Abstract
Introduction: Biodegradable polyester scaffolds have proven useful for growing neointestinal tissue equivalents both in vitro and in vivo. These scaffolds allow cells to attach and grow in a 3-dimensional space while nutrient flow is maintained throughout the matrix. The purpose of this study was to evaluate different biopolymer constructs and to determine mucosal engraftment rates and mucosal morphology. Hypothesis: We hypothesized that different biopolymer constructs may vary in their ability to provide a good scaffolding onto which intestinal stem cell organoids may be engrafted. Study Design: Eight different microporous biodegradable polymer tubes composed of polyglycolic acid (PGA), polylactic acid, or a combination of both, using different fabrication techniques were seeded with intestinal stem cell clusters obtained from neonatal rats. Three different seeded polymer constructs were subsequently placed into the omentum of syngeneic adult recipient rats (n = 8). Neointestinal grafts were harvested 4 weeks after implantation. Polymers were microscopically evaluated for the presence of mucosal growth, morphology, scar formation and residual polymer. Results: Mucosal engraftment was observed in 7 out of 8 of the polymer constructs. A maximal surface area engraftment of 36% (range 5–36%) was seen on nonwoven, randomly entangled, small fiber PGA mesh coated with aerosolized 5% poly-L-lactic acid. Villous and crypt development, morphology and created surface area were best on PGA nonwoven mesh constructs treated with poly-L-lactic acid. Electrospun microfiber PGA had poor overall engraftment with little or no crypt or villous formation. Conclusion: Intestinal organoids can be engrafted onto biodegradable polyester scaffoldings with restitution of an intestinal mucosal layer. Variability in polymer composition, processing techniques and material properties (fiber size, luminal dimensions and pore size) affect engraftment success. Future material refinements should lead to improvements in the development of a tissue-engineered intestine.
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