Kennewell Tahlia L, Haidari Hanif, Mashtoub Suzanne, Howarth Gordon S, Bennett Catherine, Cooksley Clare M, Wormald Peter John, Cowin Allison J, Vreugde Sarah, Kopecki Zlatko
Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.
School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia.
Materials (Basel). 2024 Feb 7;17(4):793. doi: 10.3390/ma17040793.
is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing cutaneous infection with positive effects observed in the progression of wound healing.
是临床伤口感染中最常见的病原体之一。临床研究表明，该感染会导致伤口面积增大，抑制愈合，且抗菌耐药性普遍存在。先前已证明，壳聚糖 - 葡聚糖水凝胶（Chitogel）中的羟基吡啶酮衍生铁螯合剂去铁酮（Def）和血红素类似物镓原卟啉（GaPP）在体外对PAO1和临床分离株有效。此外，这两种药物的组合已显示可通过快速减少出血和防止粘连来改善鼻窦手术结果。在本研究中，在生物膜感染伤口小鼠模型中对Def - GaPP Chitogel进行了为期6天的疗效研究。研究了两种浓度的Def - GaPP Chitogel：Def - GaPP高剂量（10 mM Def + 500 µg/mL GaPP）和Def - GaPP低剂量（5 mM Def + 200 µg/mL GaPP）。高剂量Def - GaPP治疗从第2天起降低了体内细菌负荷，且未延迟伤口闭合。此外，Def - GaPP治疗减少了伤口炎症，表现为中性粒细胞浸润减少，伤口床内促炎M2巨噬细胞增多以推动伤口愈合进程。Def - GaPP Chitogel治疗在减少皮肤感染方面显示出有前景的潜力，在伤口愈合进程中观察到了积极效果。
