4.4 Article Proceedings Paper

Surgical implantation of a bioengineered internal anal sphincter

Journal

JOURNAL OF PEDIATRIC SURGERY
Volume 45, Issue 1, Pages 52-58

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.jpedsurg.2009.10.010

Keywords

Internal anal sphincter; Fibroblastic growth factor 2; Incontinence; Tissue engineering

Funding

  1. NCI NIH HHS [P30 CA046592, 5 P03 CA46592] Funding Source: Medline
  2. NIDDK NIH HHS [R01 DK071614-04, 5R01DK071614, R01 DK071614, R01 DK042876, 2R01DK042876] Funding Source: Medline
  3. NATIONAL CANCER INSTITUTE [P30CA046592] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK042876, R01DK071614] Funding Source: NIH RePORTER

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Purpose: 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 mu g 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. Result: 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. (C) 2010 Elsevier Inc. All rights reserved.

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