Arginine-Mediated Strategies for Wound Healing Applications

Arginine is a conditionally essential amino acid that serves as a precursor to nitric oxide and polyamines, both of which play pivotal roles in multiple phases of wound repair. Strategies employing local or systemic administration of l-arginine have been shown to enhance fibroblast proliferation, modulate inflammatory responses and support collagen deposition and angiogenesis. Arginase activity, directing arginine metabolism towards ornithine and urea, influences both tissue regeneration and immune balance, underscoring the dual pathways by which arginine availability can affect healing outcomes. Novel biomaterials incorporating arginine—ranging from chitosan-based scaffolds to pH-responsive hydrogels—offer controlled delivery and functional cross-linking, optimising the microenvironmental cues for cell migration and extracellular matrix synthesis. These arginine-mediated interventions address chronic and diabetic wounds characterised by impaired nitric oxide production, excessive protease activity and structural collagen disorganisation. By integrating molecular insights with material engineering, emerging therapies aim to restore the physiological wound-healing cascade, reduce infection and accelerate tissue regeneration across diverse clinical settings.

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Arginine-Mediated Strategies for Wound Healing Applications publication trend

The graph below shows the total number of articles in arginine-mediated strategies for wound healing applications across all publications each year (not limited to Nature Index journals).

Technical terms

L-arginine: A conditionally essential amino acid that serves as a precursor for nitric oxide synthesis and polyamine production, crucial for cell proliferation, immune modulation and collagen formation.

Nitric oxide synthase (NOS): A family of enzymes that catalyse the conversion of arginine to nitric oxide, a signalling molecule important in vasodilation, immune response and wound healing.

Arginase: An enzyme that hydrolyses arginine into ornithine and urea, influencing collagen synthesis and tissue regeneration by modulating arginine availability.

Fibroblast: A connective tissue cell responsible for synthesising extracellular matrix components, including collagen and elastin, and critical for wound contraction and repair.

Keratinocyte: The predominant epidermal cell type involved in re-epithelialisation, responsible for restoring the skin barrier during wound closure.

Hydrogel: A water-swollen polymeric network used as a biomaterial scaffold or dressing, capable of delivering bioactive agents and supporting cell migration.

pH-responsive scaffold: A biomaterial engineered to alter its physical or chemical properties in response to changes in local pH, enabling controlled drug release and adaptive wound support.

References

1. L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5. Molecules (2023).
2. L-Arginine Stimulates Fibroblast Proliferation through the GPRC6A-ERK1/2 and PI3K/Akt Pathway. PLOS ONE (2014).
3. Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing. Frontiers in Molecular Biosciences (2021).
4. Chitosan/cellulose nanocrystals/graphene oxide scaffolds as a potential pH-responsive wound dressing: Tuning physico-chemical, pro-regenerative and antimicrobial properties. International Journal of Biological Macromolecules (2024).
5. Short-Term l-arginine Treatment Mitigates Early Damage of Dermal Collagen Induced by Diabetes. Bioengineering (2024).