A Sprayable Multifunctional Film Based on EGFR‐Targeting DNA Nanoactivators for Burn Wound Healing

ABSTRACT Burn treatment remains a tough clinical hurdle, as traditional epidermal growth factor (EGF) treatments suffer from rapid proteolytic degradation and poor skin permeation. Herein, a sprayable, multifunctional film (STAR) based on EGFR‐targeting DNA nanoactivators is reported for efficient burn wound healing. The STAR platform combines tannic acid (TA), silk fibroin (SF), and tetrahedral framework nucleic acids (tFNA) modified with tetravalent EGFR‐stimulating aptamers. This design leverages the nanostructure of tFNA to realize multivalent cooperativity, inducing potent and sustained EGFR activation and downstream signaling. Crucially, the ready‐to‐use dual‐component spray formulation offers superior operational convenience compared with conventional hydrogels, ensuring uniform coverage of irregular wounds. Upon co‐spraying, the system rapidly forms a robust, adhesive film in situ, providing an immediate waterproof barrier and localized antimicrobial protection against pathogens. In vitro, STAR significantly enhances the proliferation and migration of keratinocytes and fibroblasts. In vivo, therapeutic efficacy was validated in two distinct models: a full‐thickness scald model and a skin‐grafting model. STAR film exhibited prolonged retention, effectively accelerating re‐epithelialization, promoting organized collagen deposition, and resolving inflammation. Furthermore, STAR enabled suture‐free skin grafting by ensuring stable bio‐adhesion and facilitating bioactive integration at the graft–host interface. This sprayable platform offers a promising strategy for comprehensive burn management and reconstructive surgery.