A biomimetic, bioengineered polymeric pulmonary valve promotes native tissue remodeling and thrombosis-free function in a chronic ovine model

Background Existing biologic valve prostheses are subject to structural valve degeneration, impacting durability. In younger patients, challenges of micro thrombosis and an inability to accommodate somatic growth necessitate repeat valve reinterventions. Biomimicry of native valve structure and function may promote in situ tissue remodeling while reducing thrombosis and long-term degeneration. We examined this framework in the creation of a bioengineered pulmonic valve. Purpose This study evaluated the long-term in vivo mechanical durability, neotissue compatibility, and freedom from thrombosis of a scaffold-based, biomimetic valve in the pulmonary position. A bioresorbable polymeric valve fabricated by double-component deposition (DCD) electrospinning was implanted in a chronic ovine model. Methods Stentless pulmonic valves were fabricated from bioresorbable polycarbonate urethane urea (PCUU) to mimic native pulmonary valve micro- and macro-structural architecture (N = 5). PCUU DCD valves were implanted in the native pulmonary valve position of 60–70 kg Swifter sheep via left thoracotomy under cardiopulmonary bypass, with a planned endpoint of 6 months. No anticoagulation was administered throughout the study. Echocardiography was performed at implantation and monthly thereafter to assess valve function. At 6 months, animals were euthanized and valves explanted for histology, immunohistochemistry, and mechanical testing to evaluate neotissue–scaffold interactions. Results All five animals underwent successful trileaflet pulmonary valve replacement and recovered. Four animals completed the 6-month follow-up; one animal died from a non–valve-related condition after 3 months (sepsis of gastrointestinal origin). At 6 months, all valves demonstrated mild (1+) or less insufficiency. Pathoanatomically, abnormal leaflet motion was observed in one leaflet in all valves, and two animals showed restricted leaflet mobility due to valve oversizing. No thrombosis was observed at any timepoint. Explanted valves demonstrated neotissue formation throughout the leaflets, most prominently at the commissures and annular regions. Endothelialization (CD31), smooth muscle ingrowth (α-SMA), and mature collagen deposition were evident throughout the constructs. Conclusions Bioengineered DCD stentless valves supported neotissue formation throughout the scaffold at 6 months with stable function and no evidence of thrombosis. Valve function and durability were optimal with accurate sizing. This proof-of-concept chronic animal model confirms the feasibility of scaffold-base in situ native valve remodeling.