Development of a Geometrically-Tunable Shunt for Pediatric Heart Reconstruction

Introduction: Congenital heart defects (CHDs) are among the top eight causes of infant mortality worldwide. Annually, CHDs affect more than 40,000 babies in the United States, with one in four having a critical CHD that requires surgical intervention within the first year of life. In the most severe cases, infants are born with only half of their heart fully functional and undergo immediate life-saving heart reconstruction surgery. The current procedure involves the implantation of a fixed diameter cardiovascular shunt to divert the blood from the aorta to the lungs. While procedural modifications have improved patient prognosis, mortality rates remain among the highest in cardiothoracic surgery and have failed to improve substantially since the procedure was developed over thirty years ago. A primary limitation is the shunt’s inability to accommodate the physiological changes associated with infant growth, leading to the need for repeated invasive surgery to implant a larger shunt. Computational modeling has previously determined that a 15-18% inner lumen diameter increase is required to accommodate infant growth, in line with clinical observations. Here, we develop a geometrically tunable blood shunt that can increase in diameter on demand to meet these needs, providing clinicians with the unique ability to precisely tune blood flow in proportion to infant growth.

Materials and

Methods: The ability of the shunt to change its lumen diameter is accomplished by adhering a photoresponsive methacrylated dextran (DexMA) hydrogel capable of volume change upon light exposure to the inner surface of a polytetrafluoroethylene (PTFE) tube. 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 volume were achieved by photopolymerization (3mM LAP photoinitiator, λ=400-500nm, 1mW/cm2). Hydrogel volume and moduli were assessed before and after light exposure. In vitro cytocompatibility was assessed monitoring the proliferation of both 3T3 fibroblasts and HUVECs (CCK8), inflammatory response (RAW-Blue macrophage reporter cell line), and hemolysis (ASTM 756-13). To enable hydrogel adhesion to PTFE tubing, a polydopamine (PDA) coating was applied. Coating conditions were optimized, including for coating time (12 hr), concentration (4 mM), and number of coatings (4). Annular prototypes (3.5 mm inner diameter, corresponding to those most commonly used in clinic) were produced and irradiated via a fiberoptic cylindrical light diffuser to examine changes in lumen diameter. Prototype stability and the ability to modify lumen diameter at later timepoints was examined over a one-month period; Irradiation was performed to target 15-18% increase after one week,10% increase per week, or 40% increase after three weeks. Lumen diameter was quantified in ImageJ.

Results, Conclusions, and Discussions: This study investigated the effect of additive crosslink density on the geometric tunability and mechanical properties of hydrogels for biomedical implants. Dithiothreitol (DTT) was employed for crosslinking to intentionally preserve methacrylate groups for subsequent photopolymerization, allowing for hydrogel de-swelling. Low (20%) DTT/methacrylate ratios resulted in larger volume changes, but their use was limited by low moduli. In contrast, high (50%) DTT/methacrylate ratios exhibited minimal volume changes (Fig. 1B-C). To balance geometric control and mechanical stability, an intermediate (40%) ratio was chosen for prototype development. Hydrogels demonstrated excellent cytocompatibility and did not cause adverse effect 3T3 fibroblast or HUVEC proliferation. Macrophage inflammatory activation was comparable to negative (polystyrene) controls. Hemolysis was likewise comparable to non-hemolytic controls (LDPE) and within regulatory standards (5%). By irradiation with a catheter-introducible light source, clinically-indicated increases in lumen diameter (15-18%) necessary to support infant growth occurred within 40-50 seconds, while changes exceeding 30% were attainable (Fig. 1D-E). Lumen diameters remained constant throughout the 28-day period, demonstrating sustained responsiveness of the hydrogels (Fig. 1F). Our findings demonstrate the capability to modulate the inner lumen diameter in a controlled manner to suit personalized medicine requirements. Achievable diameter increases from 15-18% after one week to 40% after three weeks, with an option for intermediate weekly increments of 10% (Fig. 1G-I), highlights the precise control over geometric modifications. The ability to change both the magnitude and timing paves the way for the development of more precise and individualized treatment strategies. This two-stage crosslinking strategy provides a promising approach for developing responsive biomedical implants that can adapt to changing patient requirements. Geometrically tunable pediatric shunts have the potential to reduce the number of invasive surgeries in neonates, leading to improved patient outcomes for this vulnerable population.

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