A Non-invasive, Closed-Loop Electronic Stent for Real-Time Management of Gastroesophageal Reflux Disease

Abstract

Gastroesophageal reflux disease (GERD) is a prevalent chronic condition that affects approximately 33% of the population and significantly increases the risk of esophageal cancer (5-year survival rate < 10%). Current pharmacological treatments cannot cure GERD, and surgical treatment often interferes with normal gastroesophageal physiology. Here, we developed a non-invasive transoral deliverable bioelectronic stent that enables real-time, closed-loop management of GERD without disrupting normal esophageal function. The stent is fabricated by an industrial weaving machine with functionalized fibers, followed by electroplating and chemical etching. It integrates vertically aligned multiple-channel pH/impedance fiber sensors for reflux detection and an electrical stimulator with pressure feedback. Owing to its shape-memory properties and low modulus, which is comparable to that of the woven structure of the esophagus, the stent is synchronized with esophageal motility without affecting physiological function. These sensing and electrical stimulation modules operate in a closed-loop fashion, where reflux-specific pH and impedance signals trigger LES stimulation, and the resulting contraction efficacy is immediately confirmed by a pressure sensor. In GERD animal models, the stent achieved 99.7% accuracy in reflux episode detection and successfully induced sphincter contraction in more than 95% of events, with negligible esophageal inflammation. This non-invasive, physiologically compatible, and closed-loop bioelectronic stent offers a novel solution for GERD management with real-time intervention for preventing disease progression and improving long-term outcomes.

Keywords

Fiber electronics / Bioelectronic stent / Gastroesophageal reflux disease / Closed-loop monitoring and stimulation

References

[1] Argüero J, Sifrim D. Pathophysiology of gastro-oesophageal reflux disease: implications for diagnosis and management. Nat Rev Gastroenterol Hepatol, 2024, 21: 282.

[2] Katzka DA, Kahrilas PJ. Advances in the diagnosis and management of gastroesophageal reflux disease. BMJ, 2020, 371. m3786

[3] Dodds WJ, Dent J, Hogan WJ, Helm JF, Hauser R, Patel GK, Egide MS. Mechanisms of gastroesophageal reflux in patients with reflux esophagitis. N Engl J Med, 1982, 307: 1547.

[4] Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, Laversanne M, Ferlay J, Arnold M. The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology, 2022, 163: 649.

[5] Mehta RS, Staller K, Chan AT. Review of gastroesophageal reflux disease. JAMA, 2021, 325: 1472.

[6] Carlsson R, Dent J, Watts R, Riley S, Sheikh R, Hatlebakk J, Haug K, de Groot G, van Oudvorst A, Dalväg A, Junghard O, Wiklund IInternational GORD Study Group. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. Eur J Gastroenterol Hepatol, 1998, 10: 119.

[7] Ganz RA, Peters JH, Horgan S, Bemelman WA, Dunst CM, Edmundowicz SA, Lipham JC, Luketich JD, Melvin WS, Oelschlager BK, Schlack-Haerer SC, Smith CD, Smith CC, Dunn D, Taiganides PA. Esophageal sphincter device for gastroesophageal reflux disease. N Engl J Med, 2013, 368: 719.

[8] Vakil N, Shaw M, Kirby R. Clinical effectiveness of laparoscopic fundoplication in a U.S. community. Am J Med, 2003, 114: 1.

[9] Benamouzig R, Uzzan B, Deyra J, Martin A, Girard B, Little J, Chaussade S. Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial. Gut, 2012, 61: 255.

[10] Bonavina L, DeMeester T, Fockens P, Dunn D, Saino G, Bona D, Lipham J, Bemelman W, Ganz RA. Laparoscopic sphincter augmentation device eliminates reflux symptoms and normalizes esophageal acid exposure: one- and 2-year results of a feasibility trial. Ann Surg, 2010, 252: 857.

[11] Gyawali CP, Yadlapati R, Fass R, Katzka D, Pandolfino J, Savarino E, Sifrim D, Spechler S, Zerbib F, Fox MR, Bhatia S, de Bortoli N, Cho YK, Cisternas D, Chen CL, Cock C, Hani A, Remes Troche JM, Xiao Y, Vaezi MF, Roman S. Updates to the modern diagnosis of GERD: Lyon consensus 2.0. Gut, 2024, 73: 361.

[12] Hungin APS, Molloy-Bland M, Scarpignato C. Revisiting Montreal: new insights into symptoms and their causes, and implications for the future of GERD. Am J Gastroenterol, 2019, 114: 414.

[13] Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut, 2012, 61: 1340.

[14] Vaezi MF, Shaheen NJ, Muthusamy VR. State of evidence in minimally invasive management of gastroesophageal reflux: findings of a scoping review. Gastroenterology, 2020, 159: 1504.

[15] Rodríguez L, Rodríguez P, Neto MG, Ayala JC, Saba J, Berel D, Conklin J, Soffer E. Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease. Neurogastroenterol Motil, 2012, 24: 446.

[16] Paireder M, Kristo I, Asari R, Jomrich G, Steindl J, Rieder E, Schoppmann SF. Electrical lower esophageal sphincter augmentation in patients with GERD and severe ineffective esophageal motility-a safety and efficacy study. Surg Endosc, 2019, 33: 3623.

[17] Borbély Y, Bouvy N, Schulz HG, Rodriguez LA, Ortiz C, Nieponice A. Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy. Surg Obes Relat Dis, 2018, 14: 611.

[18] Rodríguez L, Rodriguez PA, Gómez B, Netto MG, Crowell MD, Soffer E. Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: long-term 3-year results. Surg Endosc, 2016, 30: 2666.

[19] Rodríguez L, Rodriguez P, Gómez B, Ayala JC, Saba J, Perez-Castilla A, Galvao Neto M, Crowell MD. Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: final results of open-label prospective trial. Surg Endosc, 2013, 27: 1083.

[20] Rodríguez L, Rodriguez P, Gómez B, Ayala JC, Oksenberg D, Perez-Castilla A, Netto MG, Soffer E, Crowell MD. Long-term results of electrical stimulation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease. Endoscopy, 2013, 45: 595.

[21] Franks I. GERD: electrical stimulation of the lower esophageal sphincter to treat GERD. Nat Rev Gastroenterol Hepatol, 2012, 9: 190.

[22] Paireder M, Kristo I, Nikolic M, Jomrich G, Steindl J, Rieder E, Asari R, Schoppmann SF. Electrical stimulation therapy of the lower esophageal sphincter in GERD patients—a prospective single-center study. Eur Surg, 2021, 53: 29.

[23] Paireder M, Kristo I, Asari R, Jomrich G, Steindl J, Rieder E, Schoppmann SF. Effect of electrical stimulation therapy of the lower esophageal sphincter in GERD patients with ineffective esophageal motility. Surg Endosc, 2021, 35: 6101.

[24] Kappelle WF, Bredenoord AJ, Conchillo JM, Ruurda JP, Bouvy ND, van Berge Henegouwen MI, Chiu PW, Booth M, Hani A, Reddy DN, Bogte A, Smout AJ, Wu JC, Escalona A, Valdovinos MA, Torres-Villalobos G, Siersema PD. Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial. Aliment Pharmacol Ther, 2015, 42: 614.

[25] Banerjee R, Pratap N, Kalpala R, Reddy DN. Effect of electrical stimulation of the lower esophageal sphincter using endoscopically implanted temporary stimulation leads in patients with reflux disease. Surg Endosc, 2014, 28: 1003.

[26] Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol, 2022, 117: 27.

[27] Fass R, Boeckxstaens GE, El-Serag H, Rosen R, Sifrim D, Vaezi MF. Gastro-oesophageal reflux disease. Nat Rev Dis Primers, 2021, 7: 55.

[28] Wang L, Xie S, Wang Z, Liu F, Yang Y, Tang C, Wu X, Liu P, Li Y, Saiyin H, Zheng S, Sun X, Xu F, Yu H, Peng H. Functionalized helical fibre bundles of carbon nanotubes as electrochemical sensors for long-term in vivo monitoring of multiple disease biomarkers. Nat Biomed Eng, 2020, 4: 159.

[29] Wang L, Wang L, Zhang Y, Pan J, Li S, Sun X, Zhang B, Peng H. Weaving sensing fibers into electrochemical fabric for real-time health monitoring. Adv Funct Mater, 2018, 28. 1804456

[30] Shang J, Ma X, Zou P, Huang C, Lao Z, Wang J, Jiang T, Fu Y, Li J, Zhang S, Li R, Fan Y. A flexible catheter-based sensor array for upper airway soft tissues pressure monitoring. Nat Commun, 2025, 16: 287.

[31] Zhang B, Hu Y, Shi X, Li W, Zeng X, Liu F, Chen JDZ, Xie WF. Integrative effects and vagal mechanisms of transcutaneous electrical acustimulation on gastroesophageal motility in patients with gastroesophageal reflux disease. Am J Gastroenterol, 2021, 116: 1495.

[32] Li T, Feng ZQ, Qu M, Yan K, Yuan T, Gao B, Wang T, Dong W, Zheng J. Core/shell piezoelectric nanofibers with spatial self-orientated β-phase nanocrystals for real-time micropressure monitoring of cardiovascular walls. ACS Nano, 2019, 13: 10062.

[33] Kwon K, Kim JU, Won SM, Zhao J, Avila R, Wang H, Chun KS, Jang H, Lee KH, Kim JH, Yoo S, Kang YJ, Kim J, Lim J, Park Y, Lu W, Kim TI, Banks A, Huang Y, Rogers JA. A battery-less wireless implant for the continuous monitoring of vascular pressure, flow rate and temperature. Nat Biomed Eng, 2023, 7: 1215.

[34] Ni C, Chen D, Yin Y, Wen X, Chen X, Yang C, Chen G, Sun Z, Wen J, Jiao Y, Wang C, Wang N, Kong X, Deng S, Shen Y, Xiao R, Jin X, Li J, Kong X, Zhao Q, Xie T. Shape memory polymer with programmable recovery onset. Nature, 2023, 622: 748.

[35] Zhao T, Jiang H, Zhang K, Xu Y, Kang X, Xu J, Zhou X, Chen P, Peng H. Continuous preparation of high-performing carbon nanotube fibers based on cycloalkane/ethanol mixing carbon source. Acta Chim Sin, 2023, 81: 565.

[36] Feng J, Chen C, Sun X, Peng H. Implantable fiber biosensors based on carbon nanotubes. Acc Mater Res, 2021, 2: 138.

[37] Lee SH, Lee S. Fabrication and characterization of roll-to-roll-coated cantilever-structured touch sensors. ACS Appl Mater Interfaces, 2020, 12: 46797.

[38] Koo B-J, Shin Y-K, Kim S-M, Kim JI, Kim B, Jeong J, Seo M-H. Micromachined PVA (poly(vinyl alcohol)) sacrificial layer for facile and scalable demonstration of highly reproducible porous-type pressure sensor. ACS Appl Polym Mater, 2024, 6: 11788.

[39] Doucet BM, Lam A, Griffin L. Neuromuscular electrical stimulation for skeletal muscle function. Yale J Biol Med, 2012, 85: 201

[40] Neyroud D, Dodd D, Gondin J, Maffiuletti NA, Kayser B, Place N. Wide-pulse-high-frequency neuromuscular stimulation of triceps surae induces greater muscle fatigue compared with conventional stimulation. J Appl Physiol, 2014, 116: 1281.

[41] Rinsma NF, Bouvy ND, Masclee AA, Conchillo JM. Electrical stimulation therapy for gastroesophageal reflux disease. J Neurogastroenterol Motil, 2014, 20: 287.

[42] Shirzaei Sani E, Xu C, Wang C, Song Y, Min J, Tu J, Solomon SA, Li J, Banks JL, Armstrong DG, Gao W. A stretchable wireless wearable bioelectronic system for multiplexed monitoring and combination treatment of infected chronic wounds. Sci Adv, 2023, 9. eadf7388

[43] Li Q, Li D, Lu J, Zou K, Wang L, Jiao Y, Wang M, Gao R, Song J, Li Y, Li F, Ji J, Wang J, Li L, Ye T, He E, Chen H, Wang Y, Ren J, Bai C, Yang S, Zhang Y. Interface-stabilized fiber sensor for real-time monitoring of amniotic fluid during pregnancy. Adv Mater, 2024, 36. 2307726

[44] Funk LM, Zhang JY, Drosdeck JM, Melvin WS, Walker JP, Perry KA. Long-term cost-effectiveness of medical, endoscopic and surgical management of gastroesophageal reflux disease. Surgery, 2015, 157: 126.

Funding

National Natural Science Foundation of China(T2321003)

Ministry of Science and Technology of the People's Republic of China(2022YFA1203001)

Science and Technology Commission of Shanghai Municipality(24ZR1406700)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China

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