Development and Characterization of Covalently Crosslinked Hydrogels

Wednesday, May 31, 2023

1:00 PM-3:00 PM

BIOMED Master's Thesis Defense

Title:
Development and Characterization of Covalently Crosslinked Hydrogels for Use in Geometrically Tunable Blood Shunts

Speaker:
Elisabeth Posthill, Master's Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Christopher Rodell, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Children born with severe heart defects such as hypoplastic left heart syndrome, in which the left side of the heart is underdeveloped, require immediate and life-saving open-heart reconstruction surgery within the first few days of life. These reconstructive procedures rely upon implantation of a fixed diameter blood shunt to allow for single ventricle circulatory support. However, postoperative mortality rates remain among the highest in all of cardiothoracic surgery. This is because currently used shunts are unable to increase in diameter and thereby provide an increase in blood flow to the lungs as the child grows. Resulting hypoxia and hemodynamic instability necessitate high risk revision surgeries to implant a shunt of larger diameter. The alternative proposed solution herein is a geometrically tunable blood shunt that can increase in internal diameter on demand, thereby allowing increased blood flow through the shunt. This is accomplished by the application of a dextran methacrylate (DexMA) hydrogel coating on the interior surface of the polytetrafluoroethylene (PTFE) tubing, the current shunt material used in clinic. When exposed to blue light, the hydrogel contracts and therefore expands the inner lumen. Minimally invasive introduction of the blue light via catheterization would eliminate the need for major revision surgeries, thereby reducing mortality risks and improving the quality of life for these children.

The DexMA hydrogels undergo two sequential crosslinking steps to first cast the hydrogels into a solid lining and later cause hydrogel contraction. Previous work had focused on development of a dual-stage photopolymerization, with each step initiated by blue light. However, the approach exhibited a limited range of hydrogel volumetric changes. To improve geometric tunability, here we investigate a dithiol-mediated addition crosslinking scheme for the initial hydrogel casting, intentionally developed to retain light-reactive methacrylates for secondary photopolymerization. Hydrogels of varying formulation (e.g., altered polymer concentration, degree of modification, and dithiol crosslink density) were prepared and subsequently characterized to assess their physical properties (geometric tunability, moduli, and long-term stability). Data were used to identify the optimal hydrogel formulation to enable device performance. These investigations identified mechanically stable hydrogels that were able to achieve >50% change in volume upon blue light exposure. With the addition of a brief photocrosslinking event, hydrogels were stable towards swelling and degradation under physiological conditions over the course of three months, which coincides with the intended period of device implantation. DexMA polymers and formed hydrogels were found to have no impact on cell viability, did not induce an innate inflammatory response, and were non-hemolytic according to ASTM standards. Then employed in shunt prototypes and irradiated via a cylindrical light diffuser, inner diameters of the shunt increased by nearly 30% within minutes – well in excess of the 15-18% change theoretically required to accommodate up to two years of infant growth. DexMA hydrogels formed through addition crosslinking are highly tunable via later photopolymerization, exhibit an excellent biological safety profile, and are a promising approach to generate a size-changing blood shunt for pediatric use.

Contact Information

Natalia Broz
njb33@drexel.edu