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

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.

Shape Memory Polymer Foams with Tunable Degradation Profiles.

Uncontrolled hemorrhage is the leading cause of preventable death on the battlefield and results in ∼1.5 million deaths each year. The primary current treatment options are gauze and/or tourniquets, which are ineffective for up to 80% of wounds. Additionally, most hemostatic materials must be removed from the patient within <12 h, which limits their applicability in remote scenarios and can cause additional bleeding upon removal. Here, degradable shape memory polymer (SMP) foams were synthesized to overcome these limitations. SMP foams were modified with oxidatively labile ether groups and hydrolytically labile ester groups to degrade after implantation. Foam physical, thermal, and shape memory properties were assessed along with cytocompatibility and blood interactions. Degradation profiles were obtained in vitro in oxidative and hydrolytic media (3% H2O2 (oxidation) and 0.1 M NaOH (hydrolysis) at 37 °C). The resulting foams had tunable, clinically relevant degradation rates, with complete mass loss within 30-60 days. These SMP foams have potential to provide an easy-to-use, shape-filling hemostatic dressing that can be left in place during traumatic wound healing with future potential use in regenerative medicine applications.

An Evaluation of Sharp Interface Models for CO2 -Brine Displacement in Aquifers.

Understanding multiphase transport within saline aquifers is necessary for safe and efficient CO2 sequestration. To that end, numerous full-physics codes exist for rigorously modeling multiphase flow within porous and permeable rock formations. High-fidelity simulation with such codes is data- and computation-intensive, and may not be suitable for screening-level calculations. Alternatively, under conditions of vertical equilibrium, a class of sharp-interface models result in simplified relationships that can be solved with limited computing resources and geologic/fluidic data. In this study, the sharp-interface model of Nordbotten and Celia (2006a,2006b) is evaluated against results from a commercial full-physics simulator for a semi-confined system with vertical permeability heterogeneity. In general, significant differences were observed between the simulator and the sharp-interface model results. A variety of adjustments were made to the sharp-interface model including modifications to the fluid saturation and effective viscosity in the two-phase region behind the CO2 -brine interface. These adaptations significantly improved the predictive ability of the sharp interface model while maintaining overall tractability.