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.