At present, there are no medical therapies for structural heart valve disease, leaving surgical valve repair or replacement as the only treatment options. Bioprosthetic heart valves (BHV) made from glutaraldehyde-crosslinked tissues, such as bovine pericardium (BP), represent the most widely used heart valve prostheses. While effective short-term at restoring hemodynamic flow, these devices undergo structural valve degeneration (SVD) eventually resulting in their failure. This is accelerated in the pediatric patient population. We hypothesize that an inflammatory response triggered by the accumulation of advanced glycation endproducts (AGE) in BHV is a key mechanism to the failure of heterograft valve prostheses. In this work, we explore the covalent modification of glutaraldehyde-fixed BP with polyethylene glycol (PEG) to protect the tissue from glycation and the accumulation of glycated serum proteins, attenuating the subsequent inflammatory response. Modification of BP was achieved through carbodiimide reaction between amino-terminated PEG and carboxylic groups of BP. PEG coated samples demonstrated reduced albumin infiltration and glycation in vitro relative to unmodified tissues, as evident by fluorescent albumin uptake and immunohistochemistry staining for AGE. The anti-inflammatory effects of PEG coating were evaluated in vitro using activated human monocytes (THP-1). Cells were seeded on the surface of control and PEG-modified BP after exposure to albumin under accelerated glycation conditions, for 24 hours, then washed and placed in resazurin containing media to estimate the amount of viable adherent cells; an 80% reduction in cell count was observed in PEG-modified vs. control BP samples. Analysis of cell media showed a marked increase (215±11%) of TNFα levels in control BP samples relative to nonglycated samples. Samples protected with PEG did not exhibit quantifiable changes in TNFα production (0±8%). The results of these studies provide support of our hypothesis on the role of serum proteins in AGE-mediated SVD. Our findings offer experimental evidence establishing the feasibility and effectiveness of PEG modification as a strategy for improving integrity and durability of implantable cardiovascular devices. Furthermore, this work has the potential to make BHV viable for application in pediatric patients.

Polymer modification of bioprosthetic heart valves to mitigate structural degeneration

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.