Myogenic stem cell-laden hydrogel scaffold in wound healing of the disrupted external anal sphincter.

Abstract

To evaluate the effect of myogenic stem cell-laden hydrogel scaffold on contractile function and histomorphology of the external anal sphincter (EAS) after transection without repair. Eighty female rats underwent anal sphincter transection without repair. After 2 weeks, animals were injected at the transection site with: nothing (non-repaired control, NRC group); a polyethylene glycol-based hydrogel matrix scaffold combined with phosphate-buffered saline (PBS/hydrogel group); a hydrogel matrix scaffold combined with myogenic stem cells (stem cell/hydrogel group): or type I collagen (collagen) group. 4 (n = 40) or 12 (n = 40) weeks later, the anal sphincter complexes were dissected out and analyzed for contractile function, disruption, and striated muscle volume. Time-matched unoperated controls (UOC) were utilized for each of the two time points (n = 20). After 4 weeks, maximal electrical field-stimulated (EFS) contractions were significantly decreased in all four non-repaired treatment groups compared with UOC. However, EFS-stimulated contractions, tetanic force generation, and twitch tension were improved in non-repaired EAS injected with stem cell/hydrogel group relative to the NRC, PBS/hydrogel, or collagen groups. NRC and sphincters injected with PBS/hydrogel deteriorated further by 12 weeks, while those receiving stem cell/hydrogel maintained improved contractile function at varying frequencies and voltages. Striated muscle volume increased from 4 to 12 weeks for PBS/hydrogel and stem cell/hydrogel animals. At 12 weeks, stem cell/hydrogel animals had greater sphincter striated muscle volumes compared with all other treatment groups. In this animal model, sustained improvement of contractile responses in non-repaired EAS treated with biogel scaffold and myogenic stem cells suggests that a biologically compatible matrix may facilitate stem cell survival, differentiation, or function leading to recovery of contractile function even after persistent disruption.