The use of ex vivo, in vitro models, microfluidic devices, tissue engineering technologies, the determination of their ethical and deontological components in experimental studies of Crohn's disease and other inflammatory bowel diseases
DOI:
https://doi.org/10.15574/PS.2025.4(89).109122Keywords:
Crohn's disease, inflammatory bowel diseases, experimental studies, microfluidics, ex vivo models, in vitro models, tissue engineering, deontology, ethicsAbstract
Experimental studies of current issues of Crohn's disease (CD) and other inflammatory bowel diseases (IBD) are due to the increase in morbidity, the presence of unclear etiological factors, many links in pathogenesis, the lack of effective comprehensive treatment, preventive measures for the occurrence of diseases and the prevention of its surgical complications.
Aim - to determine the technological efficiency, compliance with ethical and deontological requirements, practical significance, specificity, effectiveness and prospects for using ex vivo, in vitro models, microfluidic devices, tissue engineering technologies (TET) in experimental studies of current issues of CD and other IBD.
Various in vivo studies have certain physiological, ethical and translational limitations, which forces scientists to imp lement new methods of experimental search, relying on the development of modern technologies. According to the results of scientific literature search, ex vivo, in vitro models are characterized, the use of microfluidic devices and TET is highlighted, the main provisions and problematic issues of the ethical and deontological component of experimental studies of Crohn's disease and other IBD are given. The advantages, disadvantages, and practical significance of experimental systems are presented.
Conclusions. The use of in vitro and ex vivo models provides the opportunity to reproduce and study physiological, pathological processes with a high level of specificity. The use of TET and microfluidics technologies allows to reduce the number of experimental animals. The use of human biological samples requires strict adherence to ethical, deontological and legal norms. The introduction of microfluidic devices and robotic platforms ensures high efficiency in the development of targeted therapy methods, determination and prediction of the therapeutic effect of medical drugs, research of physiological and pathological processes in Crohn's disease and other IBD. The integration of microfluidic systems with artificial intelligence and robotic platforms, the use of biological hydrogels and 3D-bioprinting technology allows the creation of multi-organ networks for relatively long-term experimental studies of IBD, registration and analysis of their results without violating the integrity of the experimental system.
The author declares that there is no conflict of interest.
References
Afshar L, Aghayan HR, Sadighi J, Arjmand B, Hashemi SM, Basiri M et al. (2020). Ethics of research on stem cells and regenerative medicine: ethical guidelines in the Islamic Republic of Iran. Stem Cell Res Ther. 11(1): 396. https://doi.org/10.1186/s13287-020-01916-z; PMid:32928295 PMCid:PMC7489032
Alvites RD, Branquinho MV, Sousa AC, Lopes B, Sousa P, Mendonça C et al. (2021). Small Ruminants and Its Use in Regenerative Medicine: Recent Works and Future Perspectives. Biology (Basel). 10(3): 249. https://doi.org/10.3390/biology10030249; PMid:33810087 PMCid:PMC8004958
Baptiste DL, Caviness-Ashe N, Josiah N, Commodore-Mensah Y, Arscott J et al. (2022). Henrietta Lacks and America's dark history of research involving African Americans. Nurs Open. 9(5): 2236-2238. https://doi.org/10.1002/nop2.1257; PMid:35700235 PMCid:PMC9374392
Botti G, Di Bonito M, Cantile M. (2021). Organoid biobanks as a new tool for pre-clinical validation of candidate drug efficacy and safety. Int J Physiol Pathophysiol Pharmacol. 13(1): 17-21. URL: https://pubmed.ncbi.nlm.nih.gov/33815668/.
Clua-Ferré L, Suau R, Vañó-Segarra I, Ginés I, Serena C, Manyé J. (2024). Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles: A focus on inflammatory bowel disease. Clin Transl Med. 14(11): e70075. https://doi.org/10.1002/ctm2.70075; PMid:39488745 PMCid:PMC11531661
Cruz Rivera S, Aiyegbusi OL, Ives J, Draper H, Mercieca-Bebber R, Ells C et al. (2022). Ethical Considerations for the Inclusion of Patient-Reported Outcomes in Clinical Research: The PRO Ethics Guidelines. Jama. 327(19): 1910-1919. https://doi.org/10.1001/jama.2022.6421; PMid:35579638 PMCid:PMC10026781
De Gregorio V, Sgambato C, Urciuolo F, Vecchione R, Netti PA, Imparato G. (2022). Immunoresponsive microbiota-gut-on-chip reproduces barrier dysfunction, stromal reshaping and probiotics translocation under inflammation. Biomaterials. 286: 121573. https://doi.org/10.1016/j.biomaterials.2022.121573; PMid:35617781
De Kanter AJ, Jongsma KR, Verhaar MC, Bredenoord AL. (2023). The Ethical Implications of Tissue Engineering for Regenerative Purposes: A Systematic Review. Tissue Eng Part B Rev. 29(2): 167-187. https://doi.org/10.1089/ten.teb.2022.0033; PMid:36112697 PMCid:PMC10122262
Dubinina VO, Ksonz IV, Bilash SM, Abyzova LV, Bilanov OS, Ksonz VI. (2023). Axiological dimensions of medical deontology in pediatric surgery. Paediatric Surgery (Ukraine). 4(81): 108-113; https://doi.org/10.15574/PS.2023.81.108
Eder MM. (2023). Aligning clinical research ethics with community-engaged and participatory research in the United States. Front Public Health. 11: 1122479. https://doi.org/10.3389/fpubh.2023.1122479; PMid:37213625 PMCid:PMC10192870
Garreta E, Kamm RD, Chuva de Sousa Lopes SM, Lancaster MA, Weiss R, Trepat X et al. (2021). Rethinking organoid technology through bioengineering. Nat Mater. 20(2): 145-155. https://doi.org/10.1038/s41563-020-00804-4; PMid:33199860
Gazzaniga FS, Camacho DM, Wu M, Silva Palazzo MF, Dinis ALM, Grafton FN et al. (2021). Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection. Front Cell Infect Microbiol. 11: 638014. https://doi.org/10.3389/fcimb.2021.638014; PMid:33777849 PMCid:PMC7996096
Gijzen L, Marescotti D, Raineri E, Nicolas A, Lanz HL, Guerrera D et al. (2020). An Intestine-on-a-Chip Model of Plug-and-Play Modularity to Study Inflammatory Processes. SLAS Technol. 25(6): 585-597. https://doi.org/10.1177/2472630320924999; PMid:32576063 PMCid:PMC7684793
Grand View Research. (2025). Microfluidics Market Size, Share & Trends Analysis Report By Technology, By Product (Microfluidic-based Devices, Microfluidic Components), By Material (Silicon, Glass), By Application (Medical, Non-Medical), By Region, And Segment Forecasts, 2025-2030. URL: https://www.grandviewresearch.com/industry-analysis/microfluidics-market 119.
Grupp TM, Rusch S, Massin P, Blom A, Garcia-Rey E, Cristofolini L et al. (2023). 1st EFORT European Consensus "Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices": Background, Delphi Methodology & Consensus process. EFORT Open Rev. 8(7): 499-508. https://doi.org/10.1530/EOR-23-0054; PMid:37395678 PMCid:PMC10321049
Guo Y, Chen X, Gong P, Li G, Yao W, Yang W. (2023). The Gut-Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology. Int J Mol Sci. 24(4): 4089. https://doi.org/10.3390/ijms24044089; PMid:36835499 PMCid:PMC9962350
Jacques E, Suuronen EJ. (2020). The Progression of Regenerative Medicine and its Impact on Therapy Translation. Clin Transl Sci. 13(3): 440-450. https://doi.org/10.1111/cts.12736; PMid:31981408 PMCid:PMC7214652
Jongsma KR, Bredenoord AL. (2020). Ethics parallel research: an approach for (early) ethical guidance of biomedical innovation. BMC Med Ethics. 21(1): 81. https://doi.org/10.1186/s12910-020-00524-z; PMid:32867753 PMCid:PMC7461257
Joshi A, SoniA, Acharya S. (2022). In vitro models and ex vivo systems used in inflammatory bowel disease. In vitro Model. 1(3): 213-227. https://doi.org/10.1007/s44164-022-00017-w; PMid:37519330 PMCid:PMC9036838
Justus CR, Marie MA, Sanderlin EJ, Yang LV. (2023). Transwell In vitro Cell Migration and Invasion Assays. Methods Mol Biol. 2644: 349-359. https://doi.org/10.1007/978-1-0716-3052-5_22; PMid:37142933 PMCid:PMC10335869
Kenney RM, Loeser A, Whitman NA, Lockett MR. (2018). Paper-based Transwell assays: an inexpensive alternative to study cellular invasion. Analyst. 144(1): 206-211. https://doi.org/10.1039/C8AN01157E; PMid:30328422 PMCid:PMC6296866
Kim HJ, Lee J, Choi JH, Bahinski A, Ingber DE. (2016). Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device. J Vis Exp. (114): 54344. https://doi.org/10.3791/54344
Klein L, Hutmacher DW. (2024). Straddling the Line Between In vitro and Ex vivo Investigations. Tissue Eng Part C Methods. 30(10): 443-451. https://doi.org/10.1089/ten.tec.2024.0246; PMid:39422880
Kriaa A, Mariaule V, De Rudder C, Jablaoui A, Sokol H, Wilmes P et al. (2024). From animal models to gut-on-chip: the challenging journey to capture inter-individual variability in chronic digestive disorders. Gut Microbes. 16(1): 2333434. https://doi.org/10.1080/19490976.2024.2333434; PMid:38536705 PMCid:PMC10978023
Li XG, Chen MX, Zhao SQ, Wang XQ. (2022). Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip. Stem Cell Rev Rep. 18(6): 2137-2151. https://doi.org/10.1007/s12015-021-10205-y; PMid:34181185 PMCid:PMC8237043
Macedo MH, Dias Neto M, Pastrana L, Gonçalves C, Xavier M. (2023). Recent Advances in Cell-Based In vitro Models to Recreate Human Intestinal Inflammation. Adv Sci (Weinh). 10(31): e2301391. https://doi.org/10.1002/advs.202301391; PMid:37736674 PMCid:PMC10625086
Malaguarnera G, Graute M, Homs Corbera A. (2021). The translational roadmap of the gut models, focusing on gut-on-chip. Open Res Eur. 1: 62. https://doi.org/10.12688/openreseurope.13709.2; PMid:37645178 PMCid:PMC10445823
Mangione F, Salmon B, EzEldeen M, Jacobs R, Chaussain C, Vital S. (2022). Characteristics of Large Animal Models for Current Cell-Based Oral Tissue Regeneration. Tissue Eng Part B Rev. 28(3): 489-505. https://doi.org/10.1089/ten.teb.2020.0384; PMid:33882717
Morelli M, Cabezuelo Rodríguez M, Queiroz K. (2024). A high-throughput gut-on-chip platform to study the epithelial responses to enterotoxins. Sci Rep. 14(1): 5797. https://doi.org/10.1038/s41598-024-56520-5; PMid:38461178 PMCid:PMC10925042
Morelli M, Kurek D, Ng CP, Queiroz K. (2023). Gut-on-a-Chip Models: Current and Future Perspectives for Host-Microbial Interactions Research. Biomedicines. 11(2): 619. https://doi.org/10.3390/biomedicines11020619; PMid:36831155 PMCid:PMC9953162
Novak R, Ingram M, Marquez S, Das D, Delahanty A, Herland A et al. (2020). Robotic fluidic coupling and interrogation of multiple vascularized organ chips. Nat Biomed Eng. 4(4): 407-420. https://doi.org/10.1038/s41551-019-0497-x; PMid:31988458 PMCid:PMC8057865
Oerlemans AJ, van Hoek ME, van Leeuwen E, Dekkers WJ. (2014). Hype and expectations in tissue engineering. Regen Med. 9(1): 113-122. https://doi.org/10.2217/rme.13.89; PMid:24351011
Rahman S, Ghiboub M, Donkers JM, van de Steeg E, van Tol EAF et al. (2021). The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip. Int J Mol Sci. 22(24): 13472. https://doi.org/10.3390/ijms222413472; PMid:34948271 PMCid:PMC8709104
Schenke-Layland K, Nerem RM. (2011). In vitro human tissue models--moving towards personalized regenerative medicine. Adv Drug Deliv Rev. 63(4-5): 195-196. https://doi.org/10.1016/j.addr.2011.05.001; PMid:21600252
Shevchenko YeV, Hladkykh FV, Matvieienko MS. (2024) Cryomedical biotechnologies as a key to effective decellularization in the creation of scaffolds for vascular transplantation. The Journal of V.N. Karazin Kharkiv National University. Series Medicine. 32; 3(50): 366-386. https://doi.org/10.26565/2313-6693-2024-50-08
Shevchenko YV, Liadova TI, Hladkykh FV, Matvieienko MS, Chyzh MO, Komorovsky RR. (2024). Decellularized Matrix Scaffolds for Vascular Transplantation: Addressing Immunogenicity, Sterilization, and Current Strategies for Long-Term Storage. Ukrainian Journal of Cardiovascular Surgery. 32(4): 78-90. https://doi.org/10.30702/ujcvs/24.32(04)/ShL061-7890
Shi Q, Carrillo JC, Penman MG, Manton J, Fioravanzo E, Powrie RH et al. (2022). Assessment of the Intestinal Absorption of Higher Olefins by the Everted Gut Sac Model in Combination with In Silico New Approach Methodologies. Chem Res Toxicol. 35(8): 1383-1392. https://doi.org/10.1021/acs.chemrestox.2c00089; PMid:35830964 PMCid:PMC9382673
Shin YC, Shin W, Koh D, Wu A, Ambrosini YM, Min S et al. (2020). Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. Micromachines (Basel). 11(7): 663. https://doi.org/10.3390/mi11070663; PMid:32645991 PMCid:PMC7408321
Soleiko DS, Prytula VP. (2025). In vivo experimental models in scientific research on current issues of Crohn's disease and other inflammatory bowel diseases. Paediatric Surgery (Ukraine). 3(88): 135-148. https://doi.org/10.15574/PS.2025.3(88).135148
Stoyeva TV, Dzhahiashvili OV, Melnychenko MH, Hudz VA. (2019). Using mathematical modeling in the differential diagnosis of acute abdominal syndrome in children. Paediatric surgery. Ukraine. 1(62): 47-52. https://doi.org/10.15574/PS.2019.62.47
Taylor WJ, Willink R, O'Connor DA, Patel V, Bourne A, Harris IA et al. (2023). Which clinical research questions are the most important? Development and preliminary validation of the Australia & New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network Research Question Importance Tool (ANZMUSC-RQIT). PLoS One. 18(3): e0281308. https://doi.org/10.1371/journal.pone.0281308; PMid:36930668 PMCid:PMC10022765
Thomas DP, Zhang J, Nguyen NT, Ta HT. (2023). Microfluidic Gut-on-a-Chip: Fundamentals and Challenges. Biosensors (Basel). 13(1): 136. https://doi.org/10.3390/bios13010136; PMid:36671971 PMCid:PMC9856111
Ungaro F, Garlatti V, Massimino L, Spinelli A, Carvello M, Sacchi M et al. (2019). mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn's Disease. Cells. 8(8): 924. https://doi.org/10.3390/cells8080924; PMid:31426584 PMCid:PMC6721646
Vera D, García-Díaz M, Torras N, Castillo Ó, Illa X, Villa R et al. (2024). A 3D bioprinted hydrogel gut-on-chip with integrated electrodes for transepithelial electrical resistance (TEER) measurements. Biofabrication. 16(3). https://doi.org/10.1088/1758-5090/ad3aa4; PMid:38574551
World Health Organization (WHO). (2020). Global health estimates 2019: estimated deaths by age, sex, and cause. Geneva, Switzerland.
Xiang Y, Wen H, Yu Y, Li M, Fu X, Huang S. (2020). Gut-on-chip: Recreating human intestine in vitro. J Tissue Eng. 11: 2041731420965318. https://doi.org/10.1177/2041731420965318; PMid:33282173 PMCid:PMC7682210
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Paediatric Surgery (Ukraine)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “PAEDIATRIC SURGERY. UKRAINE” is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license(СС BY-NC).
Authors transfer the copyright to the Journal “PAEDIATRIC SURGERY.UKRAINE” when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.
