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Hydrogels, serving as an ideal candidate to mimic the organic matrix in bio\u2010tissues, can be strengthened by the direct introduction of minerals. However, this enhancement often comes at the expense of toughness due to interfacial mismatch. This study reveals that extreme toughening of hydrogels can be realized through simultaneous in situ mineralization and salting\u2010out, without the need for special chemical modification or additional reinforcements. The key to this strategy lies in harnessing the kosmotropic and precipitation behavior of specific anions as they penetrate a hydrogel system containing both anion\u2010sensitive polymers and multivalent cations. The resulting mineralized hydrogels demonstrate significant improvements in fracture stress, fracture energy, and fatigue threshold due to a multiscale energy dissipation mechanism, with optimal values reaching 12\u00a0MPa, 49\u00a0kJ\u00a0m\n                    <jats:sup>\u22122<\/jats:sup>\n                    , and 2.98\u00a0kJ\u00a0m\n                    <jats:sup>\u22122<\/jats:sup>\n                    . This simple strategy also proves to be generalizable to other anions, resulting in tough hydrogels with osteoconductivity for promoting in vitro mineralization of human adipose\u2010derived mesenchymal stem cells. This work introduces a universal route to toughen hydrogels without compromising other parameters, holding promise for biological applications demanding integrated mechanical properties.\n                  <\/jats:p>","DOI":"10.1002\/smll.202403322","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T02:21:30Z","timestamp":1718850090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An Organic\u2013Inorganic Hydrogel with Exceptional Mechanical Properties via Anion\u2010Induced Synergistic Toughening for Accelerating Osteogenic Differentiation"],"prefix":"10.1002","volume":"20","author":[{"given":"Hongmei","family":"Luo","sequence":"first","affiliation":[{"name":"College of Polymer Science and Engineering Sichuan University  Chengdu 610065 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