Abstract 2469: First In Vivo Experiences with Living, Autologous Tissue-engineered Heart Valves Implanted by Minimally Invasive Replacement Procedures - 8 week follow-up in a large animal model
Introduction: Minimally invasive valve replacement procedures rapidly evolve as alternative treatment option for patients with valvular heart disease. Based on non-living bioprosthetic materials, currently used valve protheses are associated with disadvantages i.e. degenerative dysfunction. Tissue engineering (TE) technologies providing living, autologous heart valves with the capacity of regeneration and growth have shown functionality in long-term animal studies and initial human applications. Here, we introduce a novel strategy combining two promising heart valve technologies: minimally invasive replacement and tissue engineering.
Methods: Trileaflet heart valves (n=8, 30mm) based on rapidly degrading polymer scaffolds and self-expandable stents were engineered from ovine autologous vascular-derived cells. Valves were grown in-vitro for 12d utilizing diastolic loading bioreactor systems. Thereafter, the valves were crimped applying a novel introduction system (12mm). 4 valves were delivered minimally invasively (mini-thoracotomy, trans-apical approach) in sheep replacing the native pulmonary valves. Controls (n=4) were analyzed directly after the crimping/delivery process for viability and structural integrity. Post-operative follow-up comprised angiography and echocardiography. TE valves were explanted after 4 and 8w. Neo-tissue analyses included histology, SEM, ECM quantification and biomechanical testing.
Results: TE heart valves showed preserved structural integrity and viability after the crimping and delivery process. The minimally invasive procedure was successful in all implanted valves and adequate functionality was observed up to 8w. 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 8w.
Conclusions: This in-vivo study demonstrates for the first time the successful merging of the two promising heart valve technologies tissue engineering and minimally invasive replacement procedures. Although representing a preliminary in vivo experience, process safety is shown and extended studies are initiated to assess long-term function.