In vitro and in vivo degradation correlations for polyurethane foams with tunable degradation rates.

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 foams with tunable interconnectivity using off-the-shelf foaming components.

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.

Biostable Shape Memory Polymer Foams for Smart Biomaterial 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.

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.