Transcatheter Decellularized Tissue-Engineered Heart Valve (dTEHV) Grown on Polyglycolic Acid (PGA) Scaffold Coated with P4HB Shows Improved Functionality over 52 Weeks due to Polyether-Ether-Ketone (PEEK) Insert.

Many congenital heart defects and degenerative valve diseases require replacement of heart valves in children and young adults. Transcatheter xenografts degenerate over time. Tissue engineering might help to overcome this limitation by providing valves with ability for self-repair. A transcatheter decellularized tissue-engineered heart valve (dTEHV) was developed using a polyglycolic acid (PGA) scaffold. A first prototype showed progressive regurgitation after 6 months in-vivo due to a suboptimal design and misguided remodeling process. A new geometry was developed accordingly with computational fluid dynamics (CFD) simulations and implemented by adding a polyether-ether-ketone (PEEK) insert to the bioreactor during cultivation. This lead to more belly-shaped leaflets with higher coaptation areas for this second generation dTEHV. Valve functionality assessed via angiography, intracardiac echocardiography, and MRI proved to be much better when compared the first generation dTEHV, with preserved functionality up to 52 weeks after implantation. Macroscopic findings showed no thrombi or signs of acute inflammation. For the second generation dTEHV, belly-shaped leaflets with soft and agile tissue-formation were seen after explantation. No excessive leaflet shortening occurred in the second generation dTEHV. Histological analysis showed complete engraftment of the dTEHV, with endothelialization of the leaflets and the graft wall. Leaflets consisted of collagenous tissue and some elastic fibers. Adaptive leaflet remodeling was visible in all implanted second generation dTEHV, and most importantly no fusion between leaflet and wall was found. Very few remnants of the PGA scaffold were detected even 52 weeks after implantation, with no influence on functionality. By adding a polyether-ether-ketone (PEEK) insert to the bioreactor construct, a new geometry of PGA-scaffold based dTEHV could be implemented. This resulted in very good valve function of the implanted dTEHV over a period of 52 weeks.