Magnetic Living Hydrogels for Intestinal Localization, Retention, and Diagnosis

Xinyue Liu; Yueying Yang; Maria Eugenia Inda; Shaoting Lin; Jingjing Wu; Yoonho Kim; Xiaoyu Chen; Dacheng Ma; Timothy K. Lu; Xuanhe Zhao

doi:10.1002/adfm.202010918

Magnetic Living Hydrogels for Intestinal Localization, Retention, and Diagnosis

Xinyue Liu (Co-first Author)
, Yueying Yang (Co-first Author)
, Maria Eugenia Inda (Co-first Author)
, Shaoting Lin
, Jingjing Wu
, Yoonho Kim
, Xiaoyu Chen
, Dacheng Ma
, Timothy K. Lu^*
, Xuanhe Zhao^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

169 Citations (Scopus)

Abstract

Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease-associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier. © 2021 Wiley-VCH GmbH.

Original language	English
Article number	2010918
Number of pages	13
Journal	Advanced Functional Materials
Volume	31
Issue number	27
Online published	23 Apr 2021
DOIs	https://doi.org/10.1002/adfm.202010918
Publication status	Published - 2 Jul 2021
Externally published	Yes

Funding

X.L., Y.Y., and M.E.I. contributed equally to this work. The authors thank Tian Luo, Cheng Chang, Karen Pepper, Liu Wang, Sufeng Zhang, and Huanhuan Tian for helpful discussion; Mark Mimee for providing biosensor bacteria; and Milton Cornwall-Brady, Virginia Spanoudaki, David Bono, and Bogdan Fedeles for their training and assistance in operating the analytical instrumentations. This work is supported by MIT, the US National Science Foundation (NSF; EFMA-1935291, CCF-1521925 and DMR-1419807), Defense Threat Reduction Agency (DTRA; E2045481 via George Mason University, HDTRA1-15-1-0050, and HDTRA1-14-1-0007), Leona M. and Harry B. Helmsley Charitable Trust (3239), National Institutes of Health (NIH; 229825 via Massachusetts General Hospital, 4-R33-AI121669-04, 1R01HL153857-01), U.S. Army Medical Research and Material Command (W81XWH-16-1-0565, W81XWH-17-1-0159, and W81XWH-18-1-0513), Space and Naval Warfare Systems Center (N66001-13-C-4025), Defense Advanced Research Projects Agency (DARPA; 152304.5106735.0006 and HR0011-15-C-0084), Army Research Office (W911NF-17-2-0077, W911NF-13-D-0001 T.O. 8), Human Frontier Science Program (LT000595/2017-L), Singapore-MIT Alliance for Research and Technology (S.M.A.R.T.), and Pew Charitable Trusts (to M.E. Inda; 00030623).

Research Keywords

blood sensors
ingestible materials
intestinal retention
magnetic hydrogels
synthetic biology

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10.1002/adfm.202010918

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title = "Magnetic Living Hydrogels for Intestinal Localization, Retention, and Diagnosis",

abstract = "Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease-associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier. {\textcopyright} 2021 Wiley-VCH GmbH.",

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Magnetic Living Hydrogels for Intestinal Localization, Retention, and Diagnosis. / Liu, Xinyue (Co-first Author); Yang, Yueying (Co-first Author); Inda, Maria Eugenia (Co-first Author) et al.
In: Advanced Functional Materials, Vol. 31, No. 27, 2010918, 02.07.2021.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

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AU - Liu, Xinyue

AU - Yang, Yueying

AU - Inda, Maria Eugenia

AU - Lin, Shaoting

AU - Wu, Jingjing

AU - Kim, Yoonho

AU - Chen, Xiaoyu

AU - Ma, Dacheng

AU - Lu, Timothy K.

AU - Zhao, Xuanhe

PY - 2021/7/2

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N2 - Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease-associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier. © 2021 Wiley-VCH GmbH.

AB - Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease-associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier. © 2021 Wiley-VCH GmbH.

KW - blood sensors

KW - ingestible materials

KW - intestinal retention

KW - magnetic hydrogels

KW - synthetic biology

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U2 - 10.1002/adfm.202010918

DO - 10.1002/adfm.202010918

M3 - RGC 21 - Publication in refereed journal

SN - 1616-301X

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JO - Advanced Functional Materials

JF - Advanced Functional Materials

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M1 - 2010918

ER -

Magnetic Living Hydrogels for Intestinal Localization, Retention, and Diagnosis

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