Infants and children born with severe cardiac valve lesions have no effective long term treatment options since currently available tissue or mechanical prosthetic valves have sizing limitations and no avenue to accommodate the growth of the pediatric patient. Tissue engineered heart valves (TEHVs) which could provide for growth, self-repair, infection resistance, and long-term replacement could be an ideal solution. Porcine small intestinal submucosa (PSIS) has recently emerged as a potentially attractive bioscaffold for TEHVs. PSIS may possess the ability to recruit endogenous cardiovascular cells, leading to phenotypically-matched replacement tissue when the scaffold has completely degraded. Our group has successfully implanted custom-made PSIS valves in 4 infants with critical valve defects in whom standard bioprosthetic or mechanical valves were not an option. Short term clinical follow-up has been promising. However, no hydrodynamic data has been reported to date on these valves. The purpose of this study was to assess the functional effectiveness of tri-leaflet PSIS bioscaffolds in the aortic position compared to standard tri-leaflet porcine bioprosthetic valves. Hydrodynamic evaluation of acute PSIS function was conducted using a left heart simulator in our laboratory. Our results demonstrated similar flow and pressure profiles (p > 0.05) between the PSIS valves and the control valves. However, forward flow energy losses were found to be significantly greater (p < 0.05) in the PSIS valves compared to the controls possibly as a result of stiffer material properties of PSIS relative to glutaraldehyde-fixed porcine valve tissue. Our findings suggest that optimization of valve dimensions and shape may be important in accelerating de novo valve tissue growth and avoidance of long-term complications associated with higher energy losses (e.g. left ventricular hypertrophy). Furthermore, long term animal and clinical studies will be needed in order to conclusively address somatic growth potential of PSIS valves.

Newly developed elastomer heart valves have been shown to better re-create the flow physics of native heart valves, resulting in preferable hemodynamic responses. This emergence has been motivated in part by the recent introduction of percutaneous valve approaches in the clinic. Unfortunately, elastomers such as silicone are prone to structural failure, which drastically limits their applicability the development of a valve prosthesis. To produce a mechanically more robust silicone substrate, we reinforced it with graphene nanoplatelets (GNPs). The nanoplatelets were introduced into a two-part silicone mixture and allowed to cure. Cytotoxicity and hemocompatibility tests revealed that the incorporation of GNPs did not adversely affect cell proliferation or augment adhesion of platelets on the surface of the composite materials. Static mechanical characterization by loading in the tensile direction subsequently showed no observable effect when graphene was utilized. However, cyclic tensile testing (0.05 Hz) demonstrated that silicone samples containing 250 mg graphene/L of uncured silicone significantly improved (p<0.05) material fatigue properties compared with silicone-only controls. This finding suggests that for the silicone-graphene composite, static loads were principally transferred onto the matrix. On the other hand, in cyclic loading conditions, the GNPs were recruited effectively to delay failure of the bulk material. We conclude that application of GNPs to extend silicone durability is useful and warrants further evaluation at the trileaflet valve configuration.

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