Unfixed, xenogeneic extracellular matrix for crimp damage-resistant and regenerative transcatheter heart valve prostheses

In this Phase I SBIR application, ViVita Technologies, Inc. (Davis, CA) aims to validate its patented technology (SPEAR PlatformTM; US 9,220,733) towards development of unfixed, immune-compatible, and regenerative xenogeneic biomaterials for transcatheter heart valve replacements. In the U.S., 130,000 heart valve replacement procedures are performed annually, a $2 billion burden. Glutaraldehyde-fixation of bioprosthesis biomaterials only permits longevity of ~10 years in adults due to chronic immune rejection and resultant mechanical failure of the biomaterial. Further, fixed biomaterials are incompatible with recipient cellular repopulation and regenerative turnover; thus, they are non-living solutions. These deficiencies led the National Heart, Lung, and Blood Institute: Cardiac Surgery Working Group to recommend future support of basic biomaterial research for valve bioprostheses to improve durability. By targeting removal of the actual immunological barriers (i.e., cellular and non-cellular antigens), the SPEAR PlatformTM produces unfixed biomaterials (BARETM patches; US 9,827,350) that avoid rapid immune destruction, while maintaining the native extracellular matrix (ECM) structure-function relationships critical for implant longevity and function. BARETM patches (1) elicit minimal graft-specific adaptive immune response, thereby avoiding immune-mediated damage and associated calcification, (2) appear as “self” to the innate immune system, facilitating integration with recipient tissue, and (3) promote rapid non-immune cellular repopulation and resultant regeneration into patient tissue. To broaden the reach of our technology beyond surgical valve replacements to include transcatheter alternatives, thinner BARETM patches generated from porcine pericardium (BARE-Thin) will be necessary. Delivery of transcatheter aortic valve replacements (TAVRs), results in unavoidable crimping of the valve biomaterial. Concerns have been raised that crimp-induced damage of valve biomaterials compromises TAVR durability. Therefore, a biomaterial that avoids crimp damage may enable greater TAVR durability. Further, pro-regenerative biomaterials which can be replaced by the patient’s tissue have the potential to be a lifelong solution. This proposal will determine feasibility of BARE-Thin as a crimp-damage resistant TAVR biomaterial. TAVRs will be manufactured from BARE-Thin or glutaraldehyde fixed-porcine pericardium and crimped; biomaterial properties will be quantified to characterize resistance to damage and resultant effect on in vitro durability (Goal 1). Additionally, conversion rate of BARE-Thin into recipient tissue will be quantified from in vitro resorption (collagenase digestion model) and in vivo turnover (6-month ovine TAVR model) studies (Goal 2). Like our previous SBIR efforts, all Goals have been developed in collaboration with our strategic partner, a leading heart valve manufacturer. Successful completion of this Phase I work will provide critical insight and validation of BARE-Thin as a next-generation TAVR biomaterial, overcoming concerns over crimp related damage and limited longevity of current bioprostheses, by providing a crimp resistant, pro-regenerative biomaterial which affords a lifelong cure. Project Number: 1R43HL180206-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Maelene Wong | Institution: VIVITA TECHNOLOGIES, INC., WOODLAND, CA | Award Amount: $496,255 | Activity Code: R43 | Study Section: Special Emphasis Panel[ZRG1 ISB-Z (13)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R43HL18020601