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.

Biomedical Center Faculty of Medicine in Pilsen Charles University Prague Czech Republic

Department of Gynaecology Cantonal Hospital St Gallen Rorschacherstrasse 95 CH 9007 St Gallen Switzerland

Department of Surgery Faculty of Medicine in Pilsen Charles University Prague Czech Republic

Department of Visceral Surgery and Transplantation University Hospital Zurich CH 8091 Zurich Switzerland

Division of Chemistry and Chemical Engineering California Institute of Technology Pasadena CA 91125 USA

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Centre of Preclinical Research Milan 20122 Italy

Howard Hughes Medical Institute Pasadena CA 91125 USA

Laboratory for Mechanical Systems Engineering Department of Engineering Sciences Empa Swiss Laboratories for Materials Science and Technology Ueberlandstrasse 129 CH 8600 Dübendorf Switzerland

Laboratory for Particles Biology Interactions Department Materials Meet Life Swiss Federal Laboratories for Materials Science and Technology Lerchenfeldstrasse 5 CH 9014 St Gallen Switzerland

Nanoparticle Systems Engineering Laboratory Department of Mechanical and Process Engineering ETH Zurich Sonneggstrasse 3 CH 8092 Zurich Switzerland

Swiss HPB and Transplant Center Zurich Rämistrasse 100 CH 8091 Zurich Switzerland

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McGiffin, T. et al. Surgical management and long-term functional outcomes after anastomotic leak in patients undergoing minimally invasive restorative rectal resection and without a diverting ileostomy. ANZ J. Surg. n/a,. PubMed

Ryu JH, et al. Multipurpose intraperitoneal adhesive patches. Adv. Funct. Mater. 2019;29:1900495. doi: 10.1002/adfm.201900495. DOI

Sciuto A, et al. Predictive factors for anastomotic leakage after laparoscopic colorectal surgery. World J. Gastroenterol. 2018;24:2247–2260. doi: 10.3748/wjg.v24.i21.2247. PubMed DOI PMC

Nordentoft T, Pommergaard H-C, Rosenberg J, Achiam MP. Fibrin glue does not improve healing of gastrointestinal anastomoses: a systematic review. Eur. Surg. Res. 2015;54:1–13. doi: 10.1159/000366418. PubMed DOI

Choudhuri AH, Uppal R. Predictors of septic shock following anastomotic leak after major gastrointestinal surgery: An audit from a tertiary care institute. Indian J. Crit. Care Med. Peer-Rev. Publ. Indian Soc. Crit. Care Med. 2013;17:298–303. PubMed PMC

Hammond J, Lim S, Wan Y, Gao X, Patkar A. The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and economic outcomes. J. Gastrointest. Surg. 2014;18:1176–1185. doi: 10.1007/s11605-014-2506-4. PubMed DOI PMC

Adamina M, et al. Monitoring c-reactive protein after laparoscopic colorectal surgery excludes infectious complications and allows for safe and early discharge. Surg. Endosc. 2014;28:2939–2948. doi: 10.1007/s00464-014-3556-0. PubMed DOI

Thomas MS, Margolin DA. Management of colorectal anastomotic leak. Clin. Colon Rectal Surg. 2016;29:138–144. doi: 10.1055/s-0036-1580630. PubMed DOI PMC

Ferko A, Rejholoc J, Škrovina M, Tachecí I, Sirák I. Colorectal anastomosis dehiscence: a call for more detailed morphological classification. Videosurgery Miniinvasive Tech. 2020;16:98–109. doi: 10.5114/wiitm.2020.97367. PubMed DOI PMC

Foppa C, Ng SC, Montorsi M, Spinelli A. Anastomotic leak in colorectal cancer patients: New insights and perspectives. Eur. J. Surg. Oncol. 2020;46:943–954. doi: 10.1016/j.ejso.2020.02.027. PubMed DOI

Zhang H-Y, et al. To drain or not to drain in colorectal anastomosis: a meta-analysis. Int. J. Colorectal Dis. 2016;31:951–960. doi: 10.1007/s00384-016-2509-6. PubMed DOI PMC

Gavriilidis P, Azoulay D, Taflampas P. Loop transverse colostomy versus loop ileostomy for defunctioning of colorectal anastomosis: a systematic review, updated conventional meta-analysis, and cumulative meta-analysis. Surg. Today. 2019;49:108–117. doi: 10.1007/s00595-018-1708-x. PubMed DOI

Annabi N, Yue K, Tamayol A, Khademhosseini A. Elastic sealants for surgical applications. Eur. J. Pharm. Biopharm. 2015;95:27–39. doi: 10.1016/j.ejpb.2015.05.022. PubMed DOI PMC

Histopathological changes associated to an absorbable fibrin patch (Tachosil®) covering in an experimental model of high-risk colonic anastomoses. Histol. Histopathol. 33, 299–306 (2017). PubMed

Anthis, A. H. C. et al. Chemically stable, strongly adhesive sealant patch for intestinal anastomotic leakage prevention. Adv. Funct. Mater. n/a, 2007099 (2021).

Li J, et al. Tough adhesives for diverse wet surfaces. Science. 2017;357:378–381. doi: 10.1126/science.aah6362. PubMed DOI PMC

Wu J, et al. An off-the-shelf bioadhesive patch for sutureless repair of gastrointestinal defects. Sci. Transl. Med. 2022;14:eabh2857. doi: 10.1126/scitranslmed.abh2857. PubMed DOI

Gao Z, Duan L, Yang Y, Hu W, Gao G. Mussel-inspired tough hydrogels with self-repairing and tissue adhesion. Appl. Surf. Sci. 2018;427:74–82. doi: 10.1016/j.apsusc.2017.08.157. DOI

Wu SJ, Yuk H, Wu J, Nabzdyk CS, Zhao X. A multifunctional origami patch for minimally invasive tissue sealing. Adv. Mater. 2021;33:2007667. doi: 10.1002/adma.202007667. PubMed DOI PMC

Kim K, Kim K, Ryu JH, Lee H. Chitosan-catechol: A polymer with long-lasting mucoadhesive properties. Biomaterials. 2015;52:161–170. doi: 10.1016/j.biomaterials.2015.02.010. PubMed DOI

Ito T, Eriguchi M, Koyama Y. Bioabsorbable bioadhesive hydrogel comprising poly(acrylic acid) and poly(vinylpyrrolidone) for adhesion barrier and hemostatic device. MRS Commun. 2015;5:291–295. doi: 10.1557/mrc.2015.14. DOI

Nam, S. & Mooney, D. Polymeric tissue adhesives. Chem. Rev. 10.1021/acs.chemrev.0c00798 (2021). PubMed

Pinnaratip R, Bhuiyan MSA, Meyers K, Rajachar RM, Lee BP. Multifunctional biomedical adhesives. Adv. Healthc. Mater. 2019;8:1801568. doi: 10.1002/adhm.201801568. PubMed DOI PMC

Kalidasan V, et al. Wirelessly operated bioelectronic sutures for the monitoring of deep surgical wounds. Nat. Biomed. Eng. 2021;5:1217–1227. doi: 10.1038/s41551-021-00802-0. PubMed DOI

Hellebrekers BWJ, Trimbos-Kemper GCM, van Blitterswijk CA, Bakkum EA, Trimbos JBMZ. Effects of five different barrier materials on postsurgical adhesion formation in the rat. Hum. Reprod. 2000;15:1358–1363. doi: 10.1093/humrep/15.6.1358. PubMed DOI

Singh B, Sharma K, Rajneesh, Dutt S. Dietary fiber tragacanth gum based hydrogels for use in drug delivery applications. Bioact. Carbohydr. Diet. Fibre. 2020;21:100208. doi: 10.1016/j.bcdf.2019.100208. DOI

Shapiro MG, et al. Biogenic gas nanostructures as ultrasonic molecular reporters. Nat. Nanotechnol. 2014;9:311–316. doi: 10.1038/nnano.2014.32. PubMed DOI PMC

Sirelkhatim A, et al. Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano-Micro Lett. 2015;7:219–242. doi: 10.1007/s40820-015-0040-x. PubMed DOI PMC

Yu J, et al. An ultrasoft self-fused supramolecular polymer hydrogel for completely preventing postoperative tissue adhesion. Adv. Mater. 2021;33:2008395. doi: 10.1002/adma.202008395. PubMed DOI

Zhao X, et al. An injectable and antifouling self-fused supramolecular hydrogel for preventing postoperative and recurrent adhesions. Chem. Eng. J. 2021;404:127096. doi: 10.1016/j.cej.2020.127096. DOI

Xu Z, Liu W. Poly(N -acryloyl glycinamide): a fascinating polymer that exhibits a range of properties from UCST to high-strength hydrogels. Chem. Commun. 2018;54:10540–10553. doi: 10.1039/C8CC04614J. PubMed DOI

Pawar AA, et al. High-performance 3D printing of hydrogels by water-dispersible photoinitiator nanoparticles. Sci. Adv. 2016;2:e1501381. doi: 10.1126/sciadv.1501381. PubMed DOI PMC

Taking Photoinitiators Into the Water World. Sigma-Aldrichhttps://www.sigmaaldrich.com/technical-documents/articles/technology-spotlights/watersoluble-photoinitiators.html.

Guan, Y. et al. An enhanced drought-tolerant method using SA-loaded pamps polymer materials applied on tobacco pelleted seeds. Sci. World J. 2014, (2014). PubMed PMC

Zhang X, Xu B, Gao F, Zheng P, Liu W. Repair of volumetric bone defects with a high strength BMP-loaded-mineralized hydrogel tubular scaffold. J. Mater. Chem. B. 2017;5:5588–5596. doi: 10.1039/C7TB01279A. DOI

Kovačič S, Silverstein MS. Superabsorbent, high porosity, pamps-based hydrogels through emulsion templating. Macromol. Rapid Commun. 2016;37:1814–1819. doi: 10.1002/marc.201600249. PubMed DOI

Pasquet J, et al. The contribution of zinc ions to the antimicrobial activity of zinc oxide. Colloids Surf. Physicochem. Eng. Asp. 2014;457:263–274. doi: 10.1016/j.colsurfa.2014.05.057. DOI

Matter MT, et al. Engineering the bioactivity of flame-made ceria and ceria/bioglass hybrid nanoparticles. ACS Appl. Mater. Interfaces. 2019;11:2830–2839. doi: 10.1021/acsami.8b18778. PubMed DOI

Siddiqi KS, Ur Rahman A, Tajuddin, Husen A. Properties of zinc oxide nanoparticles and their activity against microbes. Nanoscale Res. Lett. 2018;13:141. doi: 10.1186/s11671-018-2532-3. PubMed DOI PMC

Nussinovitch A, Velez‐Silvestre R, Peleg M. Mechanical properties of hydrocolloid gels filled with internally produced CO2 gas bubbles. Biotechnol. Prog. 1992;8:424–428. doi: 10.1021/bp00017a009. PubMed DOI

Darnell MC, et al. Performance and biocompatibility of extremely tough alginate/polyacrylamide hydrogels. Biomaterials. 2013;34:8042–8048. doi: 10.1016/j.biomaterials.2013.06.061. PubMed DOI PMC

Kvietys PR, Granger DN. Role of intestinal lymphatics in interstitial volume regulation and transmucosal water transport. Ann. N. Y. Acad. Sci. 2010;1207:E29–E43. doi: 10.1111/j.1749-6632.2010.05709.x. PubMed DOI PMC

Bar-Zion A, et al. Acoustically triggered mechanotherapy using genetically encoded gas vesicles. Nat. Nanotechnol. 2021;16:1403–1412. doi: 10.1038/s41565-021-00971-8. PubMed DOI

Kaur N, Narang A, Bansal AK. Use of biorelevant dissolution and PBPK modeling to predict oral drug absorption. Eur. J. Pharm. Biopharm. 2018;129:222–246. doi: 10.1016/j.ejpb.2018.05.024. PubMed DOI

F04 Committee. Test Method for Strength Properties of Tissue Adhesives in T-Peel by Tension Loading. http://www.astm.org/cgi-bin/resolver.cgi?F2256-05R1510.1520/F2256-05R15.

F04 Committee. Test Method for Strength Properties of Tissue Adhesives in Lap-Shear by Tension Loading. http://www.astm.org/cgi-bin/resolver.cgi?F2255-05R1510.1520/F2255-05R15.

Bergholt MS, et al. Raman spectroscopy reveals new insights into the zonal organization of native and tissue-engineered articular cartilage. ACS Cent. Sci. 2016;2:885–895. doi: 10.1021/acscentsci.6b00222. PubMed DOI PMC

Matter MT, et al. Multiscale analysis of metal oxide nanoparticles in tissue: insights into biodistribution and biotransformation. Adv. Sci. 2020;7:2000912. doi: 10.1002/advs.202000912. PubMed DOI PMC

Surgical Sealant with Integrated Shape-Morphing Dual Modality Ultrasound and Computed Tomography Sensors for Gastric Leak Detection