Abstract
The leading cause of trauma-related death before arrival at a hospital is uncontrolled blood loss. Upon arrival at the hospital, microbial infections in traumatic wounds become an additional factor that increases mortality. The development of hemostatic materials with antimicrobial and antioxidant properties could improve morbidity and mortality in these wounds. To that end, phenolic acids (PAs) were successfully incorporated into the network of shape memory polymer (SMP) polyurethane foams by reacting them with isocyanates. Resulting PA-containing SMP foam shape memory properties, antimicrobial and antioxidant activity, and blood and cell interactions were characterized. Results showed that p-coumaric, vanillic, and ferulic acids were successfully incorporated into the SMP foams. The PA-containing SMP foams retained the antimicrobial and antioxidant properties of the incorporated PAs, with ∼20% H2O2 scavenging and excellent antimicrobial properties again E. coli (∼5X reduction in CFUs vs. control foams), S. aureus (∼4.5X reduction in CFUs vs. control foams, with comparable CFU counts to clinical control), and S. epidermidis (∼25–120X reduction in CFUs vs. control foams, with comparable CFU counts to clinical control). Additionally, appropriate thermal and shape memory properties of PA foams could enable stable storage in low-profile secondary geometries at temperatures up to ∼55°C and rapid expand within ∼2 min after exposure to water in body temperature blood. PA foams had high cytocompatibility (>80%), non-hemolytic properties, and platelet attachment and activation, with improved cytocompatibility and hemocompatibility in comparison with clinical, silver-based controls. The incorporation of PAs provides a natural non-antibiotic approach to antimicrobial SMP foams with antioxidant properties. This system could improve outcomes in traumatic wounds to potentially reduce bleeding-related deaths and subsequent infections.
Highlights
On the battlefield, uncontrolled bleeding is the primary cause of trauma-related mortality
P-coumaric acid (PCA) and 1-ethyl-3-carbodiimide hydrochloride (EDC) were purchased from TCI America Inc. (Portland, United States); ferulic acid (FA), 4-dimethylaminopyridine (DMAP), and vanillic acid were purchased from Alfa Aesar (Haverhill, United States); T-131 and BL-22 were supplied by Evonik (Essen, Germany)
Successful incorporation of phenolic acids (PAs) into the shape memory polymer (SMP) foam was confirmed by surface chemistry analysis using Fourier transform infrared (FTIR) spectroscopy, Figure 2
Summary
On the battlefield, uncontrolled bleeding is the primary cause of trauma-related mortality. Of these deaths, 33–56% occur during the prehospital period. Polymicrobial infections occur in 39% of traumatic wounds within the first week after injury, complicating healing processes in patients who do survive. The primary current treatment for hemorrhage control includes gauze that has been modified with anticoagulants. Combat Gauze (QCCG) is widely used on the battlefield and in hospitals, but its prolonged implantation increases risk of embolism. According to a pig study conducted by OtrockaDomagala et al, when QCCG was left in the wound for more than 24 h, fibrin-gaseous embolic material was found in the pulmonary arteries. Newer clinically-available approaches to bleeding control include
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