Lan Ziyang, Guo Leopold, Fletcher Alan, Ang Nicolai, Whitfield-Cargile Canaan, Bryan Laura, Welch Shannara, Richardson Lauren, Cosgriff-Hernandez Elizabeth
Department of Biomedical Engineering, the University of Texas at Austin, Austin, TX, 78712, USA.
Department of Large Animal Medicine, University of Georgia, Athens, GA, 30602, USA.
Bioact Mater. 2024 Sep 10;42:433-448. doi: 10.1016/j.bioactmat.2024.08.044. eCollection 2024 Dec.
Effective treatment of infection in chronic wounds is critical to improve patient outcomes and prevent severe complications, including systemic infections, increased morbidity, and amputations. Current treatments, including antibiotic administration and antimicrobial dressings, are challenged by the increasing prevalence of antibiotic resistance and patients' sensitivity to the delivered agents. Previous studies have demonstrated the potential of a new antimicrobial agent, Gallium maltolate (GaM); however, the high burst release from the GaM-loaded hydrogel gauze required frequent dressing changes. To address this need, we developed a hydrogel foam-based wound dressing with GaM-loaded microspheres for sustained infection control. First, the minimal inhibitory and bactericidal concentrations (MIC and MBC) of GaM against two strains isolated from chronic wounds were identified. No significant adverse effects of GaM on dermal fibroblasts were shown at the MIC, indicating an acceptable selectivity index. For the sustained release of GaM, electrospraying was employed to fabricate microspheres with different release kinetics. Systematic investigation of loading and microsphere size on release kinetics indicated that the larger microsphere size and lower GaM loading resulted in a sustained GaM release profile over the target 5 days. Evaluation of the GaM-loaded hydrogel dressing demonstrated cytocompatibility and antibacterial activities with a zone of inhibition test. An equine distal limb wound model was developed and utilized to demonstrate the efficacy of GaM-loaded hydrogel foam . This antimicrobial hydrogel foam dressing displayed the potential to combat methicillin-resistant (MRSA) infection with controlled GaM release to improve chronic wound healing.
有效治疗慢性伤口感染对于改善患者预后和预防严重并发症至关重要，这些并发症包括全身感染、发病率增加和截肢。目前的治疗方法，包括抗生素给药和抗菌敷料，正面临着抗生素耐药性日益普遍以及患者对所使用药物敏感性的挑战。先前的研究已经证明了一种新型抗菌剂——麦芽酚镓（GaM）的潜力；然而，负载GaM的水凝胶纱布的高突释需要频繁更换敷料。为了满足这一需求，我们开发了一种基于水凝胶泡沫的伤口敷料，其中含有负载GaM的微球，用于持续控制感染。首先，确定了GaM对从慢性伤口分离出的两种菌株的最低抑菌浓度和最低杀菌浓度（MIC和MBC）。在MIC浓度下，未显示GaM对真皮成纤维细胞有明显的不良反应，表明其选择性指数可接受。为了实现GaM的持续释放，采用电喷雾法制备了具有不同释放动力学的微球。对负载量和微球尺寸对释放动力学的系统研究表明，较大的微球尺寸和较低的GaM负载量导致在目标5天内GaM呈现持续释放曲线。通过抑菌圈试验评估负载GaM的水凝胶敷料的细胞相容性和抗菌活性。建立并利用马远端肢体伤口模型来证明负载GaM的水凝胶泡沫的疗效。这种抗菌水凝胶泡沫敷料显示出在控制GaM释放以改善慢性伤口愈合方面对抗耐甲氧西林金黄色葡萄球菌（MRSA）感染的潜力。
