Molecular Mechanisms of Wound Healing in Model Organisms

Wound healing is a conserved, multi-phase process that restores tissue integrity following injury. In the immediate aftermath of tissue damage, haemostasis and clot formation create a provisional matrix. This is followed by an inflammatory phase in which innate immune cells—principally neutrophils and macrophages—enter the wound milieu, clearing debris and releasing cytokines and growth factors. Reactive oxygen species (ROS) generated at the wound edge serve both as antimicrobial agents and as secondary messengers that shape downstream repair programmes. During the proliferative phase, keratinocytes migrate to reseal the epithelial barrier while endothelial cells sprout new capillaries (angiogenesis) to revascularise the tissue. Concurrently, fibroblasts synthesise and remodel extracellular matrix (ECM) components, notably collagen, to form granulation tissue. In resolving wounds, anti-inflammatory macrophages and regulatory signals promote tissue remodelling and maturation, culminating in either scar formation or, in highly regenerative species, scar-free repair. Model organisms such as zebrafish, fruit fly and murine systems have revealed core molecular circuits—ranging from actin-nucleating factors that drive cell migration to transcriptional programmes activated by hypoxia-inducible factors—that underlie these universal stages. Comparative studies highlight species-specific adaptions to achieve rapid regeneration or fibrosis, offering targets for therapeutic modulation of human wound repair.

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Molecular Mechanisms of Wound Healing in Model Organisms publication trend

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Technical terms

Reactive oxygen species (ROS): chemically reactive oxygen derivatives that mediate microbial defence and intracellular signalling in wounds.

Keratinocyte: an epithelial cell type that migrates to re-epithelialise the wound surface.

Arp2/3 complex: a protein assembly that nucleates branched actin networks to power cell movement.

Macrophage: an immune cell that orchestrates inflammation, phagocytosis and tissue remodelling.

Angiogenesis: the sprouting of new blood vessels from existing vasculature to perfuse regenerating tissue.

Extracellular matrix (ECM): a structural network of proteins and glycoproteins that supports cell adhesion, migration and differentiation.

Hypoxia-inducible factor 1α (HIF1α): a transcription factor activated under low oxygen that regulates genes for metabolic adaptation and angiogenesis.

References

1. Damage-induced basal epithelial cell migration modulates the spatial organization of redox signaling and sensory neuron regeneration. eLife (2024).
2. How to initiate tissue regeneration by generating mutually exclusive cell states. PLOS Biology (2023).
3. Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metabolism (2021).