Targeting the Biofilm-Microbiota-Immune Triad: Next Generation Therapeutics for Non Healing Wounds

Chronic non healing wounds, including diabetic foot ulcers and venous leg ulcers, are sustained by a pathogenic synergy between bacterial biofilms, a dysbiotic microbiota, and a dysregulated host immune response, conceptualized as the biofilm-microbiota-immune triad. Traditional therapies that target individual components of this triad have shown limited success. This systematic review synthesizes evidence from ۲۰۱۸ to ۲۰۲۴ to evaluate next generation therapeutic strategies designed to concurrently disrupt biofilms, restore microbial homeostasis, and reprogram the local immune microenvironment. Our analysis reveals that emerging approaches, such as stimuli responsive nanocarriers for quorum sensing inhibition, engineered phage cocktails, precision probiotic formulations, and host directed immunomodulators, offer promising multi target potential. However, significant challenges in clinical translation, including combinatorial product regulation, personalized formulation, and the risk of resistance to anti-virulence agents, remain. We conclude that the future of chronic wound management lies in integrated, intelligent therapeutic systems capable of dynamically responding to the wound environment. This paradigm shifts from mono target to triad targeting therapies is essential to break the cycle of chronicity and promote healing.

کلیدواژه ها:

Chronic Wound ، Biofilm ، Dysbiosis ، Immune Dysregulation ، Multi Target Therapy ، Personalized Medicine