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Recreating this complexity in vitro has remained elusive. Here, we present a developmentally inspired, dual\u2010gradient 3D\u2010printed construct that unites native\u2010like stiffness and metabolic microenvironments to drive spatially resolved regeneration and model osteoarthritis in a phase\u2010specific manner. Human bone marrow\u2010derived mesenchymal stem cell spheroids are placed in soft, hypoxic niches to promote chondrogenesis, and in stiff, vascular\u2010rich regions to induce osteogenesis\u2014preserving cartilage\u2013bone crosstalk within one platform. This integration of gradients amplifies extracellular matrix formation beyond single\u2010cue designs through the synergistic effect of porosity and stiffness. Furthermore, its anisotropic architecture maintains cartilage\u2013bone crosstalk and allows drug response assessment, highlighting its potential as a physiologically relevant platform for osteoarthritis modeling and therapy screening. By bridging functional regeneration with preclinical drug screening, this model offers a physiologically relevant translational platform for advancing both osteochondral repair and disease research.<\/jats:p>","DOI":"10.1002\/advs.202516602","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:36:49Z","timestamp":1772959009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developmentally Inspired, Mechanical\u2013Metabolic Dual Gradient Osteochondral Constructs Bridging Regeneration and Therapeutic Screening"],"prefix":"10.1002","volume":"13","author":[{"given":"Yurim","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering Pohang University of Science and Technology (POSTECH)  Pohang Republic of 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