Molecular Mechanisms in Skin Wound Healing

The repair of skin following injury is a highly orchestrated process that involves sequential but overlapping phases of haemostasis, inflammation, proliferation and remodelling. At the molecular level, the initial haemostatic response is mediated by clotting factors and platelet-derived growth factors, providing a provisional matrix rich in fibrin. Inflammation recruits neutrophils and macrophages that clear debris and secrete cytokines such as tumour necrosis factor and interleukins, setting the stage for the proliferative phase. During proliferation, keratinocytes migrate to re-epithelialise the wound, fibroblasts synthesise extracellular matrix components including collagen and fibronectin, and endothelial cells form new capillaries by angiogenesis. Growth factors such as transforming growth factor β, vascular endothelial growth factor and basic fibroblast growth factor drive these events through key signalling cascades, notably the mitogen-activated protein kinase and PI3K/Akt pathways. In the final remodelling phase, matrix metalloproteinases and tissue inhibitors of metalloproteinases balance matrix deposition and degradation to restore tensile strength. Dysregulation at any molecular checkpoint can lead to chronic non-healing ulcers or excessive scarring, underscoring the global need for targeted therapies that modulate specific wound-healing pathways.

Research from Nature Portfolio

Recent studies have revealed that paradoxical activation of the MAPK pathway can be harnessed therapeutically. Topical application of a BRAF inhibitor was found to induce extracellular signal-regulated kinase phosphorylation, accelerating keratinocyte proliferation and migration in murine models. Co-administration of a MEK inhibitor reversed this effect, confirming the specificity of MAPK activation. Importantly, wound closure was faster without an associated rise in skin-cancer incidence, highlighting the potential for repurposing targeted kinase inhibitors to expedite cutaneous repair.

Molecular Mechanisms in Skin Wound Healing publication trend

The graph below shows the total number of articles in molecular mechanisms in skin wound healing across all publications each year (not limited to Nature Index journals).

Technical terms

Keratinocyte: A skin cell type responsible for re-epithelialisation of wounds through migration and proliferation.

Fibroblast: A connective-tissue cell that synthesises extracellular matrix proteins such as collagen during tissue repair.

Extracellular matrix (ECM): A network of proteins and glycoproteins that provides structural support and biochemical cues for cells.

Angiogenesis: The formation of new blood vessels from pre-existing vasculature, essential for nutrient delivery in healing tissue.

Reactive oxygen species (ROS): Chemically reactive molecules that modulate cell signalling and defence but require tight regulation to prevent damage.

Mitogen-activated protein kinase (MAPK) pathway: A signalling cascade that transmits extracellular signals to control cell proliferation, migration and gene expression.

Nanoparticle: A particle with dimensions under 100 nm, used to deliver therapeutic agents or modulate biological responses at the molecular level.

Hydrogel: A water-swollen polymeric network that can mimic the ECM, serve as a delivery scaffold and regulate wound-healing microenvironments.

References

1. Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization. Journal of Nanobiotechnology (2023).
2. Self‐Assembling Peptide‐Based Hydrogels for Wound Tissue Repair. Advanced Science (2022).
3. Mesoporous polydopamine nanoparticles carrying peptide RL-QN15 show potential for skin wound therapy. Journal of Nanobiotechnology (2021).
4. Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors. Nature Communications (2016).