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% H 2 O 2 (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.

Polyurethane foams provide a wide range of applications as a biomaterial system due to the ability to tune their physical, chemical, and biological properties to meet the requirements of the intended applications. Another key parameter that determines the usability of this biomaterial is its degradability under body conditions. Several current approaches focus on slowing the degradation rate for applications that require the implant to be present for a longer time frame (over 100 days). Here, biostable shape memory polymer (SMP) foams were synthesized with added ether-containing monomers to tune the degradation rates. The physical, thermal and shape memory properties of these foams were characterized along with their cytocompatibility and blood interactions. Degradation profiles were assessed in vitro in oxidative (3% H2O2; real-time) and hydrolytic media (0.1 M NaOH; accelerated) at 37 °C. The resulting foams had tunable degradation rates, with up 15% mass remaining after 108 days, and controlled erosion profiles. These easy-to-use, shape-filling SMP foams have the potential for various biomaterial applications where longer-term stability without the need for implant removal is desired.

Repeated use of intravenous infusions to deliver drugs can cause nerve damage, pain, and infection. There is an unmet need for a drug delivery method that administers drugs on demand for prolonged use. Here, we developed magnetically responsive shape memory polymers (SMPs) to enhance control over drug release. Iron oxide magnetic nanoparticles (mnps) were synthesized and incorporated into previously developed SMPs to enable magnetically induced shape memory effects that can be activated remotely via the application of an alternating magnetic field. These materials were tested for their shape memory properties (dynamic mechanical analysis), cytocompatibility (3T3 fibroblast viability), and tunable drug delivery rates (UV–VIS to evaluate the release of incorporated doxorubicin, 6-mercaptopurine, and/or rhodamine). All polymer composites had >75% cytocompatibility over 72 h. Altering the polymer chemistry and mnp content provided methods to tune drug release. Namely, linear polymers with higher mnp content had faster drug release. Highly cross-linked polymer networks with lower mnp content slowed drug release. Shape memory properties and polymer/drug interactions provided additional variables to tune drug delivery rates. Polymers that were fixed in a strained secondary shape had a slower release rate compared with unstrained polymers, and hydrophobic drugs were released more slowly than hydrophilic drugs. Using these design principles, a single material with gradient chemistry and dual drug loading was synthesized, which provided a unique mechanism to deliver two drugs from a single scaffold with distinct delivery profiles. This system could be employed in future work to provide controlled release of selected drug combinations with enhanced control over release as compared with previous approaches.

Chronic wounds can remain open for several months and have high risks of amputation due to infection. Dressing materials to treat chronic wounds should be conformable for irregular wound geometries, maintain a moist wound bed, and reduce infection risks. To that end, we developed cytocompatible shape memory polyurethane-based poly­(ethylene glycol) (PEG) hydrogels that allow facile delivery to the wound site. Plant-based phenolic acids were physically incorporated onto the hydrogel scaffolds to provide antimicrobial properties. These materials were tested to confirm their shape memory properties, cytocompatibility, and antibacterial properties. The incorporation of phenolic acids provides a new mechanism for tuning intermolecular bonding in the hydrogels and corollary mechanical and shape memory properties. Phenolic acid-containing hydrogels demonstrated an increased shape recovery ratio (1.35× higher than the control formulation), and materials with cytocompatibility >90% were identified. Antimicrobial properties were retained over 20 days in hydrogels with higher phenolic acid content. Phenolic acid retention and antimicrobial efficacy were dependent upon phenolic acid structures and interactions with the polymer backbone. This novel hydrogel system provides a platform for future development as a chronic wound dressing material that is easy to implant and reduces infection risks.

Polyurethane foams present a tunable biomaterial platform with potential for use in a range of regenerative medicine applications. Achieving a balance between scaffold degradation rates and tissue ingrowth is vital for successful wound healing, and significant in vivo testing is required to understand these processes. Vigorous in vitro testing can minimize the number of animals that are required to gather reliable data; however, it is difficult to accurately select in vitro degradation conditions that can effectively mimic in vivo results. To that end, we performed a comprehensive in vitro assessment of the degradation of porous shape memory polyurethane foams with tunable degradation rates using varying concentrations of hydrogen peroxide to identify the medium that closely mimics measured in vivo degradation rates. Material degradation was studied over 12 weeks in vitro in 1%, 2%, or 3% hydrogen peroxide and in vivo in subcutaneous pockets in Sprague Dawley rats. We found that the in vitro degradation conditions that best predicted in vivo degradation rates varied based on the number of mechanisms by which the polymer degraded and the polymer hydrophilicity. Namely, more hydrophilic materials that degrade by both hydrolysis and oxidation require lower concentrations of hydrogen peroxide (1%) to mimic in vivo rates, while more hydrophobic scaffolds that degrade by oxidation alone require higher concentrations of hydrogen peroxide (3%) to model in vivo degradation. This information can be used to rationally select in vitro degradation conditions that accurately identify in vivo degradation rates prior to characterization in an animal model.

Shape memory polymer foam hemostats are a promising option for future hemorrhage control in battlefield wounds. To enable their use as hemostatic devices, they must be optimized in terms of formulation and architecture, and their safety and efficacy must be characterized in animal models. Relevant in vitro models can be used for device optimization to help mitigate the excess use of animals and reduce costs of clinical translation. In this work, a simplified gunshot wound model and a grade V liver injury model were constructed. The models were used to characterize the effects of shape memory polymer foam hemostat geometry on wall pressures, application/removal times, hemorrhage (fluid loss), and fluid absorption in comparison with clinical controls. It was found that there is no benefit in over‐sizing the hemostatic device relative to wound volume and that geometry effects are dependent upon the wound type. These models provide a rapid means for elucidation of promising hemostat geometries and formulations for use in future in vivo testing.

The ability to easily and safety tune pore structures of gas-blown polyurethane shape memory polymer (SMP) foams could improve their outcomes as hemostatic dressings or tissue engineering scaffolds and enable overall commercialization efforts. Incorporating physical blowing agents into the polymer mix can be used to tune pore size and interconnectivity without altering foam chemistry. Enovate (HFC-254fa) is a commonly used physical blowing agent in gas-blown foams, but the Environmental Protection Agency (EPA) considers its use unacceptable because it is a hydrofluorocarbon that contributes to global warming. Here, off-the-shelf solvents accepted for use by the EPA, acetone, dimethyoxymethane (methylal), and methyl formate, were used as physical blowing agents by adding small volumes during foam fabrication.Increasing the physical blowing agent volume resulted in greater pore interconnectivity while maintaining SMP foam chemical and thermal properties. Pore size and interconnectivity also impacted cell and blood interactions with the foams. This work provides a safe and easy method for tuning SMP foam interconnectivity to aid in future commercialization efforts in a range of potential biomedical applications.

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.