Research ArticleBIOMATERIALS

Gastrointestinal synthetic epithelial linings

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Science Translational Medicine  26 Aug 2020:
Vol. 12, Issue 558, eabc0441
DOI: 10.1126/scitranslmed.abc0441

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A salubrious solution for the small intestine

Orally delivered drugs are primarily absorbed in the small intestine, which is also the major site of nutrient absorption. Li and colleagues developed a versatile polydopamine-based solution that can coat and polymerize in situ in the small intestine. The synthetic coating adhered to pig and human tissue ex vivo, remaining stable for up to 24 hours. When administered to pigs endoscopically, polydopamine solution with suspended β-galactosidase increased digestive enzyme activity, whereas solution with embedded polydopamine nano–cross-linkers created a coating with transient barrier function that prevented glucose absorption. Encapsulating the anthelmintic drug praziquantel in polydopamine solution enhanced intestinal retention and adsorption in pigs, demonstrating the potential utility of this biomaterial for drug delivery.

Abstract

Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the small intestine, given its role in drug and nutrient absorption and identified catalase as an essential enzyme with the potential to catalyze polymerization and growth of synthetic biomaterial layers. We demonstrated that the polymerization of dopamine by catalase yields strong tissue adhesion. We characterized the mechanism and specificity of the polymerization in segments of the gastrointestinal tracts of pigs and humans ex vivo. Moreover, we demonstrated proof of concept for application of these gastrointestinal synthetic epithelial linings for drug delivery, enzymatic immobilization for digestive supplementation, and nutritional modulation through transient barrier formation in pigs. This catalase-based approach to in situ biomaterial generation may have broad indications for gastrointestinal applications.

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