Shape memory polymer hydrogels with cell-responsive degradation mechanisms for Crohn's fistula closure

Abstract

Crohn's disease, a form of inflammatory bowel disease, commonly results in fistulas, tunneling wounds between portions of the urinary, reproductive, and/or digestive systems. These tunneling wounds cause pain, infection, and abscess formation. Of Crohn's patients with fistula formation, 83% undergo surgical intervention to either drain or bypass the fistula openings, and ~23% of these patients ultimately require bowel resections. Current treatment options, such as setons, fibrin glues, and bioprosthetic plugs, are prone to infection, dislodging, and/or require a secondary removal surgery. Thus, there is a need for fistula filling material that can be easily and stably implanted and then degraded during fistula healing to eliminate the need for removal. Here, the development of a shape memory polymer hydrogel foam containing polyvinyl alcohol (PVA) and cornstarch (CS) with a disulfide polyurethane crosslinker is presented. These materials undergo controlled degradation by amylase, which is present in the digestive tract, and by reducing thiol species such as glutathione/dithiothreitol. Increasing CS content and using lower molecular weight PVA can be used to increase the degradation rate of the materials while maintaining shape memory properties that could be utilized for easy implantation. This material platform is based on low-cost and easily accessible components and provides a biomaterial scaffold with cell-responsive degradation mechanisms for future potential use in Crohn's fistula treatment.

Keywords: Crohn's disease; hydrogels; shape memory polymer; starch.