Translational Extracellular Matrix Spray-Coating Approach for Large-Scale Bioactive Surface Functionalization and Tissue Repair.

While various extracellular matrix (ECM)-based delivery platforms such as cell sheets, nanoparticles, and dressings have demonstrated potential for tissue repair, their clinical translation remains limited by poor scalability, structural fragility, and substrate-specific constraints. This study introduces a translational spray-coating strategy capable of conformationally activating ECM proteins, specifically fibronectin (FN) and collagen (COL), via mechanical unfolding during deposition. Using a commercially available airbrush, micrometer-scale droplets are uniformly deposited onto diverse biomedical substrates, including polydioxanone sutures and oxidized regenerated cellulose/collagen dressings, without structural damage. Notably, FN undergoes conformational changes that enhance cell adhesion, while multi-ECM sprays promote fibrillogenesis, directional matrix organization, and increase fibroblast migration and proliferation. In a full-thickness murine wound model, sequential ECM spraying results in a 88.2% wound closure rate and 66.6% COL density, outperforming both drop-treated and commercial control groups. These findings position ECM spray-coating as a scalable, bioactive platform for advanced wound therapy and surface functionalization in regenerative medicine.