Nitric Oxide-Based Strategies for Wound Healing

Nitric oxide (NO) plays a central role in the orchestration of wound repair, acting as both a signalling mediator and antimicrobial agent. Endogenous NO promotes vasodilatation, angiogenesis and the recruitment of immune cells, while exogenous NO delivery can accelerate re-epithelialisation and suppress infection. Contemporary approaches harness NO’s dual functions by incorporating NO donors into biomaterials—such as hydrogels, nanocarriers and electrospun fibres—to achieve controlled, sustained release at the wound bed. These platforms exploit stimuli-responsive elements (for example, temperature, light or pH) to trigger NO liberation in response to local cues, thereby optimising timing and dosage. In parallel, the integration of NO with complementary therapies—such as photothermal heating or antimicrobial polymers—has yielded synergistic effects, enhancing bacterial eradication and stimulating cellular migration. Collectively, NO-based strategies offer a versatile toolbox for addressing both acute and chronic wounds, including diabetic ulcers and infected surgical sites, by promoting tissue regeneration and restoring barrier function.

Research from Nature Portfolio

Recent studies have elucidated NO’s mechanism in epithelial repair through modulation of intracellular signalling cascades. Investigations using epidermal stem cells demonstrated that NO donors activate the cGMP-PKG axis, thereby upregulating RhoA and Rac1 GTPases to reorganise the cytoskeleton and enhance cell migration. This mechanism was validated in vivo, where topical NO accelerated re-epithelialisation in partial-thickness scald models. Further work in corneal healing models revealed that controlled NO supplementation increases epithelial cell proliferation and migration via time-dependent activation of MAP kinases (p38 and ERK), leading to faster wound closure and reduced opacity after alkali injury. These findings underscore NO’s capacity to regulate both keratinocyte behaviour and inflammatory cytokine profiles, laying a mechanistic foundation for translation into topical formulations.

Nitric Oxide-Based Strategies for Wound Healing publication trend

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

Technical terms

Nitric oxide (NO): A gaseous free radical that regulates vascular tone, immune responses and cell signalling during wound repair.

S-Nitrosoglutathione (GSNO): An endogenous NO donor that releases NO upon chemical or enzymatic decomposition.

Angiogenesis: The formation of new blood vessels from pre-existing vasculature, essential for supplying nutrients to healing tissue.

Hydrogel: A water-swollen polymer network used as a scaffold for controlled therapeutic delivery.

Photothermal therapy (PTT): A treatment that employs light-absorbing agents to generate localized heat for antimicrobial or tissue-modulating effects.

cGMP: Cyclic guanosine monophosphate, a second messenger activated by NO that regulates protein kinases and ion channels.

Rho GTPase: A family of small signalling proteins (including RhoA and Rac1) that control cytoskeletal dynamics and cell migration.

References

1. Enhanced Bacterial‐Infected Wound Healing by Nitric Oxide‐Releasing Topological Supramolecular Nanocarriers with Self‐Optimized Cooperative Multi‐Point Anchoring. Advanced Science (2023).
2. NIR-activated electrospun nanodetonator dressing enhances infected diabetic wound healing with combined photothermal and nitric oxide-based gas therapy. Journal of Nanobiotechnology (2024).
3. Nitric Oxide-Releasing Thermoresponsive Pluronic F127/Alginate Hydrogel for Enhanced Antibacterial Activity and Accelerated Healing of Infected Wounds. Pharmaceutics (2020).
4. Nitric oxide promotes epidermal stem cell migration via cGMP-Rho GTPase signalling. Scientific Reports (2016).
5. Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing. Scientific Reports (2017).