Effect of Vinblastine Timing on Skin Graft Healing in a Rat Model

Background and Objectives: Chemotherapeutic agents are known to disrupt wound healing; however, the influence of administration timing on skin graft repair remains insufficiently characterized. This study aimed to investigate the time-dependent effects of vinblastine exposure on full-thickness skin graft healing in a rat model. Materials and Methods: Twenty-four female Wistar albino rats were allocated into four groups (n = 6). The control group underwent grafting without pharmacologic intervention, whereas the experimental groups received a single intraperitoneal dose of vinblastine (2 mg/kg), followed by grafting in the first week, second week and third week after administration. Graft specimens were harvested on postoperative day 7 for histopathological evaluation performed by a blinded pathologist. Hematoxylin-eosin-stained sections were scored for inflammation, granulation tissue formation, fibroblast maturation, collagen deposition, re-epithelialization, and neovascularization. Intergroup comparisons were conducted using the Kruskal-Wallis test with Dunn-Bonferroni post hoc analysis. Results: Vinblastine exposure produced significant time-dependent differences in several healing parameters. Fibroblast maturation was markedly reduced in the second-week graft group compared with controls (p < 0.001). Re-epithelialization was significantly delayed in the second- and third-week groups (p = 0.033). Granulation tissue formation differed between groups (p = 0.014), with higher early scores observed in the first-week group. Notably, neovascularization was significantly greater in the third-week group than in the control and second-week groups (p = 0.010), suggesting partial recovery of angiogenic activity over time. No significant differences were detected in inflammation or collagen deposition. Conclusions: Vinblastine exposure appears to exert time-dependent effects on skin graft healing, with the second week representing a period of less favorable histopathological repair. Partial recovery observed with later grafting suggests that the interval between chemotherapeutic exposure and reconstructive procedures may influence graft outcomes and support improved surgical planning.