Photoresponsive Hydrogels Enable Geometrically Tunable Blood Shunts for Pediatric Use
Wednesday, May 25, 2022
11:00 AM-1:00 PM
BIOMED Master's Thesis Defense
Title:
Photoresponsive Hydrogels Enable Geometrically Tunable Blood Shunts for Pediatric Use
Speaker:
Victor Mishin, Master's Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisors:
Christopher B. Rodell, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Amy L. Throckmorton, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Abstract:
Blood shunts are fixed-diameter tubes, commonly used in heart reconstruction surgeries, including for the treatment of congenital cardiovascular defects. For children born with severe heart defects, such as hypoplastic left heart syndrome, the implantation of a shunt connecting the right subclavian artery and the pulmonary artery allows for single ventricle circulatory support. This life saving procedure is required in the first days of life. However, postoperative mortality rates remain high despite decades of treatment optimization; this is because current shunts are unable to provide increasing blood flow as the infant grows. Here, we develop a geometrically tunable blood shunt that can grow with the child on demand, allowing for increased blood flow through the inner lumen. The ability of the shunt to change in diameter is afforded by affixing a coating of dextran methacrylate (DexMA) hydrogel to the interior surface of the polytetrafluoroethylene (PTFE) tubing; the interior lumen is expanded by additional hydrogel crosslinking.
To optimize hydrogel contraction, DexMA was synthesized with a range of methacrylate substitutions (10% to 95%). The modified DexMA polymers were subject to mechanical testing to optimize crosslinking conditions (i.e., photoinitiator concentration, light exposure times, and light intensities). A two-step photocrosslinking process (λ=500nm, 1mW/cm2, 1mM LAP photoinitiator) was developed to i) cast the hydrogel while retaining vinyl groups and ii) induce contraction via secondary curing. Alternatively, the initial casting step was replaced with a dithiol-mediated crosslinking scheme to retain a known concentration of photoresponsive methacrylate groups. Volumetric decreases during curing were dependent on photoinitiator concentration, polymer modification, concentration, and the duration of light exposure. Optimization of these conditions in both crosslinking approaches enabled >20% reduction in hydrogel volume.
A three-month degradation study revealed the formed hydrogels to be stable throughout the intended period of implantation in clinical scenarios with minimal dependence on hydrogel formulation. Additionally, the DexMA polymers and formed hydrogels were shown to minimally impact cell viability, to have favorable non-immunogenic profiles, and were non-hemolytic according to ASTM F756. For hydrogel coating of the hydrophobic PTFE surface, a polydopamine surface modification was applied and treated by dithiothreitol to provide for Michael-addition with the DexMA hydrogel. The staged crosslinking approaches developed are a promising avenue to create responsive biomedical implants that can grow with pediatric patients.
Contact Information
Natalia Broz
njb33@drexel.edu