Wound Debridement by Copper Oxide-Mediated Dressings: Bridging the Gap Between Basic Science and Clinical Augmentation of Endogenous Autolytic Pathways

Objective: The effectiveness of available wound debridement strategies, including endogenous autolysis, enzymatic, larval, and surgical approaches, is often limited by poor wound-bed biology, cost, and invasiveness. Although copper oxide–containing dressings (COD) have demonstrated broad wound-healing activity in basic science and clinical studies, their potential to modulate debridement has not been specifically characterized. Methods: We retrospectively analyzed five extreme clinical cases involving six limbs with diverse etiologies, extensive necrosis, impaired perfusion, and frequently compromised systemic conditions. Sequential clinical imaging and detailed follow-up were used to assess wound-bed dynamics. Observations were interpreted in the context of relevant published basic science. Results: In five of six limbs, major amputation or revision to a higher level had been indicated prior to COD initiation. In all cases, application of COD was associated with rapid and extensive clearance of devitalized tissue, suggesting augmentation of endogenous autolytic mechanisms. Review of the literature supports copper-dependent pathways (CDPs), including the MMP–TIMP axis, inflammatory signaling via NF-κB, and macrophage polarization. Analysis of serial photographs demonstrated concurrent emergence of granulation tissue and vascularization, supporting synergism between angiogenesis, granulation tissue formation, and debridement, all induced by COD. Conclusions: The findings support the hypothesis that copper ions and COD may amplify autolytic tissue clearance through CDPs, with concurrent synergistic interaction between angiogenesis and debridement.