Histological evidence for enhanced anal fistula repair using autologous fibroblasts in a dermal collagen matrix

Abstract

An anal fistula has a primary track passing from an internal anal or rectal opening to an external opening in the perianal area. Surgery aims to eradicate sepsis whilst preserving faecal continence. Fistulotomy, when all tissue caudal to the primary fistulous track is opened, provides the surest method of cure but may diminish patient continence. An alternative sphincter-preserving procedure is to instill a sealant into the track. An experimental porcine model of fistula-in-ano has been developed in the Surgical Research Department at Northwick Park Institute for Medical Research. This allows histological assessment of fistula tracks after novel, sphincter-preserving surgery and treatments have been applied. Under general anaesthetic, 24 anal fistulae were created and treated, three in each of eight adult Large White/Landrace crossbred pigs. Under the same general anaesthetic, a split skin graft was taken from which to culture fibroblasts for future treatment. All tracks were treated at 4 weeks post-track induction when the tracks were established and very similar in clinical appearance to human tracks. All tracks were prepared for treatment using an instrument designed to remove granulation tissue from the wall of the track. Five control tracks were not infilled but simply had their internal and external openings closed with a Vicryl suture. Nine tracks were treated by infill using an acellular porcine dermal collagen matrix. Ten tracks were treated using a mixture of this matrix and autologous cultured fibroblasts. Histological examination of six tracks was carried out at 2 weeks, nine tracks at 2 months and nine tracks at 3 months. Histological assessment demonstrated persistent fistula tracks in only two fistulae, both of which were control tracks. All treated tracks were closed and cured at all times of examination. When autologous fibroblasts were added to the infill material, cellular integration and vascularization were improved. Using this pre-clinical model, provided fistulous tracks were prepared using a new, in-house developed instrument; treatment with acellular collagen matrix alone healed all tracks. Adding autologous fibroblasts improved the quality of wound healing. A pilot study using this treatment in human fistula patients is in progress.