Abstract 4573: Advanced In Vitro Protocols for Living, Autologous Tissue-engineered Heart Valves Implanted by Minimally Invasive Procedures
Introduction: Tissue engineering (TE) technologies providing living, autologous heart valves with the capacity of regeneration and growth have shown functionality in chronic animal studies and first human applications. We have previously demonstrated the successful merging of tissue engineering and minimally invasive implantation technologies in a large animal model. Here we investigate the influence of a novel, biomimetic in vitro technology on valve performance.
Methods: Trileaflet heart valves (n=4, 30mm) based on rapidly degrading polymer scaffolds integrated in self-expandable stents were engineered from sequentially seeded ovine vascular derived autologous cells. Valves were grown in-vitro for 19d utilizing combined strain-flow bioreactor systems. Thereafter, valves were crimped (12mm) and delivered minimally invasively (trans-apical) in sheep replacing the native pulmonary valves. Controls were analyzed directly after the crimping/delivery process for structural integrity. Post-operative follow-up (4w) comprised angiography and echocardiography. Neo-tissue analyses included histology, SEM, ECM quantification and biomechanical testing.
Results: TE heart valves showed preserved structural integrity after the crimping and delivery process. The minimally invasive procedure was successful in all implanted valves and adequate functionality was observed up to 4 weeks. Morphological analyses of the leaflets demonstrated a thickened, layered tissue formation comparable to previous animal studies. The TE valve ring structures were integrated into the adjacent native tissue after 4w.
Conclusions: This study demonstrates that based on a novel biomimetic in vitro technology living, tissue engineered heart valves can be generated and implanted by minimally invasive procedures. Process safety and short-term functionality were shown and long-term animal studies are initiated.