Surgical implantation of a bioengineered internal anal sphincter.
OBJECTIVE
Fecal incontinence is a common disorder that can have devastating social and psychologic consequences. However, there are no long-term ideal solutions for such patients. Although loss of continence is multifactorial, the integrity of the internal anal sphincter (IAS) has particular significance. We previously described the development of 3-dimensional bioengineered constructs using isolated smooth muscle tissue from donor C57BL/6 IAS. We hypothesized that the bioengineered ring constructs would retain cellular viability and promote neovascularization upon implantation into a recipient mouse.


METHODS
Internal anal sphincter ring constructs were surgically implanted into the subcutaneous tissue of syngeneic C57BL/6 mice and treated with either fibroblastic growth factor 2 (0.26 microg daily) or saline controls using a microosmotic pump. Internal anal sphincter constructs were harvested after 25 days (range, 23-26 days) and assessed morphologically and for tissue viability.


RESULTS
Gross morphology showed that there was no rejection. Rings showed muscle attachment to the back of the mouse with no sign of inflammation. Fibroblastic growth factor 2 infusion resulted in a significantly improved histologic score and muscle viability compared with the control group.


CONCLUSIONS
Three-dimensional bioengineered IAS rings can be successfully implanted into the subcutaneous tissue of recipient mice. The addition of fibroblastic growth factor 2 led to improved muscle viability, vascularity, and survival. This approach may become a feasible option for patients with fecal incontinence.
Hashish
Mohamed
M
Section of Pediatric Surgery, University of Michigan, Mott Children's Hospital F3970, Box 0245, Ann Arbor, MI 48109-0245, USA.
Raghavan
Shreya
S
Somara
Sita
S
Gilmont
Robert R
RR
Miyasaka
Eiichi
E
Bitar
Khalil N
KN
Teitelbaum
Daniel H
DH
D001003:Anal Canal / Q000502:physiology / Q000601:surgery*; D000818:Animals; D001698:Biomedical Engineering; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005242:Fecal Incontinence / Q000601:surgery; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use; D006801:Humans; D008365:Manometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000166:cytology / Q000601:surgery; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D011474:Prosthesis Design; D019919:Prosthesis Implantation / Q000379:methods*; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*
D016222:Fibroblast Growth Factor 2