Modular stimuli-responsive hydrogel sealants for early gastrointestinal leak detection and containment
Abstract
Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks. Here, we present a holistic solution in the form of a modular, intelligent suture support sealant patch capable of containing and detecting leaks early. The pH and/or enzyme-responsive triggerable sensing elements can be read out by point-of-need ultrasound imaging. We demonstrate reliable detection of the breaching of sutures, in as little as 3 hours in intestinal leak scenarios and 15 minutes in gastric leak conditions. This technology paves the way for next-generation suture support materials that seal and offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.
Additional Information
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. We acknowledge financial support from the Swiss National Science Foundation (Eccellenza grant. 181290, I.K.H.), the SwissLife Foundation (I.K.H.), the Vontobel Foundation (I.K.H.), the Claude et Giuliana Foundation (I.K.H.), the Hans Gröber Foundation (I.K.H.), the Evi-Diethelm-Winteler-Foundation (I.K.H.) and the Dornonville-DeLaCour Foundation (I.K.H.). M.G.S. is supported by the US National Institutes of Health (R01EB018975, M.G.S.) and the Jacobs Institute for Molecular Engineering in Medicine (M.G.S.). M.P.A. is supported by the Agency for Science, Technology and Research of Singapore. A.H.C.A is supported by an ETH Pioneer Fellowship. We thank Apolline Anthis for her contributions towards the development of the layer-by-layer incorporation of sensing and therapeutic elements in model patches and Anna-Katharina Zehnder for her contributions towards evaluating burst pressure under digestive conditions. We thank Michel Calame for access to the Raman microscope, the Empa Biointerfaces lab for access to the bacteria lab and the Empa Electron Microscopy Center for access to the SEM. The schematics and pictograms in the figures were created using BioRender.com. Author contributions. A.H.C.A. contributed to study design, developed, and identified all the polymer and functional element formulations, performed experiments, analysed data and drafted the manuscript. M.P.A. produced GVs, provided guidance in working with GVs. A.L.N. performed cytocompatibility analysis. E.T. performed electron microscopy. J.R. performed animal surgeries. T.R. provided crucial input for ultrasound imaging. F.H.L Starsich synthesized the zinc oxide nanoparticles. B.W. supervised and performed the tensile tests together with A.H.C.A. V.L. supervised the animal work. A.A.S. provided clinical input and contributed to study design. M.S. supervised the GV production and provided guidance in working with GVs. I.K.H. conceived, designed and supervised the study, performed the Raman spectromicroscopy and co-wrote the manuscript. All authors contributed to discussions and edited the manuscript. Data availability. All the data supporting the findings of this study are available within the main text of this article and its Supplementary Information, or from the corresponding authors upon request. Source data are provided with this paper. Competing interests. A.H.C.A. and I.K.H. declare that patent applications have been filed covering all parts of the adhesion and sensing technology reported in this publication. The patents have been filed by ETH Zurich and Empa (Alexandre H.C. Anthis, Martin T. Matter and Inge K. Herrmann, PCT/EP2022/051137, patent field and Alexandre H.C. Anthis, Benjamin Suter and Inge K. Herrmann, PCT/EP2022/051141, patent filed). All other authors report no conflict of interest.Attached Files
Published - 41467_2022_Article_34272.pdf
Supplemental Material - 41467_2022_34272_MOESM1_ESM.pdf
Supplemental Material - 41467_2022_34272_MOESM4_ESM.xlsx
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Additional details
- PMCID
- PMC9701692
- Eprint ID
- 118334
- Resolver ID
- CaltechAUTHORS:20221213-185576500.5
- Swiss National Science Foundation (SNSF)
- 181290
- SwissLife Foundation
- Vontobel Foundation
- Claude et Giuliana Foundation
- Hans Gröber Foundation
- Evi-Diethelm-Winteler-Foundation
- Dornonville-DeLaCour Foundation
- NIH
- R01EB018975
- Jacobs Institute for Molecular Engineering for Medicine
- Agency for Science, Technology and Research (A*STAR)
- ETH Zurich
- Created
-
2023-01-18Created from EPrint's datestamp field
- Updated
-
2023-10-24Created from EPrint's last_modified field
- Caltech groups
- Jacobs Institute for Molecular Engineering for Medicine