TY - JOUR
T1 - Gastrointestinal synthetic epithelial linings
AU - Li, Junwei
AU - Wang, Thomas
AU - Kirtane, Ameya R.
AU - Shi, Yunhua
AU - Jones, Alexis
AU - Moussa, Zaina
AU - Lopes, Aaron
AU - Collins, Joy
AU - Tamang, Siddartha M.
AU - Hess, Kaitlyn
AU - Shakur, Rameen
AU - Karandikar, Paramesh
AU - Lee, Jung Seung
AU - Huang, Hen Wei
AU - Hayward, Alison
AU - Traverso, Giovanni
N1 - Funding Information:
We are grateful to R. S. Langer for invaluable guidance and comments on this work. A.R.K. is thankful to PhRMA foundation postdoctoral fellowship. We are grateful to all members of the Langer and Traverso Laboratories, especially M. Verma, T. V. Erlach, S. Babaee, J. Coffey, J. Li, H. Mazdiyasni, R. Xiao, J. Byrne, X. Lu, and C. Steiger for discussion of mechanisms and applications of GSEL. We are also grateful to E. Caffarel-Salvador, V. Soares, and M. Jimenez for help with human tissue and bacteria samples. Funding: This work was supported in part by the Bill and Melinda Gates Foundation grants (OPP1179091), the NIH (EB000244), and funds from the Department of Mechanical Engineering, MIT.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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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U2 - 10.1126/SCITRANSLMED.ABC0441
DO - 10.1126/SCITRANSLMED.ABC0441
M3 - Article
C2 - 32848090
AN - SCOPUS:85089996060
SN - 1946-6234
VL - 12
JO - Science translational medicine
JF - Science translational medicine
IS - 558
M1 - EABC0441
ER -