Hemostatic shape memory polymer foams with improved survival in a lethal traumatic hemorrhage model.

Although there are many hemostatic agents available for use on the battlefield, uncontrolled hemorrhage is still the primary cause of preventable death. Current hemostatic dressings include QuikClot® Combat Gauze (QCCG) and XStat®, which have inadequate success in reducing mortality. To address this need, a new hemostatic material was developed using shape memory polymer (SMP) foams, which demonstrate biocompatibility, rapid clotting, and shape recovery to fill the wound site. SMP foam hemostatic efficacy was examined in a lethal, noncompressible porcine liver injury model over 6 h following injury. Wounds were packed with SMP foams, XStat, or QCCG and compared in terms of time to bleeding cessation, total blood loss, and animal survival. The hemostatic material properties and in vitro blood interactions were also characterized. SMP foams decreased blood loss and active bleeding time in comparison with XStat and QCCG. Most importantly, SMP foams increased the 6 h survival rate by 50% and 37% (vs. XStat and QCCG, respectively) with significant increases in survival times. Based upon in vitro characterizations, this result is attributed to the low stiffness and shape filling capabilities of SMP foams. This study demonstrates that SMP foams have promise for improving upon current clinically available hemostatic dressings and that hemostatic material properties are important to consider in designing devices for noncompressible bleeding control. STATEMENT OF SIGNIFICANCE: Uncontrolled hemorrhage is the leading cause of preventable death on the battlefield, and it accounts for approximately 1.5 million deaths each year. New biomaterials are required for improved hemorrhage control, particularly in noncompressible wounds in the torso. Here, we compared shape memory polymer (SMP) foams with two clinical dressings, QuikClot Combat Gauze and XStat, in a pig model of lethal liver injury. SMP foam treatment reduced bleeding times and blood loss and significantly improved animal survival. After further material characterization, we determined that the improved outcomes with SMP foams are likely due to their low stiffness and controlled shape change after implantation, which enabled their delivery to the liver injuries without inducing further wound tearing. Overall, SMP foams provide a promising option for hemorrhage control.

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.

Validity, reliability and minimal detectable change of the balance evaluation systems test (BESTest), mini-BESTest and brief-BESTest in patients with end-stage renal disease.

PURPOSE: This study determined the validity, test-retest reliability and minimal detectable change of the balance evaluation systems test (BESTest), mini-balance evaluation systems test (Mini-BESTest) and brief-balance evaluation systems test (Brief-BESTest) in patients with end-stage renal disease. METHODS: A cross-sectional study with 74 patients with end-stage renal disease (male 66.2%; 63.9 ± 15.1 years old) was conducted. Participants were asked to report the number of falls during the previous 12 months and to complete the activity-specific balance confidence (ABC) scale. The BESTest was administered, and the Mini-BESTest and Brief-BESTest scores were computed based on the BESTest performance. Validity was assessed by correlating balance tests with each other and with the ABC scale. Test-retest relative reliability and agreement were explored with the intraclass correlation coefficient (ICC) equation (2,1) and the Bland and Altman method. Minimal detectable changes at the 95% confidence level were established. RESULTS: Balance test scores were significantly correlated with each other (spearman's correlation = 0.89-0.92) and with the ABC scale (spearman's correlation = 0.49-0.59). Balance tests presented high test-retest reliability (ICC = 0.84-0.94), with no evidence of bias. Minimal detectable change values were 10.8 (expressed as a percentage 13.5%), 5.3 (23.7%) and 5.6 (34%) points for the BESTest, Mini-BESTest and Brief-BESTest, respectively. CONCLUSIONS: All tests are valid and reliable to assess balance in patients with end-stage renal disease. Nevertheless, based on the minimal detectable changes found, BESTest and Mini-BESTest may be the most recommended tests for this specific population. Implications for Rehabilitation Balance evaluation systems test (BESTest), mini-balance evaluation systems test (Mini-BESTest) and brief-balance evaluation systems test (Brief-BESTest) are reliable and valid in patients with end stage renal disease (ESRD). The minimal detectable changes of 10.8 for the BESTest, 5.3 for the Mini-BESTest and 5.6 for the Brief-BESTest can be used by clinicians to identify a true change in balance over time or in response to interventions. Based on the minimal detectable changes found, BESTest and Mini-BESTest may be the most recommended; and the selection of one of them may be based on time and equipment availability.