Development of a Size-Changing Cardiovascular Shunt for Pediatric Heart Reconstruction

Introduction:: More than 40,000 babies in the US are affected by congenital heart defects each year. In the most severe cases, infants are born with only half of their heart fully developed and undergo immediate life-saving heart reconstruction surgery. The procedure requires placement of a fixed-diameter plastic tube to divert blood flow from the aorta to the lungs. While procedural modifications have improved prognosis in recent decades, mortality rates remain high. This is because the shunts are unable to grow with the child, leading to a need for repeated invasive surgery to place a larger shunt. Computational modeling has previously determined that a 15-18% increase in inner lumen diameter is required to accommodate infant growth, in line with clinical observations. Here, we develop a geometrically tunable blood shunt that can change in diameter on demand to meet these needs.

Materials and Methods:: Methacrylated dextran (DexMA) was synthesized via esterification with glycidyl methacrylate (50% substitution). Cylindrical hydrogels (10%_w/v) were formed by addition crosslinking with dithiothreitol (DTT; DTT/methacrylate ratios of 20-50%, Fig. 1A). Subsequent changes in geometry were achieved by photopolymerization (3mM LAP photoinitiator, λ=400-500nm, 1mW/cm²). Hydrogel volume and compressive moduli were assessed before and after light exposure. Biocompatibility with a vascular blood-contacting environment was assessed in vitro, including cytotoxicity (3T3 fibroblasts, PrestoBlue), inflammatory response (RAW-Blue macrophage reporter cell line), and hemolysis (ASTM 756-13). A polydopamine (PDA) coating was applied (4mM, 12hrs, 4 coats) to polytetrafluoroethylene (PTFE), the same material used in commercially-available cardiovascular shunts. Short annular prototypes (5mm length), including a 3.5mm inner lumen were prepared and irradiated via a fiberoptic cylindrical light diffuser to assess changes in lumen diameter.

Results, Conclusions, and Discussions:: Addition crosslinking by DTT was intentionally chosen to preserve unreacted methacrylate groups for subsequent photopolymerization and thereby improve geometric tunability. Accordingly, greatest volume changes were observed with a low DTT/methacrylate ratio; no significant difference was observed between 30% and 40% groups (Fig. 1B). However, the moduli of 20% and 30% hydrogels were low; 40%was comparable to connective tissues; 50% was rigid and brittle post-cure (Fig. 1C). Based on the combination of geometric tunability and mechanical stability, 40% was chosen for prototype development. Hydrogels exhibited good cytocompatibility profiles, with no hinderance on 3T3 proliferation. Macrophages did not adhere to the hydrogel surface or exhibit inflammatory activation, relative to untreated controls. Hemolysis was comparable to non-hemolytic controls (LDPE, PTFE), and within the standard threshold of 5%. For annular prototypes, an increase in inner lumen diameter was observed upon irradiation (Fig. 1D), reaching changes of 15-18% within 40-50 seconds (Fig. 1E). Further changes in geometry were possible, as may be needed in some clinical scenarios. The two-stage crosslinking approach developed herein is a promising strategy to produce responsive biomedical implants that can change in size to accommodate evolving patient needs. The application of geometrically tunable pediatric shunts may reduce the need of repeated open thoracotomy in newborns, potentially improving patient outcomes for this medically fragile population.

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