Revisiting the Regenerative Role of Vitamin C in Skin Ulcer Repair—Mechanistic Insights and Therapeutic Roles

Borislav B. Stoilov; Cristopher L. Delaney; Vi Khanh Truong; Krasimir A. Vasilev

doi:10.53941/rmd.2026.100010

Abstract

Skin ulcers remain a major cause of morbidity worldwide, affecting millions and burdening healthcare systems with prolonged hospitalisation. Conventional wound therapies rarely achieve full regeneration because the biochemical imbalances that sustain inflammation, oxidative stress and poor collagen deposition remain uncorrected. Among essential nutrients, vitamin C (L-ascorbic acid) has emerged as a decisive molecular regulator of cutaneous repair. Acting as a cofactor for collagen synthesis, vitamin C governs matrix synthesis, promotes angiogenic signalling and maintains immune–redox balance within the ulcer microenvironment. Accumulating evidence demonstrate direct control of cellular metabolism and gene expression by vitamin C through modulation of prolyl hydroxylases, hypoxia-inducible factor-1α, and NF-κB pathways, thus modulating fibroblast proliferation, keratinocyte differentiation, and vascular maturation. It also suppresses pathogen-driven oxidative injury, reinforcing host defence in infected ulcers. This review consolidates biochemical and clinical data to define vitamin C as a clinical modulator of chronic wound healing rather than a supportive micronutrient. The discussion connects mechanistic findings to outcomes from topical and systemic supplementation trials, highlighting how optimised vitamin C delivery can accelerate tissue regeneration and reduce infection risk. Collectively, the evidence establishes vitamin C as a practical, low-cost adjunct capable of bridging nutritional intervention and regenerative medicine for effective ulcer management.

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