Development of a heart valve model surface for optimization of surface modifications.

Current bioprosthetic valve replacements (BPVs) are susceptible to myriad complications, including calcification and thrombosis; however, recent research has explored surface modifications to encourage re-endothelialization of the tissue, preventing unwanted blood-tissue interactions. A bioprosthetic valve surface model (BVSM) was developed to facilitate rapid in vitro optimization of surface modification techniques for BPVs. The BVSM was manufactured by photopolymerization of PEGDA and collagen type I and subsequent addition of amine-rich peptide to provide reactive sites for surface modification. This BVSM mimics surface mechanical properties of bioprosthetic valve tissue, as measured by micropipette aspiration. The BVSM successfully mimics the latent toxic effects of glutaraldehyde fixation, as shown through MTT assay results. Amine content, assessed by XPS, was shown to be significantly lower in the BVSM than unfixed tissue. However, incubation of the surface with amine-reactive NHS-PEG-Cy5 revealed even coverage of the BVSM surface, suggesting that there exists sufficient surface reactive groups to anchor surface modifications, and that translation of the modification process to tissue will yield more complete modification of the BPV surface. These results indicate successful construction of a BVSM that mimics essential properties of bioprosthetic valve tissue and its usefulness for rapid in vitro optimization of surface modification methods for endothelialization. STATEMENT OF SIGNIFICANCE: Current bioprosthetic valve replacements are susceptible to many complications, including calcification and thrombosis; however, recent research has explored surface modifications to encourage the integration of the replacement with the native tissue, which would prevent unwanted blood-tissue interactions. However, methods to analyze and optimize such modifications are limited by the complex surface topography, individual variability, and opacity of native tissue. Thus, we have developed a novel bioprosthetic valve tissue model (BVM) which mimics the important features of the bioprosthetic valve tissue and serves as a platform for rapid optimization and testing of surface modification strategies for tissue valves. Thus, the BVM will provide a needed platform to support rapid improvement of clinically available cardiovascular implants.