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The purpose of this study is to clarify whether the HAp\/DN gel surface can differentiate the bone marrow\u2010derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum\u2010supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp\/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (<jats:italic>TGF\u2010\u03b21<\/jats:italic>,<jats:italic>BMP\u20102<\/jats:italic>,<jats:italic>Runx2<\/jats:italic>,<jats:italic>Col\u20101, ALP<\/jats:italic>,<jats:italic>OPN<\/jats:italic>,<jats:italic>BSP<\/jats:italic>, and<jats:italic>OCN)<\/jats:italic>in the cultured MSCs at 7\u2009days than the PS surfaces (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except for<jats:italic>Runx2<\/jats:italic>. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp\/DN gel surface than in the other three material surfaces (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Thirdly, when the HAp\/DN gel plug was implanted into the rabbit bone marrow, MSC marker\u2010positive cells were recruited in the tissue generated around the plug at 3\u2009days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp\/DN gel surface can differentiate the MSCs into osteogenic cells.<\/jats:p>","DOI":"10.1002\/jbm.a.37324","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T03:57:59Z","timestamp":1635479879000},"page":"747-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hydroxyapatite\u2010hybridized double\u2010network hydrogel surface enhances differentiation of bone marrow\u2010derived mesenchymal stem cells to osteogenic cells"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-699X","authenticated-orcid":false,"given":"Takuma","family":"Kaibara","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Hokkaido University Graduate School of Medicine Sapporo Japan"},{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University Sapporo 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