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Inspired by the discovery that the expression of magnesium transporter\u20101 (MagT1), a selective magnesium (Mg) transporter, is significantly upregulated in the endochondral ossification region of mouse embryos, a Mg\u2010enriched 3D culture system is proposed to provide an embryonic\u2010like environment for stem cells. First, the optimum concentration of Mg ions (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ) for creating the osteogenic microenvironment is screened by evaluating MagT1 expression levels, which correspond to the osteogenic differentiation capacity of stem cells. The results reveal that Mg\n                    <jats:sup>2+<\/jats:sup>\n                    selectively activates the mitogen\u2010activated protein kinase\/extracellular regulated kinase (MAPK\/ERK) pathway to stimulate osteogenic differentiation, and Mg\n                    <jats:sup>2+<\/jats:sup>\n                    influx via MagT1 is profoundly involved in this process. Then, Mg\u2010enriched microspheres are fabricated at the appropriate size to ensure the viability of the encapsulated cells. A series of experiments show that the Mg\u2010enriched microenvironment not only stimulates the osteogenic differentiation of stem cells but also promotes neovascularization. Obvious vascularized bone regeneration is achieved in vivo using these Mg\u2010enriched cell delivery vehicles. The findings suggest that biomaterials mimicking the developmental microenvironment might be promising tools to enhance tissue regeneration.\n                  <\/jats:p>","DOI":"10.1002\/advs.201900209","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T04:59:48Z","timestamp":1555563588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":157,"title":["A Magnesium\u2010Enriched 3D Culture System that Mimics the Bone Development Microenvironment for Vascularized Bone Regeneration"],"prefix":"10.1002","volume":"6","author":[{"given":"Sihan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Prosthodontics Shanghai Engineering Research Center of Advanced Dental Technology and Materials Shanghai Research Institute of Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Ninth People's Hospital College of Stomatology Shanghai JiaoTong University School of Medicine  639 Zhizaoju Road Shanghai 200011 P. 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