Pharmacological applications of nitric oxide-releasing biomaterials in human skin

Nitric oxide (NO) is an important endogenous molecule that plays several roles in biological systems. NO is synthesized in human skin by three isoforms of nitric oxide synthase (NOS) and, depending on the produced NO concentration, it can actuate in wound healing, dermal vasodilation, or skin defense against different pathogens, for example. Besides being endogenously produced, NO-based pharmacological formulations have been devel-oped for dermatological applications targeting diverse pathologies such as bacterial infection, wound healing, leishmaniasis, and even esthetic issues such as acne and skin aging. Recent strategies focus mainly on developing smart NO-releasing nanomaterials/biomaterials, as they enable a sustained and targeted NO release, promoting an improved therapeutic effect. This review aims to overview and discuss the main mechanisms of NO in human skin, the recent progress in the field of dermatological formulations containing NO, and their application in several skin diseases, highlighting promising advances and future perspectives in the field.