Wound Healing
The wound healing cascade is a highly complex series of events that if compromised contributes to significant morbidity in postsurgical patients. Its established antimicrobial, vasodilatory, angiogenic, and collagen-stimulating properties indicate the instrumental role of NO in modifying the factors essential for proper healing. There is considerable evidence for the relationship between NO and wound healing:
• States of NO deficiency, such as diabetes, malnutrition and steroid use are associated with delayed wound healing, providing clinical evidence of its importance;
• NO end products, nitrate, and nitrite are found in wound fluids, and urinary nitrate levels remain elevated until wound closure.
In contrast to the basal production of NO by endothelial NOS (eNOS), generation of NO by iNOS in response to the inflammatory wound milieu leads to a larger, more sustained release. This allows NO to be effective in all three stages of the healing process – the inflammatory, proliferative, and remodeling phases. Macrophages, acting in the beginning of the healing cascade, are responsible for the largest production of NO and utilize NO’s oxidative properties to generate reactive oxygen species for the destruction of pathogens. However, as wound healing progresses, fibroblasts, keratinocytes, endothelial cells and melanocytes take over its production, allowing NO to act continuously and impact on re-epithelialization and collagen deposition.
NO-nanoparticles enhance wound healing in vivo.
(A) Wounds of BALB/c mice at day 7.
(B) Wound healing curve.
(C) Wound closure percentage of BALB/c mice skin lesions at day 7 relative to the initial 5 mm wound.
(D) Histological analysis of untreated, control-np, and NO-np treated BALB/c mice at day 7.
np: Nanoparticles.