…”