Functional and Histological Evidence for the Targeted Therapy Using Biocompatible Polycaprolactone Beads and Autologous Myoblasts in a Dog Model of Fecal Incontinence

BACKGROUND: Injection of bulking agents into the anal canal is limited by several factors, including biological resorption, particle migration, and ongoing degradation of the injected bulking agent. OBJECTIVE: We investigated whether an injection of polycaprolactone beads containing autologous myoblasts could improve sphincter function in a dog model of fecal incontinence. DESIGN: The control sham surgery group underwent skin incision around the anal sphincter (n = 5). Fecal incontinence was induced by resecting 25% of the posterior internal/external anal sphincter in another 10 dogs. After 1 month of sphincter injury, dogs were then treated with (n = 5) or without (n = 5) polycaprolactone beads containing PKH-26-labeled autologous myoblasts. SETTING: This study was conducted at the department of surgery in collaboration with the department of advanced materials. OUTCOME MEASURES: Three months after injection treatment, the resting and contractile pressure differences of the anal sphincter were compared, and histopathological studies were performed. RESULTS: The anal pressures in untreated dogs were significantly lower than those in the sham surgery group (p < 0.05). The resting and contractile pressure differences were higher in treated dogs than in untreated dogs (resting pressure difference: 0.7 +/- 0.5 vs -0.6 +/- 0.8 mmHg; coefficient of the difference in recovery rate, 0.38; 95% CI, 0.15-0.61, p = 0.001; contractile pressure difference: 1.1 +/- 4.2 vs -3.9 +/- 2.6 mmHg; coefficient, 1.63; 95% CI, 0.55-2.71, p = 0.003). Immunofluorescent staining confirmed that the myoblasts had differentiated and synthesized myosin heavy chain, as observed in vitro. LIMITATIONS: This study was limited by the lack of comparison of injecting beads containing autologous myoblasts with injecting myoblasts alone. CONCLUSION: This study shows that an injection of polycaprolactone beads containing autologous myoblasts may improve anal sphincter function in an animal model of fecal incontinence.