{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:10:13Z","timestamp":1776255013069,"version":"3.50.1"},"reference-count":43,"publisher":"Knowledge E DMCC","issue":"1","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["knepublishing.com"],"crossmark-restriction":true},"short-container-title":["IJRM"],"abstract":"<jats:p>Background: Endometrial-derived hydrogels are rich in extracellular matrix proteins as well as bioactive molecules that promote cell adhesion, proliferation, and angiogenesis.\r\nObjective: This study investigates the potential of recellularized human endometrial hydrogel, populated by mesenchymal cells, as a scaffold for mouse blastocyst implantation.\r\nMaterials and Methods: In this experimental study, we characterized the decellularization process of human endometrial tissue through morphological analysis, DNA quantification, and scanning electron microscopy. We then evaluated the morphology, ultrastructure, biocompatibility, biodegradation, and pH changes of the hydrogel incubated in phosphate-buffered saline. The hydrogel was recellularized with human endometrial mesenchymal cells, and mouse blastocysts were co-cultured on this recellularized hydrogel for 48 hr, observed via laser confocal scanning microscopy.\r\nResults: Morphological and ultrastructural examinations of the decellularized tissue revealed structures similar to native endometrium, while the absence of cells and nuclei, confirmed through morphological staining and DNA analysis, validated the success of the decellularization process. The hydrogel exhibited excellent biocompatibility according to the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay results, demonstrated an appropriate biodegradation rate in vitro, and showed no significant pH alteration. Mesenchymal cells successfully attached to the hydrogel scaffold, and mouse embryos adhered to and invaded the recellularized hydrogel.\r\nConclusion: This novel implantation model, which integrates human endometrial mesenchymal cells, endometrial hydrogel, and mouse embryos, has significant implications for reproductive research and clinical applications. However, further investigation is necessary to fully explore and optimize its potential.<\/jats:p>","DOI":"10.18502\/ijrm.v24i1.20994","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:24:21Z","timestamp":1774859061000},"page":"23-36","update-policy":"https:\/\/doi.org\/10.18502\/knecrossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Fabrication and characterization of decellularized human endometrial hydrogel as a scaffold for in vitro embryo implantation: An experimental study"],"prefix":"10.18502","volume":"24","author":[{"given":"Elham","family":"Sadeghi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyedsajad","family":"Moazzeni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojdeh","family":"Salehnia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7770","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"328325","doi-asserted-by":"crossref","unstructured":"[1] Rodr\u00edguez-Eguren A, Bueno-Fernandez C, G\u00f3mez-\u00c1lvarez M, Franc\u00e9s-Herrero E, Pellicer A, Bellver J, et al. Evolution of biotechnological advances and regenerative therapies for endometrial disorders: A systematic review. Hum Reprod Update 2024; 30: 584\u2013613.","DOI":"10.1093\/humupd\/dmae013"},{"key":"328326","doi-asserted-by":"crossref","unstructured":"[2] Yoshimasa Y, Takao T, Katakura S, Tomisato S, Masuda H, Tanaka M, et al. A decellularized uterine endometrial scaffold enhances regeneration of the endometrium in rats. Int J Mol Sci 2023; 24: 7605.","DOI":"10.3390\/ijms24087605"},{"key":"328327","doi-asserted-by":"crossref","unstructured":"[3] Franko R, Franko Y, Ribes Martinez E, Ferronato GA, Heinzelmann I, Grechi N, et al. Mechanical properties of native and decellularized reproductive tissues: Insights for tissue engineering strategies. Sci Rep 2024; 14: 7347.","DOI":"10.1038\/s41598-024-57867-5"},{"key":"328328","doi-asserted-by":"crossref","unstructured":"[4] Gnecco JS, Brown A, Buttrey K, Ives C, Goods BA, Baugh L, et al. Organoid co-culture model of the human endometrium in a fully synthetic extracellular matrix enables the study of epithelial-stromal crosstalk. Med 2023; 4: 554\u2013579.","DOI":"10.1016\/j.medj.2023.07.004"},{"key":"328329","doi-asserted-by":"crossref","unstructured":"[5] Peyton SR. Engineering the endometrium. Med 2023; 4: 495\u2013496.","DOI":"10.1016\/j.medj.2023.07.009"},{"key":"328330","doi-asserted-by":"crossref","unstructured":"[6] Shibata S, Endo Sh, Nagai LAE, Kobayashi EH, Oike A, Kobayashi N, et al. Modeling embryo-endometrial interface recapitulating human embryo implantation. Sci Adv 2024; 10: eadi4819.","DOI":"10.1126\/sciadv.adi4819"},{"key":"328331","doi-asserted-by":"crossref","unstructured":"[7] Olalekan SA, Burdette JE, Getsios S, Woodruff TK, Kim JJ. Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment. Biol Reprod 2017; 96: 971\u2013981.","DOI":"10.1093\/biolre\/iox039"},{"key":"328332","doi-asserted-by":"crossref","unstructured":"[8] Campo H, Garc\u00eda-Dom\u00ednguez X, L\u00f3pez-Mart\u00ednez S, Faus A, Vicente Ant\u00f3n JS, Marco-Jim\u00e9nez F, et al. Tissue-specific decellularized endometrial substratum mimicking different physiological conditions influences in vitro embryo development in a rabbit model. Acta Biomater 2019; 89: 126\u2013138.","DOI":"10.1016\/j.actbio.2019.03.004"},{"key":"328333","doi-asserted-by":"crossref","unstructured":"[9] Hellstr\u00f6m M, El-Akouri RR, Sihlbom C, Olsson BM, Lengqvist J, B\u00e4ckdahl H, et al. Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization. Acta Biomater 2014; 10: 5034\u20135042.","DOI":"10.1016\/j.actbio.2014.08.018"},{"key":"328334","doi-asserted-by":"crossref","unstructured":"[10] Sargazi Z, Zavareh S, Jafarabadi M, Salehnia M. An efficient protocol for decellularization of the human endometrial fragments for clinical usage. Prog Biomater 2021; 10: 119\u2013130.","DOI":"10.1007\/s40204-021-00156-5"},{"key":"328335","doi-asserted-by":"crossref","unstructured":"[11] Brown M, Li J, Moraes C, Tabrizian M, Li-Jessen NYK. Decellularized extracellular matrix: New promising and challenging biomaterials for regenerative medicine. Biomaterials 2022; 289: 121786.","DOI":"10.1016\/j.biomaterials.2022.121786"},{"key":"328336","doi-asserted-by":"crossref","unstructured":"[12] Moazzeni S, Demiryurek Y, Yu M, Shreiber DI, Zahn JD, Shan JW, et al. Single-cell mechanical analysis and tension quantification via electrodeformation relaxation. Phys Rev E 2021; 103: 032409.","DOI":"10.1103\/PhysRevE.103.032409"},{"key":"328337","doi-asserted-by":"crossref","unstructured":"[13] Santoso EG, Yoshida K, Hirota Y, Aizawa M, Yoshino O, Kishida A, et al. Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models. PloS One 2014; 9: e103201.","DOI":"10.1371\/journal.pone.0103201"},{"key":"328338","doi-asserted-by":"crossref","unstructured":"[14] Gilpin A, Yang Y. Decellularization strategies for regenerative medicine: From processing techniques to applications. BioMed Res Int 2017; 2017: 9831534.","DOI":"10.1155\/2017\/9831534"},{"key":"328339","unstructured":"[15] Sadeghi E, Rezazadeh Valojerdi M, Salehnia M. Co-culture of mouse blastocysts on a human recellularized endometrial scaffold: An in vitro model for future implantation studies. Cell J 2023; 25: 579\u2013590."},{"key":"328340","doi-asserted-by":"crossref","unstructured":"[16] L\u00f3pez-Mart\u00ednez S, Rodr\u00edguez-Eguren A, de Miguel-G\u00f3mez L, Franc\u00e9s-Herrero E, Faus A, D\u00edaz A, et al. Bioengineered endometrial hydrogels with growth factors promote tissue regeneration and restore fertility in murine models. Acta Biomater 2021; 135: 113\u2013125.","DOI":"10.1016\/j.actbio.2021.08.025"},{"key":"328341","doi-asserted-by":"crossref","unstructured":"[17] Jamaluddin MFB, Ghosh A, Ingle A, Mohammed R, Ali A, Bahrami M, et al. Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues. Proc Natl Acad Sci U S A 2022; 119: e2208040119.","DOI":"10.1073\/pnas.2208040119"},{"key":"328342","doi-asserted-by":"crossref","unstructured":"[18] G\u00f3mez-\u00c1lvarez M, Bueno-Fernandez C, Rodr\u00edguez-Eguren A, Franc\u00e9s-Herrero E, Agustina-Hern\u00e1ndez M, Faus A, et al. Hybrid endometrial-derived hydrogels: Human organoid culture models and in vivo perspectives. Adv Healthc Mater 2024; 13: e2303838.","DOI":"10.1002\/adhm.202303838"},{"key":"328343","doi-asserted-by":"crossref","unstructured":"[19] Franc\u00e9s-Herrero E, Ju\u00e1rez-Barber E, Campo H, L\u00f3pez-Mart\u00ednez S, de Miguel-G\u00f3mez L, Faus A, et al. Improved models of human endometrial organoids based on hydrogels from decellularized endometrium. J Pers Med 2021; 11: 504.","DOI":"10.3390\/jpm11060504"},{"key":"328344","doi-asserted-by":"crossref","unstructured":"[20] Cai G, Hou Z, Sun W, Li P, Zhang J, Yang L, et al. Recent developments in biomaterial-based hydrogel as the delivery system for repairing endometrial injury. Front Bioeng Biotechnol 2022; 10: 894252.","DOI":"10.3389\/fbioe.2022.894252"},{"key":"328345","doi-asserted-by":"crossref","unstructured":"[21] Li X, Li P, Wang C, Shang T, Han H, Tong Y, et al. A thermo-sensitive and injectable hydrogel derived from a decellularized amniotic membrane to prevent intrauterine adhesion by accelerating endometrium regeneration. Biomat Sci 2022; 10: 2275\u20132286.","DOI":"10.1039\/D1BM01791H"},{"key":"328346","unstructured":"[22] Salehnia M, Moazzeni S. Emerging frontiers in ovarian organoids: Bridging development, function, and disease. Int J Fertil Steril 2026; 2: 80\u201394."},{"key":"328347","doi-asserted-by":"crossref","unstructured":"[23] L\u00f3pez-Mart\u00ednez S, Campo H, de Miguel-G\u00f3mez L, Faus A, Navarro AT, D\u00edaz A, et al. A Natural xenogeneic endometrial extracellular matrix hydrogel toward improving current human in vitro models and future in vivo applications. Front Bioeng Biotechnol 2021; 9: 639688.","DOI":"10.3389\/fbioe.2021.639688"},{"key":"328348","doi-asserted-by":"crossref","unstructured":"[24] Sargazi Z, Zavareh S, Salehnia M. Differentiation of human endometrial mesenchymal cells to epithelial and stromal cells by seeding on the decellularized endometrial scaffold. In Vitro Cell Dev Biol Anim 2023; 59: 443\u2013454.","DOI":"10.1007\/s11626-023-00779-x"},{"key":"328349","doi-asserted-by":"crossref","unstructured":"[25] Zhu X, Yu F, Yan G, Hu Y, Sun H, Ding L. Human endometrial perivascular stem cells exhibit a limited potential to regenerate endometrium after xenotransplantation. Hum Reprod 2021; 36: 145\u2013159.","DOI":"10.1093\/humrep\/deaa261"},{"key":"328350","doi-asserted-by":"crossref","unstructured":"[26] Sun B, Cheng X, Wu Q. The endometrial stem\/progenitor cells and their niches. Stem Cell Rev Rep 2024; 20: 1273\u20131284.","DOI":"10.1007\/s12015-024-10725-3"},{"key":"328351","doi-asserted-by":"crossref","unstructured":"[27] Hong IS. Endometrial stem cells: Orchestrating dynamic regeneration of endometrium and their implications in diverse endometrial disorders. 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Reprod Biomed Online 2017; 35: 241\u2013252.","DOI":"10.1016\/j.rbmo.2017.05.020"},{"key":"328356","doi-asserted-by":"crossref","unstructured":"[32] Ojosnegros S, Seriola A, Godeau AL, Veiga A. Embryo implantation in the laboratory: An update on current techniques. Hum Reprod Update 2021; 27: 501\u2013530.","DOI":"10.1093\/humupd\/dmaa054"},{"key":"328357","doi-asserted-by":"crossref","unstructured":"[33] Zhang D, Du Q, Li C, Ding C, Chen J, He Y, et al. Functionalized human umbilical cord mesenchymal stem cells and injectable HA\/Gel hydrogel synergy in endometrial repair and fertility recovery. Acta Biomater 2023; 167: 205\u2013218.","DOI":"10.1016\/j.actbio.2023.06.013"},{"key":"328358","doi-asserted-by":"crossref","unstructured":"[34] Simsa R, Padma AM, Heher P, Hellstr\u00f6m M, Teuschl A, Jenndahl L, et al. Systematic in vitro comparison of decellularization protocols for blood vessels. PLoS One 2018; 13: e0209269.","DOI":"10.1371\/journal.pone.0209269"},{"key":"328359","doi-asserted-by":"crossref","unstructured":"[35] Saldin LT, Cramer MC, Velankar SS, White LJ, Badylak SF. Extracellular matrix hydrogels from decellularized tissues: Structure and function. Acta Biomater 2017; 49: 1\u201315.","DOI":"10.1016\/j.actbio.2016.11.068"},{"key":"328360","doi-asserted-by":"crossref","unstructured":"[36] Kort-Mascort J, Flores-Torres S, Peza-Chavez O, Jang JH, Pardo LA, Tran SD, et al. Decellularized ECM hydrogels: Prior use considerations, applications, and opportunities in tissue engineering and biofabrication. Biomater Sci 2023; 11: 400\u2013431.","DOI":"10.1039\/D2BM01273A"},{"key":"328361","doi-asserted-by":"crossref","unstructured":"[37] Jafarkhani S, Amiri E, Moazzeni S, Zohoorian-Abootorabi T, Eftekhary M, Aminnezhad S, et al. Exploring the effects of micro-nano surface topography on MG63 osteoblast-like cell responses: An in vitro study. Colloids Surfaces A: Physicochem Eng Aspects 2023; 675: 131872.","DOI":"10.1016\/j.colsurfa.2023.131872"},{"key":"328362","doi-asserted-by":"crossref","unstructured":"[38] Liu C, Pei M, Li Q, Zhang Y. Decellularized extracellular matrix mediates tissue construction and regeneration. Front Med 2022; 16: 56\u201382.","DOI":"10.1007\/s11684-021-0900-3"},{"key":"328363","doi-asserted-by":"crossref","unstructured":"[39] Khakbiz M, Chagami M, Sheibani S, Amiri E, Moazzeni S, Shakibania S, et al. Enhancement of corrosion, biocompatibility and drug delivery properties of nitinol implants surface by Al-Zn-LDH nanohybrids. Colloids Surfaces A: Physicochem Eng Aspects 2025; 704: 135524.","DOI":"10.1016\/j.colsurfa.2024.135524"},{"key":"328364","doi-asserted-by":"crossref","unstructured":"[40] Moazzeni S, Kyker-Snowman K, Cohen RI, Wang H, Li R, Shreiber DI, et al. N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex. Sci Rep 2025; 15: 4296.","DOI":"10.1038\/s41598-025-88537-9"},{"key":"328365","doi-asserted-by":"crossref","unstructured":"[41] Salisbury E, Rawlings TM, Efstathiou S, Tryfonos M, Makwana K, Fitzgerald HC, et al. Photo-cross-linked gelatin methacryloyl hydrogels enable the growth of primary human endometrial stromal cells and epithelial gland organoids. ACS Appl Mater Interfaces 2024; 16: 39140\u201339152.","DOI":"10.1021\/acsami.4c08763"},{"key":"328366","doi-asserted-by":"crossref","unstructured":"[42] Zambuto SG, Clancy KBH, Harley BAC. A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion. Interface Focus 2019; 9: 20190016.","DOI":"10.1098\/rsfs.2019.0016"},{"key":"328367","doi-asserted-by":"crossref","unstructured":"[43] Kim YY, Park K-H, Kim YJ, Kim MS, Liu HC, Rosenwaks Z, et al. Synergistic regenerative effects of functionalized endometrial stromal cells with hyaluronic acid hydrogel in a murine model of uterine damage. 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