Department of Biomedical and Chemical Engineering, Syracuse Biomaterials Institute, and BioInspired Syracuse: Institute for Material and Living Systems, Syracuse University, Syracuse, NY 13244, United States.
Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Acta Biomater. 2024 Nov;189:254-269. doi: 10.1016/j.actbio.2024.09.036. Epub 2024 Sep 27.
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 induced 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 min. These biomaterials provide a promising solution for both hemorrhage and infection control in wound care.
失控性出血是创伤相关死亡的主要原因。对于及时送往医院接受治疗的患者，存在感染耐药性细菌伤口感染的巨大风险。因此，具有促凝和抗菌特性的低成本止血剂对于降低创伤性伤口患者的发病率和死亡率至关重要。为此，我们通过双重掺入机制将香草酸（VA）引入形状记忆聚合物（SMP）泡沫中，制成双重香草酸（DVA）泡沫。双重机制增加了 VA 的负载量，同时允许泡沫中 VA 的爆发和持续释放。DVA 泡沫对原生和耐药金黄色葡萄球菌（S. aureus）和表皮葡萄球菌具有抗菌和抗生物膜特性。此外，DVA 泡沫抑制了耐甲氧西林敏感和耐甲氧西林金黄色葡萄球菌菌落的生长速度，以限制其大小并促进小菌落变体的生长。DVA SMP 泡沫在体外血液相互作用研究中诱导了初级和次级止血。作为概念验证，我们在猪肝损伤模型中证明了易于输送和快速凝血，表明 DVA 泡沫可作为止血敷料使用。因此，DVA SMP 泡沫的低成本生产可以实现一种具有成本效益的促凝止血敷料，该敷料能够抵抗细菌定植，从而改善创伤性出血患者的短期和长期止血效果。
失控性出血是战场上可预防死亡的主要原因。在幸存的患者中，约有 40%的患者在受伤后 5 天内发生多微生物感染。预计到 2050 年，耐药感染导致的死亡人数将超过所有癌症的总和。因此，新型非药物基于生物材料的伤口护理感染控制策略变得越来越重要。为此，我们开发了包含抗菌和促凝香草酸的止血聚氨酯泡沫，香草酸是一种植物来源的抗菌物质。这些泡沫对原生和耐药细菌提供了极好的保护，并增强了凝血作用，同时保持细胞相容性。在猪肝损伤模型的初步研究中，含有香草酸的泡沫在<5 分钟内稳定了出血。这些生物材料为伤口护理中的出血和感染控制提供了有希望的解决方案。
