Dual Burst and Sustained Release of p-Coumaric Acid from Shape Memory Polymer Foams for Polymicrobial Infection Prevention in Trauma-Related Hemorrhagic Wounds

Abstract

Hemorrhage is the primary cause of trauma-related death. Of patients that survive, polymicrobial infection occurs in 39% of traumatic wounds within a week of injury. Moreover, traumatic wounds are susceptible to hospital-acquired and drug-resistant bacterial infections. Thus, hemostatic dressings with antimicrobial properties could reduce morbidity and mortality to enhance traumatic wound healing. To that end, p-coumaric acid (PCA) was incorporated into hemostatic shape memory polymer foams by two mechanisms (chemical and physical) to produce dual PCA (DPCA) foams. DPCA foams demonstrated excellent antimicrobial and antibiofilm properties against native Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis; co-cultures of E. coli and S. aureus; and drug-resistant S. aureus and S. epidermidis at short (1 h) and long (7 days) time points. Resistance against biofilm formation on the sample surfaces was also observed. In ex vivo experiments in a porcine skin wound model, DPCA foams exhibited similarly high antimicrobial properties as those observed in vitro, indicating that PCA was released from the DPCA foam to successfully inhibit bacterial growth. DPCA foams consistently showed improved antimicrobial properties relative to those of clinical control foams containing silver nanoparticles (AgNPs) against single and mixed species bacteria, single and mixed species biofilms, and bacteria in the ex vivo wound model. This system could allow for physically incorporated PCA to first be released into traumatic wounds directly after application for instant wound disinfection. Then, more tightly tethered PCA can be continuously released into the wound for up to 7 days to kill additional bacteria and protect against biofilms.

Burst Release from In Situ Forming PLGA-Based Implants: 12 Effectors and Ways of Correction

“…In a study by Du C. et al, the design of the experiment to create a new antimicrobial agent for chronic recurrent bacterial infections determined the need for both short-term action of the drug (due to “burst release in the first 18 h”) and long-term action over 7 days [ 85 ].…”

Chitosan Poly(vinyl alcohol) Methacrylate Hydrogels for Tissue Engineering Scaffolds

“…Samples were then washed in PBS at 37 °C for 24 h to wash out any unreacted byproducts. Samples were air-dried overnight and placed into vacuum oven for 24 h before being sterilized by UV light exposure for 1 h before starting the antimicrobial experiment …”