Therapeutic potential of epidermal growth factor for perianal fistulas: an experimental rat model

This study aimed to evaluate the effects of Epidermal Growth Factor (EGF) on wound healing, inflammation, and apoptosis markers in a rat perianal fistula model and to compare these effects with conventional seton placement, Tarantula cubensis venom (Theranekron® D6), or a combination (S + T). We hypothesized that EGF could enhance epithelial and granulation tissue repair while limiting local inflammatory damage. A total of 28 male Wistar rats were randomly allocated to four groups (n = 7 each). Perianal fistulas were experimentally induced, and interventions were administered as follows: Group S (loose seton only), Group T (Tarantula venom subcutaneously, weekly), Group S + T (seton plus tarantula venom), and EGF (two doses of 15 µg EGF near the fistula tract). After a 30-day follow-up, the animals were euthanized and the perianal regions were excised. Re-epithelialization, granulation tissue, inflammatory cell infiltration, and Caspase-3 immunostaining were analyzed. Data were statistically assessed using Kruskal-Wallis and post-hoc tests (p < 0.05). The EGF group showed markedly higher re-epithelialization scores than did the seton alone (S) and tarantula venom (T) groups. Granulation tissue was predominantly absent or immature in EGF compared to the mature or overly fibrotic profiles in the S and T groups. Inflammatory cell infiltration was significantly lower in EGF, whereas T demonstrated increased inflammation and highest Caspase-3 activity (74%). EGF maintained a minimal apoptotic response (~ 8.6% Caspase-3). EGF administration promoted favorable wound healing parameters, including enhanced re-epithelialization, reduced inflammatory infiltration, and minimal apoptotic injury in a rat perianal fistula model. Tarantula venom contributed to greater tissue damage, and seton placement alone achieved moderate outcomes. These findings suggest that EGF shows promise as an adjunctive treatment for perianal fistulas. However, its translational potential requires further investigation in clinical practice.