Hypertrophic Scar Formation Mechanisms and Therapeutic Strategies

Hypertrophic scars arise from aberrant wound healing, characterised by persistent inflammation, excessive extracellular matrix deposition and prolonged myofibroblast activation. Following dermal injury, a finely tuned sequence of haemostasis, inflammation, proliferation and remodelling is disrupted. Key drivers include transforming growth factor-β (TGF-β) overactivity, mechanical tension across the wound bed and dysregulated cytokine expression, which together stimulate fibroblast proliferation and differentiation into contractile myofibroblasts. These cells synthesise elevated levels of collagen types I and III, fibronectin and α-smooth muscle actin, leading to raised, erythematous and pruritic scars. Matrix metalloproteinases and their inhibitors become imbalanced, hindering normal tissue remodelling. Therapeutic approaches range from silicone sheeting and pressure garments to intralesional corticosteroids and laser resurfacing, each aiming to modulate inflammation, reduce collagen synthesis or attenuate cellular contractility. Emerging strategies target molecular mediators of fibrosis, including microRNA modulation, antibody blockade of TGF-β signalling, application of exogenous extracellular vesicles and bioengineered scaffolds. Natural products and repurposed small molecules are under investigation for their capacity to restore matrix turnover and resolve chronic inflammation. A multidisciplinary approach that integrates mechanical off-loading, pharmacological modulation and tissue engineering holds promise for preventing and ameliorating hypertrophic scarring on a global scale.

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Hypertrophic Scar Formation Mechanisms and Therapeutic Strategies publication trend

The graph below shows the total number of articles in hypertrophic scar formation mechanisms and therapeutic strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Fibroblast: A mesenchymal cell responsible for synthesis of extracellular matrix and collagen during tissue repair.

Myofibroblast: A specialised fibroblast expressing contractile proteins such as α-smooth muscle actin, central to wound contraction and fibrosis.

Extracellular matrix: A complex network of proteins and glycosaminoglycans that provides structural support and signalling cues to cells.

Transforming growth factor-β (TGF-β): A cytokine that regulates cell proliferation, differentiation and extracellular matrix production, often upregulated in fibrotic disorders.

Exosome: A nanoscale extracellular vesicle released by cells, carrying proteins, lipids and nucleic acids that mediate intercellular communication.

α-Smooth muscle actin (α-SMA): An actin isoform expressed in myofibroblasts, used as a marker of fibroblast activation and contractile function.

References

1. Extracellular vesicles from Lactobacillus druckerii inhibit hypertrophic scar fibrosis. Journal of Nanobiotechnology (2023).
2. Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization. Frontiers in Immunology (2023).
3. Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin. International Journal of Molecular Sciences (2023).
4. The molecular basis of hypertrophic scars. Burns & Trauma (2016).