Biomatrix/polymer composite material for heart valve tissue engineering.

BACKGROUND Decellularized extracellular matrix has been suggested as a scaffold for heart valve tissue engineering or direct implantation. However, cell removal impairs the physical properties of the valve structure and exposes bare collagen fibers that are highly thrombogenic. Matrix/polymer hybrid valves with improved biological and mechanical characteristics may be advantageous. METHODS Porcine aortic valves were decellularized enzymatically and impregnated with biodegradable poly(hydroxybutyrate) by a stepwise solvent exchange process. Biocompatibility was tested in vitro using cell proliferation and coagulation assays. Proinflammatory activity was assessed in vivo by implantation of matrix/polymer patches in the rabbit aorta. Biomechanic valve properties and fluid dynamics were tested in a pressure/flow-controlled pulse duplicating system. Matrix/polymer hybrid valves were implanted in pulmonary and aortic position in sheep. RESULTS Biocompatibility assays indicated that human blood vessel cells survive and proliferate on matrix/polymer hybrid tissue. In vitro activation of cellular and plasmatic coagulation cascades was lower than with uncoated control tissue. After implantation in the rabbit aorta, matrix/polymer hybrid patches healed well, with complete endothelialization, mild leukocyte infiltration, and less calcification than control tissue. Matrix/polymer hybrid tissue had superior tensile strength and suture retention strength, and hybrid valves showed good fluid dynamic performance. The two valves in aortic position performed well, with complete endothelialization and limited inflammatory cell invasion after 12 weeks. Of the two valves in pulmonary position, one failed. CONCLUSIONS Matrix/polymer hybrid tissue valves have good biological and biomechanic characteristics and may provide superior replacement valves.