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This study compares material\u2010induced MNCs to cytokine\u2010induced MNCs using both in vitro and in vivo models. 3D\u2010embedded Raw264.7 cells and rat bone marrow\u2010derived monocytes (BMDMs), with or without cytokines such as IL\u20104 and RANKL, were characterized for their MNC morphologies and subtypes via in situ immunocytochemistry and flow cytometry. Macrophage polarization and osteoclastic differentiation were assessed through NO production, arginase activity, and tartrate\u2010resistant acid phosphatase levels. 3D matrix\u2010induced MNCs expressed the same phenotypic heterogeneity as the IL\u20104 and RANK\u2010treated ones. 3D matrix\u2010induced MNCs displayed the same phenotypic heterogeneity as those treated with IL\u20104 and RANKL. A high viscoelastic matrix (1006.48\u2009\u00b1\u200992.29\u2009Pa) induced larger populations of proinflammatory and osteoclast\u2010like MNCs, whereas a low viscoelastic matrix (38.61\u2009\u00b1\u20097.56\u2009Pa) supported active differentiation and gene expression across pro\u2010, anti\u2010inflammatory, and osteoclast\u2010like macrophages. Matrix viscoelasticity also influenced the effects of IL\u20104 and RANKL on macrophage\u2010derived MNC polarization. In an in vivo subcutaneous implantation model, medium to high viscoelastic matrices exhibited higher populations of CD86+ and RANK+ MNCs, while low viscoelastic matrices showed higher populations of CD206+ MNCs. These findings suggest that matrix viscoelasticity modulates macrophage differentiation and MNC phenotype, with low viscoelastic matrices potentially favoring anti\u2010inflammatory MNCs and macrophage differentiation suitable for subcutaneous implantation.<\/jats:p>","DOI":"10.1002\/jbm.a.37814","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T04:16:03Z","timestamp":1729484163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Viscoelastic Hydrogel Modulates Phenotype of Macrophage\u2010Derived Multinucleated Cells and Macrophage Differentiation in Foreign Body Reactions"],"prefix":"10.1002","volume":"113","author":[{"given":"Josephine Y.","family":"Fang","sequence":"first","affiliation":[{"name":"Nimni\u2010Cordoba Tissue Engineering and Drug Discovery Laboratory, Departments of Surgery, Keck School of Medicine University of Southern California  Los Angeles USA"},{"name":"Department of Craniofacial Biology, Herman Ostrow School of Dentistry University of Southern California  Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yang","sequence":"additional","affiliation":[{"name":"Nimni\u2010Cordoba Tissue Engineering and Drug Discovery Laboratory, Departments of Surgery, Keck School of Medicine University of Southern California  Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"M.C. Gill Composites Center University of Southern California  Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ba Xuan","family":"Hoang","sequence":"additional","affiliation":[{"name":"Nimni\u2010Cordoba Tissue Engineering and Drug Discovery Laboratory, Departments of Surgery, Keck School of Medicine University of Southern California  Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-4265","authenticated-orcid":false,"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"Nimni\u2010Cordoba Tissue Engineering and Drug Discovery Laboratory, Departments of Surgery, Keck School of Medicine University of Southern California  Los Angeles USA"},{"name":"Department of Biomedical Enginnering Viterbi School of Engineering, University of Southern California  Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.5999\/aps.2016.43.1.40"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(88)80204-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2017.0242"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.873226"},{"issue":"4","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/1097-4636(20010615)55:4<661::AID-JBM1061>3.0.CO;2-F","article-title":"Influence of Biomaterial Surface Chemistry on the Apoptosis of Adherent Cells","volume":"55","author":"Brodbeck W. 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