{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:42:22Z","timestamp":1792186942982,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Spermatogenesis relies on the highly specialized interaction between germ cells and a supportive somatic niche, yet replicating this environment in vitro remains a major challenge. Primary human Sertoli cells (hSCs), key architects of this niche, often lose their phenotype under conventional culture conditions, limiting the establishment of a stable blood\u2010testis barrier (BTB)\u2010associated phenotype and their ability to support germ cells. Here, we present a structurally organized, human ECM\u2010derived connective tissue equivalent (CTE) designed to support long\u2010term maintenance and organization of hSCs in vitro. The CTE, generated from fibroblast\u2010secreted matrix enriched in laminin, fibronectin, and collagen IV, reproduces key biochemical and physical features of a supportive microenvironment. hSCs introduced into the CTE as single cells or pre\u2010formed spheroids were evaluated for survival, structural organization, phenotypic stability, and ECM remodeling. Both configurations supported progressive expression and organization of BTB\u2010associated proteins (ZO\u20101, OCLDN) together with upregulation of Sertoli cell\u2010associated markers, including SOX9 and ABP, with the spheroid\u2010based model showing improved structural cohesion, integration within the construct, and more evident junctional organization over time. Overall, this bioactive human\u2010derived platform supports long\u2010term maintenance of hSC phenotype and barrier\u2010associated features in vitro, providing a promising basis for future human testis models and co\u2010culture studies.<\/jats:p>","DOI":"10.1002\/adhm.202505848","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:29:47Z","timestamp":1777015787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tuning the Testicular Microenvironment for Enhancing Human Sertoli Cells Maturation and Functionality In Vitro"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2354-8509","authenticated-orcid":false,"given":"Annachiara","family":"Scalzone","sequence":"first","affiliation":[{"name":"Center For Advanced Biomaterials For Healthcare (CABHC) Istituto Italiano di Tecnologia  Naples 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