SHAPE MEMORY POLYMER HYDROGEL FOAMS FOR FISTULA CLOSURE

Abstract

Abstract Introduction Crohn’s disease can lead to fistula formation between portions of the urinary, reproductive, and digestive systems. The abnormal connections caused by these tunneling sores cause severe pain, infections, and abscess formation. Currently, 83% of Crohn’s patients with fistula formation undergo surgical intervention to either drain or bypass the fistula openings, and ~23% of these patients ultimately require bowel resections. To address this clinical need, we propose to synthesize a shape memory polymer (SMP) hydrogel foam system for fistula closure and healing. SMP foams are porous materials that can be heated and compressed into a low-profile geometry that is retained after cooling. This shape enables minimally invasive delivery (i.e. via catheter) to a fistula site. Once the foams are heated to body temperature, they expand back to their original shape to conform to the implantation site geometry. Here, we present a degradable SMP hydrogel foam with antimicrobial and antioxidant phenolic acids for potential use as a fistula closure scaffold. Methods Foams were synthesized with 3-arm and linear poly(ethylene glycol) (PEG), amylopectin/pullulan, and phenolic acids in combination with hexamethylene diisocyanate in the presence of surfactants, catalysts, and foam blowing agents to form a hydrophilic, chemically crosslinked foam. Resulting foams were characterized in terms of swelling ratios, pore sizes, glass transition temperatures, and shape recovery. Degradation profiles were characterized in glucoamylase. Antimicrobial efficacy against E. coli was measured by quantifying colony forming units of bacteria following exposure to SMP hydrogels. Antioxidant properties were assessed in the presence of hydrogen peroxide. Results SMP hydrogel swelling ratio, stiffness, shape memory properties are tuned by altering monomer ratios and lengths and foaming conditions. In preliminary degradation studies in glucoamylase, degradation rates are dependent upon starch content; increased degradation is observe with increase pullalan content, Figure 1. Phenolic acid-containing SMP foams exhibit antimicrobial efficacy against E. coli and antioxidant properties in hydrogen peroxide. Conclusions Current studies include full material characterization of the library of synthesized hydrogels and longer-term degradation analysis. This system can be further built upon in future studies to include a drug-delivery component. Overall, SMP hydrogel foams present a highly tunable platform material that can be modified with required functionalities to promote fistula closure.