PRS AAPS Oral Proofs 2016
Zachary P. French, BSE, Shiuhyang Kuo, DDS, Jana D. Moon, BS, Eve Bingham, MS, Zhifa Wang, MD, Elizabeth A. Mays, MSE, Hyungjin (Myra) Kim, PhD, Paul S. Cederna, MD, Cynthia L. Marcelo, PhD, Stephen E. Feinberg, DDS, PhD, Melanie G. Urbanchek, PhD
From the University of Michigan, Ann Arbor, Mich.
PURPOSE: Our long-term goal is to return dependable, self-controlled, anal function with a neoanal sphincter. This study in the rat combines a prelaminated, tissue-engineered human muco-keratinocyte lining with a rat latissimus dorsi muscle flap that is constructed into a neosphincter. The purpose is to determine the impacts an acellular dermal matrix (ADM) and ADM with cells have on the contraction (squeezing) of neosphincters.
METHODS: Human muco-keratinocytes were prelaminated on an ADM in culture before rat implantation. Then, neosphincters were constructed on the shoulders of athymic rats using a latissimus dorsi muscle flap with an intact neurovascular pedicle. Three experimental groups were as follows: neosphincter (muscle only, n = 5), neosphincter with ADM (n = 4), and neosphincter with prelaminated mucosa (n = 7). Neosphincters were evaluated for contractile force across the lumen diameter 14 days after implantation.
RESULTS: All neosphincters were well vascularized, contractile, and with an open lumen. Muco-keratinocytes continued to divide with the mucosal layer increasing in thickness. Muscle fibers remained healthy, whereas ADM became vascularized. Sphincter maximal isometric forces were similar across groups.
CONCLUSIONS: By confirming the functioning and health of neosphincters constructed with prelaminated human muco-keratinocytes, this technology is moved closer to human implementation.