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Human foetal femoral and calvarial osteoblasts were encapsulated in a semi\u2010synthetic thiol\u2010modified hyaluronan gelatin polyethylene glycol diacrylate (PEGDA) cross\u2010linked HyStemC hydrogel. Constructs were subjected to a cyclic compressive strain of 33.4\u00a0kPa force every second for 5 s every hour for 6 h per day using FlexCell BioPress culture plates and compared to non\u2010compressed constructs. Cell viability, mineralisation, and morphological changes were observed over 21 days. <jats:italic>BMP2, ALP<\/jats:italic>, <jats:italic>COL1A1, COL2A1<\/jats:italic>, and <jats:italic>OCN<\/jats:italic> gene expression levels were quantified. Encapsulated osteoblast numbers increased and formed hydroxyapatite over a 21\u2010day period. Cell viability decreased under a cyclical strain when compared to cells under no strain. Femoral osteoblasts under strain expressed increased levels of <jats:italic>BMP2<\/jats:italic> (53.9\u2010fold) and <jats:italic>COL1A1<\/jats:italic> (5.1\u2010fold) mRNA compared to no strain constructs. Surprisingly, no <jats:italic>BMP2<\/jats:italic> mRNA was detected in calvarial osteoblasts. Osteoblasts derived from endochondral (femoral) and intra\u2010membranous (calvarial) processes behaved differently in 3D\u2010constructs. We therefore recommend that site\u2010specific osteoblasts be used for future bone engineering and bone replacement materials and further research undertaken to elucidate how site\u2010specific osteoblasts respond to cyclic compressive loads.<\/jats:p>","DOI":"10.1111\/eos.12818","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T17:41:16Z","timestamp":1626889276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential behaviour and gene expression in 3D cultures of femoral\u2010 and calvarial\u2010derived human osteoblasts under a cyclic compressive mechanical load"],"prefix":"10.1111","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5079-6287","authenticated-orcid":false,"given":"Yana","family":"Itskovich","sequence":"first","affiliation":[{"name":"Sir John Walsh Research Institute, Faculty of Dentistry University of Otago  Dunedin New 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