"In vivo tissue-engineered" valved conduit with designed molds and laser processed scaffold.

BACKGROUND: "In body tissue architecture" technology is a practical concept of regenerative medicine that uses the living recipient body's reaction to a foreign object as a reactor for autologous tissue organization. A novel autologous valved conduit was produced by creating a specially designed conduit-mold composite and elastomeric scaffold for this unique in vivo tissue engineering. METHODS: Convex and concave plastic molds assembled with a small aperture of 500-800 microm were inserted into a microporous elastomeric conduit scaffold. The assembly was placed in a subcutaneous pocket of Japanese white rabbits for 1 month. The molds were pulled out from the edge of the harvested implant to obtain the valved conduit. RESULTS: Homogenous and well-balanced trileaflet of membranous tissue was developed in the optimized aperture of molds. The valve leaflet closed and opened rapidly in synchronization with the backward and forward flow of the pulsatile flow circuit in vitro. CONCLUSIONS: A tissue-engineered conduit incorporated with a functional autologous trileaflet valve was developed in an in vivo reactor by optimizing the microstructures of conduit scaffolds and newly designing the composite molds. The method holds promise for a safe, biocompatible, and economical heart valve prosthesis.

Architecture of an in vivo-tissue engineered autologous conduit "Biovalve".

As a practical concept of regenerative medicine, we have focused on in vivo tissue engineering utilizing the foreign body reaction. Plastic substrates for valvular leaflet organization, consisting of two pieces assembled with a small aperture were inserted into a microporous polyurethane conduit scaffold. The assembly was placed in the subcutaneous spaces of Japanese white rabbits for 1 month. After the substrates were pulled out from the harvested implant, valve leaflet-shaped membranous tissue was formed inside the tubular scaffold as designed. The valve leaflet was composed of the same collagen-rich tissue, with the absence of any elastic fiber, as that which had ingrown or covered the scaffold. No abnormal collection or infiltration of inflammatory cells in the leaflet and the scaffold could be demonstrated. According to the immunohistochemical staining, the leaflet was comprised of numerous vimentin- or alpha-SMA-positive cells, corresponding to fibroblasts or myofibroblats, but contained no desmin-positive cells. The analysis of the video data of the valve movement showed that, in synchronization with the backward flow in the diastolic phase, the valve closed rapidly and tightly and, in the transition phase of the flow direction, the valve opened smoothly without flapping or hitting the scaffold wall. Using mold designs, consisting of two different plastic substrates and the tubular scaffold, in conjunction with "in body tissue architecture," the complex 3-dimensional autologous conduit-typed Biovalve was developed for the first time.