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Microphysiological systems (MPS), including organ\u2010on\u2010chip and organoid\u2010on\u2010chip platforms, have emerged as transformative human\u2010relevant technologies capable of recapitulating organ\u2010level structure, function, and disease dynamics under precisely controlled microenvironments. By integrating advances in microfabrication, biomaterials, stem cell and organoid biology, microfluidics, and real\u2010time sensing, MPS enables physiologically faithful modeling of tissue interfaces, mechanical forces, metabolic processes, and inter\u2010organ communication. Recent progress has led to robust organ\u2010specific platforms, interconnected multi\u2010organ systems, and body\u2010on\u2010chip models that support systemic pharmacokinetic and pharmacodynamic studies. Concurrently, regulatory recognition through the FDA Modernization Acts and accelerating international standardization efforts have positioned MPS as a validated new approach for drug development and safety assessment. Despite these advances, challenges related to cell sourcing, tissue heterogeneity, scalability, statistical rigor, and protocol standardization remain. This review synthesizes the technological foundations, biological applications, regulatory landscape, and emerging challenges of MPS, emphasizing the need to quantify and harness biological heterogeneity rather than eliminate it.<\/jats:p>","DOI":"10.1002\/bit.70229","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T10:13:18Z","timestamp":1778062398000},"page":"1929-1941","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Microphysiological Systems: Transforming Biomedical and Clinical Research"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4114-9461","authenticated-orcid":false,"given":"Om Saswat","family":"Sahoo","sequence":"first","affiliation":[{"name":"Department of Biochemistry All India Institute of Medical Sciences New Delhi New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4521-1897","authenticated-orcid":false,"given":"Avisha","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry All India Institute of Medical Sciences New Delhi New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-2007","authenticated-orcid":false,"given":"Aparna K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology All India Institute of Medical Sciences New Delhi New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0259-9881","authenticated-orcid":false,"given":"Gurpreet Singh","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Biochemistry All India Institute of Medical Sciences New Delhi New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3600-6554","authenticated-orcid":false,"given":"Ruby","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry All India Institute of Medical Sciences New Delhi New Delhi India"},{"name":"Department of Biochemistry Kasturba Medical College, Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-8729","authenticated-orcid":false,"given":"Subhradip","family":"Karmakar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry All India Institute of Medical Sciences New Delhi New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"A new ISO Subcommittee to develop standards for Organ\u2010on\u2010Chip2025b.EURL ECVAM"},{"key":"e_1_2_13_3_1","unstructured":"A new ISO Subcommittee to develop standards for Organ\u2010on\u2010Chip.2025. 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