Vanillic Acid-based Pro-coagulant Hemostatic Shape Memory Polymer Foams with Antimicrobial Properties against Drug-resistant Bacteria

Uncontrolled bleeding is the primary cause of trauma-related death. For patients that are brought to the hospital in time to receive treatment, there is a great risk of contracting drug-resistant bacterial wound infections. Therefore, low-cost hemostatic agents with procoagulant and antibacterial properties are essential to reduce morbidity and mortality in patients with traumatic wounds. To that end, we introduced vanillic acid (VA) into shape memory polymer (SMP) foams through a dual incorporation mechanism to make dual vanillic acid (DVA) foams. The dual mechanism increases VA loading while allowing burst and sustained delivery of VA from foams. DVA foams exhibit antimicrobial and antibiofilm properties against native and drug-resistant Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis. Also, DVA foams inhibit the growth rate of both methicillin-sensitive and -resistant S. aureus colonies to limit their size and promote small colony variants. DVA SMP foams induce primary and secondary hemostasis in in vitro blood interaction studies. As a proof of concept, we demonstrated easy delivery and rapid clotting in a porcine liver injury model, indicating DVA foam feasibility for use as a hemostatic dressing. Thus, the inexpensive production of DVA SMP foams could enable a cost-effective procoagulant hemostatic dressing that is resistant to bacterial colonization to improve short- and long-term outcomes for hemorrhage control in traumatically injured patients. STATEMENT OF SIGNIFICANCE: Uncontrolled bleeding is the primary cause of preventable death on the battlefield. Of patients that survive, ∼40% develop polymicrobial infections within 5 days of injury. Drug-resistant infections are anticipated to cause more deaths than all cancers combined by 2050. Therefore, novel non-drug-based biomaterials strategies for infection control in wound care are increasingly important. To that end, we developed hemostatic polyurethane foams that include antimicrobial and pro-coagulant vanillic acid, a plant-based antimicrobial species. These foams provide excellent protection against native and drug-resistant bacteria and enhanced coagulation while remaining cytocompatible. In a pilot porcine liver injury model, vanillic acid-containing foams stabilized a bleed within <5 minutes. These biomaterials provide a promising solution for both hemorrhage and infection control in wound care.