Charge‐Driven Bioshield Remodels Diabetic Oral Microenvironment for Accelerated Wound Healing

ABSTRACT Diabetic chronic wounds, especially in the moist and mechanically dynamic oral environment, pose a significant therapeutic challenge due to neutrophil extracellular traps (NETs)‐mediated inflammation, biofilm infections, and extracellular matrix remodeling defects. To address this challenge, we develop a protein‐based adhesive bioshield, functioning through the combined action of physical blocking and electrostatic interaction, that simultaneously acts as a bacterial barrier and NETs scavenger, thereby reactivating the focal adhesion signaling. The protein's high‐density lysine residues establish a robust adhesion network that resists the dynamic oral environment while creating a persistent antibacterial bioshield. Notably, the high net charge of adhesive bioshield enables rapid NETs neutralization by electrostatically binding cell‐free DNA (cfDNA), which reduces local NETs levels and inflammatory responses. This NETs clearance subsequently alleviates inflammation‐mediated suppression of focal adhesion signaling, which coordinately accelerates diabetic wound healing through enhanced epithelial migration, endothelial proliferation, and angiogenesis. Overall, this study presents a charge‐driven therapeutic strategy that targets NETs‐mediated inflammation, offering an alternative approach for managing diabetic wounds in dynamic and wet environments.