Immunomodulatory role of decellularized extracellular matrix in skin wound healing

The extracellular matrix (ECM) plays a pivotal role in skin wound healing by providing structural support and biochemical signals that regulate cellular behavior. Recent studies highlight the immunomodulatory properties of decellularized ECM (dECM), particularly its influence on macrophage polarization and the overall immune response, which are critical for effective tissue repair. During wound healing, macrophages transition from a pro-inflammatory to an anti-inflammatory phenotype, a process crucial for regulating angiogenesis, fibroblast proliferation, and tissue remodeling. Numerous studies have demonstrated that incorporating dECM into skin wound healing significantly enhances therapeutic outcomes by accelerating this phenotypic shift and fostering the transition to an anti-inflammatory environment. Furthermore, the decellularization process, which removes cellular components while preserving the ECM's biochemical and physical properties, has enabled the development of advanced scaffolds, hydrogels, and bioinks for biomedical applications. Despite these promising findings, the precise mechanisms underlying ECM-driven immune modulation remain unclear, limiting its full therapeutic potential of dECM in wound healing. This review summarizes current progress in ECM processing, applications, and immunological mechanisms in wound healing, with a particular focus on ECM-macrophage interactions. Additionally, it discusses future strategies for optimizing ECM-based, immunomodulation-driven approaches to wound healing.