Discipline: Biological Sciences
Subcategory: Biomedical Engineering
Room: Exhibit Hall
Sapaydia Kaylani Rosales - University of South Carolina
Co-Author(s): Dr. Henry Beaman, Syracuse University, NY; Dr. Mary Beth Monroe, Syracuse University, NY
Crohn’s disease is the most common type of inflammatory bowel disease, affecting ~1 million people in the US and Europe alone. Nearly 35% of patients will develop fistulas, or abnormal pathways between sections of the digestive tract, during their disease progression. Several treatment options are available (e.g., setons and fistula fillers), however, these options may lead to infections or dislodgement of the filler. Shape memory polymer (SMP) hydrogels are a candidate for new fistula plugs; however, current formulations exhibit a slow degradation rate relative to fistula wound healing.Diisocyanates react with the hydroxyl groups on disulfide-containing monomers needed in SMP polymers to enable degradation. We hypothesize that adjusting the diisocyanate chemistry would enable tuning SMP hydrogel properties, including degradation rates. Four diisocyanates were used to test this theory: hexamethylene diisocyanate (HDI), butane diisocyanate (BDI), methylene diphenyl diisocyanate (MDI), and trimethyl hexamethylene diisocyanate (TMHDI). After synthesis, SMP hydrogels were characterized in terms of swelling ratio, gel fraction, stiffness, shape fixity and recovery, and surface structures. Degradation was assessed in a 10 mM dithiothreitol (DTT) and 10 mM glutathione solution. All results were analyzed using students’ T-tests to determine statistical differences.BDI hydrogels exhibited the highest swelling ratio (2.24) and TMHDI hydrogels had the highest gel fraction (89%). Tensile and compressive testing revealed that MDI integration resulted in a significantly higher Young’s Modulus (8% and 164% kPa, respectively). Scanning electron micrograph images displayed non-uniform pore sizes between each foam, which is attributed to altered crosslink density. Shape recovery and fixity confirmed that HDI had higher recovery (94%) and TMHDI had higher fixity (108%). Accelerated degradation in 10 mM DTT resulted in full degradation of BDI and TMHDI by Day 2, with MDI and HDI having 53% and 27% mass remaining by Day 26, respectively. In the non-accelerated 10 mM glutathione media, HDI, MDI, BDI, and TMHDI had 66%, 90%, 59%, and 61% mass remaining by Day 21, respectively. Faster degradation of BDI is attributed to the hydrophilic nature of the diisocyanate’s short carbon chain while the degradation of TMHDI is attributed to increased chain flexibility from pendant methyl groups.Varying the diisocyanate resulted in tunable degradation properties of SMP hydrogels. Future studies may consider combining diisocyanates to further tune degradation rates. These hydrogels could provide a biodegradable fistula filler to improve on current treatments.References: Beaman, H., Howes, B., Ganesh, P., & Monroe, M.B. 2022. Shape memory polymer hydrogels with cell-responsive degradation mechanisms for Crohn’s fistula closure. J Biomed Mater Res., 110(7), 1329-1340.Levy, C. & Tremaine, W. 2002. Management of internal fistulas in Crohn’s Disease. Inflamm Bowel Dis., 8(2), 106-111.
Funder Acknowledgement(s): Thank you to the NSF, Crohn's and Colitis Foundation, the Interactive Biomaterials Program, and the Syracuse University STEM Fellowship for the funding to make this research possible.
Faculty Advisor: Dr. Mary Beth Monroe, email@example.com
Role: My contribution to this research involves the synthesis of the SMP hydrogel films and foams and diisocyanate crosslinkers, characterization of these hydrogels (welling ratio, gel fraction, stiffness testing, foam surface morphology, and shape fixity and recovery), and beginning the accelerated and non-accelerated degradation studies.