Interfacial Hydrogel Coatings to Improve the Biocompatibility of Bioprosthetic Valves
Roseen, Madeleine Ava
Grande-Allen, Kathryn J
Doctor of Philosophy
Bioprosthetic valves (BPVs) recapitulate physiological blood flow for patients with late-stage heart valve failure, but the fixed xenograft tissues deteriorate over time. BPVs fail in roughly 15 years, requiring over 300,000 replacement surgeries in the US per year. Technologies that increase the lifespan of these valves would decrease the frequency of replacement surgeries and increase patient quality of life. Failure of BPVs is not well understood but is thought to be due to the altered properties of BPVs compared to native valves and their interactions with the body. BPVs are fixed with glutaraldehyde before implantation, which is necessary to minimize host immune response, but alters the material and mechanical properties of BPVs. To improve their longevity, BPVs need to be shielded from the degrading bodily interactions and their physiological properties restored. Towards this goal, a hydrogel coating method was optimized and applied to BPV tissue. Hydrogels are well-characterized for their biocompatibility and tunable characteristics. Herein we evaluated the use of two hydrogels – poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) diacrylamide – for their ability to bind to the surface and improve the characteristics of BPVs. Initially, the coating method was verified for efficacy on a BPV model system using only PEGDA. The model demonstrated that the coating method was successful in depositing a hydrogel layer which significantly reduced protein adhesion compared to uncoated controls, an important improvement. The coating was then transitioned to glutaraldehyde-fixed tissue to assess its efficacy on BPVs. Both hydrogels showed significant, near-continuous coating along the surface, as well as the restoration of physiologically lower protein adhesion levels and mechanical stiffness. These results confirm that the coating method optimized during this research can alter BPVs and has the promise to transform this important medical device for the better.
bioprosthetic valves, surface coatings, hydrogel coating, heart valves