Protease-driven approaches for wound eschar debridement and biofilm disruption: current advances, future prospects, and limitations

Chronic wounds frequently develop eschar, a dense layer of necrotic tissue that impedes healing and fosters bacterial biofilm formation. Biofilms, protected within an extracellular polymeric substance, show high resistance to antimicrobial agents, making wound management challenging. Conventional surgical debridement, though effective, is invasive, painful, and damages healthy tissue. Enzymatic debridement using proteolytic enzymes provides a less invasive, selective alternative. This review summarizes advances in protease-based therapies from plant, bacterial, and recombinant sources, focusing on their dual role in degrading eschar proteins and disrupting biofilm architecture. By elucidating the mechanisms through which proteases hydrolyze structural proteins and dismantle biofilms, we highlight their potential as minimally invasive interventions that enhance healing, reduce infection, and improve patient outcomes.