Storage And Rehabilitation Of Living Allogenic Heart Valves
Elizabeth Cordoves1, Keith Yeager1, Francois Chesnais, Ph.D.1, V. Reed LaSala, M.D.2, Sharon Fleischer, Ph.D.1, Emmanuel Zorn, Ph.D.1, Giovanni Ferrari, Ph.D.1, Emile Bacha, M.D.2, Gordana Vunjak-Novakovic, Ph.D.1, David Kalfa, M.D., Ph.D.2.
1Columbia University, New York, NY, USA, 2Columbia University Medical Center, New York, NY, USA.
Objectives: There is an urgent need for cardiac valve replacement options capable of growing and remodeling with pediatric patients. We propose a strategy for the storage of living allogenic valves (LAVs) with preserved viability and growth capacity. During storage, LAVs can be rehabilitated using biological, chemical, immunological and mechanical stimuli to increase their availability, viability, durability and growth potential.
Methods: Porcine (N>2) pulmonary roots are dissected, sterilized in a clinically-informed antibiotic cocktail, and incubated in a customized preservation solution for long-term storage. Elements monitored throughout storage include whole-tissue viability, glucose uptake, tissue mechanical properties, and gross and histologic assessments of tissue architecture. A pump-less bioreactor was custom-designed to stimulate physiologic valve open/close cycles and unidirectional flow through the valve, thereby creating a biomimetic biochemical, immunomodulatory and mechanical environment for storage and rehabilitation.
Results: Static storage in preservation solution maintains leaflet viability after 2 weeks (Alamar blue whole-tissue viability assay). Following 1 week of static culture, leaflet alpha smooth muscle actin expression is preserved relative to fresh controls. Ongoing work includes studying the effects of mechanical stimulation, temperature, and oxygen supplementation, as well as metabolic aids, anti-apoptotic molecules, and immunomodulatory agents.
Conclusions: LAVs can be kept viable in storage, providing an off-the-shelf living valve replacement option. The potential to improve viability following preservation may enable the rehabilitation of homografts from deceased donors, significantly increasing LAVs' availability. 
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