Novel xenogeneic extracellular matrix biomaterial for cardiovascular prostheses

ABSTRACT In this Phase I SBIR application ViVita Technologies Inc Davis CA aims to validate our patented technology ViVita Process US toward development of an immune compatible xenogeneic leaflet biomaterial for heart valve replacements In the U S heart valve replacement procedures are performed annually a $ million burden Although current bioprostheses glutaraldehyde fixed bovine pericardium Fixed BP or porcine aortic valve are superior to mechanical alternatives the fixation process only permits longevity of years due to chronic immune rejection of the biomaterial and resultant mechanical failure Further this fixation process renders the material incompatible with recipient cellular regeneration and repair These deficiencies have led the National Heart Lung and Blood Institute Cardiac Surgery Working Group to recommend future support of basic biomaterial research for heart valve prostheses To avoid aggressive rejection of implanted untreated animal tissues decellularization protocols focused on removal of immunogenic cellular components however persistence of both cellular and non cellular immunogenic components following decellularization have been demonstrated to elicit in vivo immune responses By targeting removal of the immunological barriers themselves the ViVita Process is capable of producing unfixed biomaterials ViVita BP that avoid the rapid immune destruction experienced by transplanted animal tissues The ViVita Process eliminates the two most critical barriers to discordant xenotransplantation galactose galactose gal and major histocompatibility complex I MHC I and removes of hydrophilic and of lipophilic minor histocompatibility xenoantigens from ViVita BP while maintaining native extracellular matrix ECM structure function relationships In a leporine model ViVita BP elicited minimal graft specific adaptive immune response absence of associated calcification and innate immune recognition as self in origin facilitating integration with recipient tissue In a porcine carotid defect model these benefits resulted in rapid vascular regeneration This proposal will determine the extent to which preservation of native ECM functional properties will allow ViVita BP heart valve leaflets to meet or exceed all in vitro ISO valve hydrodynamic performance assessments Aim Specifically we will compare ViVita BP to current FDA approved materials and identify the correlation between flexural and hemodynamic properties Further this proposal will determine the extent to which native ECM preservation and reduced antigenicity will prevent destructive recipient in vivo graft specific innate and adaptive immune responses to ViVita BP thereby fostering regenerative responses Aim Specifically recipient adaptive innate and regenerative responses to ViVita BP and Fixed BP will be quantified in an ovine intravascular model Both Aims will be performed in collaboration with our strategic partner a leading heart valve manufacturer Successful completion of this Phase proposal will provide critical validation of ViVita BP as a next generation heart valve leaflet biomaterial NARRATIVE American Heart Association estimates the U S prevalence of heart valve disease to be requiring heart valve replacement procedures per year at a cost of $ million Current heart valve replacement biomaterials are subject to recipient immune mediated attack which limits implant longevity and necessitates repeat surgeries to replace damaged valves ViVita Technologies Inc has developed a novel platform methodology ViVita Process to remove immunological barriers from animal derived tissues producing an unfixed bovine pericardium ViVita BP biomaterial which is compatible with patient s immune system integrates with their body and fosters regeneration over time a biomaterial which may prove to be an ideal heart valve replacement biomaterial that can also be translated to diverse cardiovascular applications