CREATING THE IDEAL ARTIFICIAL HEART VALVE

Abstract

BackgroundEmerging evidence from laboratory and clinical investigations suggests that xenogenic tissue heart valves generate an immune response that has been implicated in the eventual failure of these valve constructs. Several attempts have been made to tissue engineer functional heart valve replacements, however, there remain significant barriers to clinical translation. Our novel process for creating a widely available, immunocompatible, shelf-stable xenogenic tissue heart valve aims to address these barriers. The aim of this study was to characterize the in-vitro biomechanical and hemodynamic characteristics of our novel tissue engineered heart valve.Methods and ResultsTwo 23-mm commercially available glutaraldehyde-fixed, stented, xenogenic tissue heart valves were obtained and decellularized with subsequent enzymatic digestion of antigenic epitopes. Human mesenchymal stem cells were used for the recellularization process. Following recellularization, the tissue engineered heart valves were treated for shelf-stability and underwent biomechanical and hemodynamic testing using a pulse duplicator. One 23-mm commercially available glutaraldehyde-fixed, stented, xenogenic tissue heart valve was used as a control for baseline valve performance. All valves tested met the ISO 5840-3:2021 acceptance criteria for cardiovascular implants. Average pulsatile flow effective orifice area was 2.18 cm2 compared to 2.31 cm2 in the control valve. Transvalvular regurgitation fraction was less than 5% during forward flow conditions at 2, 3.5, 5 and 7 L for all valves tested. Visual inspection of the valves confirmed the structural integrity of the leaflets was preserved, with no evidence of tears, prolapse or perforation. Immunofluorescent nuclear staining confirmed the presence of cells on the valve surface before and after hemodynamic testing.Conclusion BackgroundEmerging evidence from laboratory and clinical investigations suggests that xenogenic tissue heart valves generate an immune response that has been implicated in the eventual failure of these valve constructs. Several attempts have been made to tissue engineer functional heart valve replacements, however, there remain significant barriers to clinical translation. Our novel process for creating a widely available, immunocompatible, shelf-stable xenogenic tissue heart valve aims to address these barriers. The aim of this study was to characterize the in-vitro biomechanical and hemodynamic characteristics of our novel tissue engineered heart valve. Emerging evidence from laboratory and clinical investigations suggests that xenogenic tissue heart valves generate an immune response that has been implicated in the eventual failure of these valve constructs. Several attempts have been made to tissue engineer functional heart valve replacements, however, there remain significant barriers to clinical translation. Our novel process for creating a widely available, immunocompatible, shelf-stable xenogenic tissue heart valve aims to address these barriers. The aim of this study was to characterize the in-vitro biomechanical and hemodynamic characteristics of our novel tissue engineered heart valve. Methods and ResultsTwo 23-mm commercially available glutaraldehyde-fixed, stented, xenogenic tissue heart valves were obtained and decellularized with subsequent enzymatic digestion of antigenic epitopes. Human mesenchymal stem cells were used for the recellularization process. Following recellularization, the tissue engineered heart valves were treated for shelf-stability and underwent biomechanical and hemodynamic testing using a pulse duplicator. One 23-mm commercially available glutaraldehyde-fixed, stented, xenogenic tissue heart valve was used as a control for baseline valve performance. All valves tested met the ISO 5840-3:2021 acceptance criteria for cardiovascular implants. Average pulsatile flow effective orifice area was 2.18 cm2 compared to 2.31 cm2 in the control valve. Transvalvular regurgitation fraction was less than 5% during forward flow conditions at 2, 3.5, 5 and 7 L for all valves tested. Visual inspection of the valves confirmed the structural integrity of the leaflets was preserved, with no evidence of tears, prolapse or perforation. Immunofluorescent nuclear staining confirmed the presence of cells on the valve surface before and after hemodynamic testing. Two 23-mm commercially available glutaraldehyde-fixed, stented, xenogenic tissue heart valves were obtained and decellularized with subsequent enzymatic digestion of antigenic epitopes. Human mesenchymal stem cells were used for the recellularization process. Following recellularization, the tissue engineered heart valves were treated for shelf-stability and underwent biomechanical and hemodynamic testing using a pulse duplicator. One 23-mm commercially available glutaraldehyde-fixed, stented, xenogenic tissue heart valve was used as a control for baseline valve performance. All valves tested met the ISO 5840-3:2021 acceptance criteria for cardiovascular implants. Average pulsatile flow effective orifice area was 2.18 cm2 compared to 2.31 cm2 in the control valve. Transvalvular regurgitation fraction was less than 5% during forward flow conditions at 2, 3.5, 5 and 7 L for all valves tested. Visual inspection of the valves confirmed the structural integrity of the leaflets was preserved, with no evidence of tears, prolapse or perforation. Immunofluorescent nuclear staining confirmed the presence of cells on the valve surface before and after hemodynamic testing. Conclusion