Interfacial Coating Method for Amine-Rich Surfaces using Poly(ethylene glycol) Diacrylate Applied to Bioprosthetic Valve Tissue Models

Abstract

Bioprosthetic heart valve implants are beset by calcification and failure due to the interactions between the body and the transplant. Hydrogels can be used as biological blank slates that may help to shield implants from these interactions; however, traditional light-based hydrogel polymerization is impeded by tissue opacity and topography. Therefore, new methods must be created to bind hydrogel to implant tissues. To address these complications, a two-step surface-coating method for bioprosthetic valves was developed. A previously developed bioprosthetic valve model (VM) was used to investigate and optimize the coating method. Generally, this coating is achieved by first reacting surface amine groups with an NHS-PEG-acrylate while also allowing glucose to absorb into the bulk. Then, glucose oxidase, poly(ethylene glycol) diacrylate (PEGDA), and iron ions are added to the system to initiate free-radical polymerization that bonds the PEGDA hydrogel to the acrylates sites on the surface. Results showed a thin (∼8 μm), continuous coating on VM samples that is capable of repelling protein adhesion (2% surface fouling versus 20% on uncoated samples) and does not significantly affect the surface mechanical properties. Based on this success, the coating method was translated to glutaraldehyde-fixed valve tissue samples. Results showed noncontinuous but evident coating on the surface, which was further improved by adjusting the coating solution. These results demonstrate the feasibility of the proposed two-step surface coating method for modifying the surface of bioprosthetic valve replacements.

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

“…This method produced a robust, substantial coating along the length of the valve specimen. This result was an improvement over our previous report in which a continuous coating was only achievable on a model system and showed patchy and limited deposition on tissue . The minor coating discontinuities found in this study were likely due to sample handling when creating cross sections.…”

“…Assessment of the no PEG-coated control samples verified that this reduction was because of the PEG and not the coating process. These results were anticipated as PEG-based hydrogels have been previously shown to be protein-repellent and are often used to prevent adsorption. , Our previous research analyzing a PEGDA coating on a tissue model system also showed significant protein reduction after the coating was applied …”

“…Our work describes the successful translation of our patented method to coat BPV tissue with poly­(ethylene glycol)-based hydrogels. , Although coating BPVs is a constant effort in this branch of research, a continuous hydrogel coating has not previously been achieved. Herein, we evaluated the use of two different hydrogels: PEGDA and PEGDAA.…”

“…Poly­(ethylene glycol) is distinguished as a Generally Recognized as Safe food-grade polymer, has a broad clinical history, and is commonly used in research because of its surface characteristics. − It is often referred to as a “blank slate” as it is nonadherent but can be modified to suit many different applications. − Hydrogels such as PEGDA have not been examined as potential coatings for BPVs, as previously, the irregular topography and opacity of porcine valve tissues were overwhelming hindrances in performing the photopolymerization processes necessary for hydrogel creation. We recently reported an improved hydrogel coating method that uses a two-step process to initiate hydrogel polymerization via free radicals . This method was shown to be successful on a model system and is not limited by topography or opacity.…”

Fabricating a Low-Cost, Microscopy-Compatible Mechanical Testing Device

“…Tissue engineering studies must show evidence that materials are able to both match the non-pathological mechanical behavior of the diseased or damaged tissue they were designed to replace [2] and withstand the mechanical forces they will be subjected to under physiological conditions [3]. Similar characterization must be performed on any graft [4], stent [5], coating [6], or similar in vivo device [7][8][9] supporting normal physiological processes to ensure proper function and longevity. Mechanical testing is performed on a wide variety of artificial [10], bio-inspired [11], or completely biological [12] materials.…”