Topical hyaluronic acid serum, oral vitamin C, and their combined regimen modulate collagen-related repair indices in a sutured primary-intention rat incisional wound model.

Healing a skin wound is a complex biological process that proceeds through three stages: inflammation, proliferation, and remodeling. Hyaluronic acid (HA) and vitamin C may help tissues heal in different but complementary ways. This study aimed to examine and compare the effects of HA and vitamin C, alone and in combination, on collagen-related histological and immunohistochemical repair indices at day 22 in a rat sutured incisional wound model. Twenty adult male albino rats were divided into four equal groups (n = 5/group) at random: the control, vitamin C-treated, HA-treated, and combined HA + vitamin C-treated groups. Each animal received a standardized sutured full-thickness cutaneous incision to model primary-intention wound healing. Treatments were administered daily for 21 days using different administration routes: topical HA, oral vitamin C, or their combined regimen; wound tissue was collected on day 22 to evaluate late histological and immunohistochemical repair outcomes after completion of the treatment period. Hematoxylin and eosin, Masson's trichrome, and collagen type I immunohistochemistry were used to evaluate collagen-related histological and immunohistochemical repair features. Collagen type I expression, collagen deposition, and fibroblast count were quantified by morphometry. The H&E-based fibroblast-like cell count showed an exploratory between-group difference in the primary ANOVA analysis (p = 0.039), with the HA + vitamin C group having the highest mean; however, pairwise significance was limited to the comparison with the water-treated group, and the non-parametric sensitivity analysis was more conservative. Collagen deposition was higher in the combined-treatment group than in the water, HA-alone, and vitamin C-alone groups, and the difference was significant (p < 0.001). Additionally, collagen type I expression varied significantly (p = 0.003), with the HA + vitamin C group having the highest mean area percentage and significant pairwise differences compared to the water and vitamin C groups. At day 22, the combined HA + vitamin C regimen showed the highest collagen deposition and collagen type I immunopositive area among the tested groups, whereas the fibroblast-like cell-count finding was less robust. These preliminary findings are limited to late histological and immunohistochemical outcomes in a small sutured-incision model and do not establish functional benefit or an HA-vitamin C interaction.