Section of Pediatric Surgery, University of Michigan, Mott Children's Hospital F3970, Box 0245, Ann Arbor, MI 48109-0245, USA.
J Pediatr Surg. 2010 Jan;45(1):52-8. doi: 10.1016/j.jpedsurg.2009.10.010.
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.
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.
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.
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.
粪便失禁是一种常见的疾病,会给患者带来毁灭性的社会和心理后果。然而,目前尚无长期的理想解决方案。尽管失禁的原因是多方面的,但内肛括约肌(IAS)的完整性尤为重要。我们之前曾描述过使用源自供体 C57BL/6 IAS 的分离平滑肌组织来开发 3 维生物工程构建体。我们假设生物工程环构建体在植入受鼠的皮下组织后将保持细胞活力并促进新生血管形成。
将 IAS 环构建体通过手术植入到同基因 C57BL/6 小鼠的皮下组织中,并使用微渗透泵每天用成纤维细胞生长因子 2(0.26μg)或盐水对照进行处理。在 25 天后(范围 23-26 天)收获 IAS 构建体,并进行形态学和组织活力评估。
大体形态显示没有排斥反应。环与小鼠背部附着,没有炎症迹象。与对照组相比,成纤维细胞生长因子 2 输注导致组织学评分和肌肉活力明显改善。
3 维生物工程 IAS 环可成功植入受鼠的皮下组织。成纤维细胞生长因子 2 的添加可提高肌肉活力、血管生成和存活率。这种方法可能成为粪便失禁患者的可行选择。