Growth of Tissue-Engineered Vascular Grafts and Heart Valves As Pediatric Conduits.

Background: Growth is the Holy Grail of tissue implants in pediatrics, yet the outcomes from a small but increasing number of studies have not been assessed using metrics of growth. Methods: A systematic review was conducted to identify preclinical and pediatric clinical trials of implanted vascular grafts and heart valves, indicating growth of the implant based on a proposed definition of functional regenerative growth: increases in critical physical dimension(s) by increases in tissue mass with maintenance of required function. Results: Five distinct approaches, distinguished by scaffold type and use of preseeded cells, were identified among studies reported for tissue-engineered vascular grafts (TEVGs) and heart valves (TEHVs), with 2 of these approaches being used for both indications. A total of 11 publications were selected for data tabulation. For TEVGs, increases in length are reported across all studies (14%-130%), whereas diameter change (-38% to +89%) varied with anatomical location. For TEHVs, increases of diameter consistent with somatic growth have been reported for 4 different biologic valves (12%-78%) across preclinical studies. Commensurate leaflet growth has not been clearly established. Conclusions: Growth capacity of TEVGs has been established in preclinical studies for multiple approaches, including some proceeding to clinical trials. For TEHVs, increases in the diameter are reported for several approaches in preclinical studies, but limited evidence exists to date for leaflet growth. TEVGs and TEHVs have both demonstrated potential for growth and, thus, improved clinical outcomes compared with current implants that have no growth capacity.