Biomatrix-polymer hybrid material for heart valve tissue engineering

Objectives: Decellularized extracellular matrix (ECM) has been suggested as a scaffold for heart valve tissue engineering as well as for direct implantation. However, cell removal impairs the physical valve properties and bare collagen fibers are highly thrombogenic. We developed hybrid ECM/polymer composite heart valves with improved biologic and physical characteristics.

Material and Methods: Porcine aortic valves were decellularized enzymatically. The ECM scaffolds were impregnated with biodegradable (P(3-co-4HB), 82/18) biopolymer via a stepwise solvent exchange process. Biocompatibility was tested in vitro using by murine & human MTS testing and coagulation assays (platelet factor 4, prothrombin fragments 1&2, complement activation). Pro-inflammatory activity was assessed in vivo by implantation of ECM/polymer patches in the rabbit aorta. Biomechanic properties were tested in a pressure/flow-controlled pulse duplicating system. ECM/polymer hybrid valves were implanted in pulmonary and aortic position (n=4) in sheep.

Results: In vitro assays indicated that human blood vessel cells survive and proliferate on ECM/polymer hybrid tissue, activation of cellular and plasmatic coagulation cascades was as low as seen with native aortic tissue. In vivo, ECM/polymer hybrid patches healed well, with complete endotheliazation, little leukocyte infiltration and less calcification than native control tissue. ECM/polymer hybrid tissue had superior biomechanical properties (tensile strength, suture retention strength) compared to ECM only. Hybrid valves functioned well in vitro, with good fluid dynamics and physiologic leaflet movement. Valves were readily implantable in sheep. There is no evidence of dysfunction while all animals are still under observation.

Conclusions: ECM/polymer hybrid tissue valves have good biologic and biomechanic characteristics and may provide superior replacement valves.