Rationale and Methods for a Bio-Engineered Recellularized Heart Valve Based on Decellularized Allograft Tissue Scaffolds

Richard Hopkins of Brown University presented a lecture on October 14, 2003 at 3:00 pm in the Suddath Seminar Room, IBB Building, Georgia Tech Campus.Human allograft transplants offer significant advantages over manufactured mechanical or xenograft tissue valves for many surgical reconstructions. Disadvantages of current generation human valve transplants include: 1.) potential for transmission of disease; 2.) awkward harvesting, processing and storage protocols; 3.) cryopreservation technology which result in various kinds of cellular and tissue damage; 4.) retention of pro-inflammatory and antigenic material (cells and debris) which result in host rejection and scar formation; and 5.) postoperative durability. Tissue engineered aortic valves which are based on processed allogenic valves retain the original design advantages of the semilunar cardiac valve while potentially removing the biological disadvantages. A herd of more than 40 sheep now exists whose hearts contain various variations of tissue engineered semilunar valves. Explant studies will guide further in vitro investigations. Barriers to successful valve tissue engineering include 1.) maintenance of structural and hydraulic performance characteristics; 2.) safety issues with processing that must complete remove offending cells, cell debris and proteins ; 3.) processing, storage and transport issues; 4.) recellularization that requires in vitro pre-treatment or pre-conditioning or post implantation directed auto-recellularization methods for which current knowledge of appropriate signaling proteins, cytokines, etc. is inadequate; and finally, 5.) the engineering criteria for safety, feasibility and efficacy are poorly defined for such bioengineered constructs as they don't fit the mold of manufactured devices or simple biologics. Advances have been made in all of these areas, especially with the development of the large animal valve chronic implant models