Inflammation and wound healing: a comprehensive overview of mechanisms, therapeutic strategies, and translational perspectives

Wound healing is the dynamic biological process by which an organism restores homeostasis following injury and is characterized by a series of stages resulting in hemostasis, inflammatory response, proliferation, and tissue remodeling. As a consequence, the inflammatory response represents a key early step in this process and plays a central role in clearing necrotic debris and pathogens, as well as inducing reparative pathways. Mild to moderate inflammation induces angiogenesis, fibroblast activation, and extracellular matrix (ECM) remodeling, whereas chronic or excessive inflammation causes tissue damage, fibrosis, and chronic non-healing wounds. The current review systematically illustrates the contribution and dynamics of the inflammatory response underlying wound healing. These processes consist of immune cell polarization, regulation of cytokines and chemokines, and signaling network dynamics, hence emphasis is laid on the canonical mechanism for maintaining steady-state tissue restoration, namely, immune homeostasis. Moreover, this review examines the dynamic cross-talk of growth factors, ECM components, and angiogenesis in different healing phases. An overview of novel interventions is also included such as negative pressure wound therapy (NPWT), hyperbaric oxygen, exosome-based approaches, biomaterial-based approaches, nanohydrogel systems, and microneedle-facilitated delivery, with insights into mechanisms and translational progress. Critical clinical translation barriers, including wound heterogeneity, host-microbe cross-talk, and limitations of model extrapolation as well as the potential application of multi-omics integration and an interdisciplinary approach towards precision wound healing, are discussed. Overall, regulation of inflammation is the foundation for the whole wound healing cascade, and immune homeostasis is a key prerequisite for injury repair. Tailored therapeutic strategies might thus greatly enhance healing outcomes and clinical efficacy.