Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study

Fecal incontinence (FI) is the involuntary passage of fecal material. Current treatments have limited successful outcomes. The objective of this study was to develop a large animal model of passive FI and to demonstrate sustained restoration of fecal continence using anorectal manometry in this model after implantation of engineered autologous internal anal sphincter (IAS) biosphincters. Twenty female rabbits were used in this study. The animals were divided into three groups: (a) Non-treated group: Rabbits underwent IAS injury by hemi-sphincterectomy without treatment. (b) Treated group: Rabbits underwent IAS injury by hemi-sphincterectomy followed by implantation of autologous biosphincters. (c) Sham group: Rabbits underwent IAS injury by hemi-sphincterectomy followed by re-accessing the surgical site followed by immediate closure without implantation of biosphincters. Anorectal manometry was used to measure resting anal pressure and recto-anal inhibitory reflex (RAIR) at baseline, 1 month post-sphincterectomy, up to 3 months after implantation and post-sham. Following sphincterectomy, all rabbits had decreased basal tone and loss of RAIR, indicative of FI. Anal hygiene was also lost in the rabbits. Decreases in basal tone and RAIR were sustained more than 3 months in the non-treated group. Autologous biosphincters were successfully implanted into eight donor rabbits in the treated group. Basal tone and RAIR were restored at 3 months following biosphincter implantation and were significantly higher compared with rabbits in the non-treated and sham groups. Histologically, smooth muscle reconstruction and continuity was restored in the treated group compared with the non-treated group. Results in this study provided promising outcomes for treatment of FI. Results demonstrated the feasibility of developing and validating a large animal model of passive FI. This study also showed the efficacy of the engineered biosphincters to restore fecal continence as demonstrated by manometry.