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Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages. While transient inflammation is an essential trigger for tissue healing following an injury, sustained inflammation (e.g., in foreign body response to implants, diabetes or inflammatory diseases) can hinder tissue healing and cause tissue damage. Modulating macrophage polarization has emerged as an effective strategy for enhancing immune-mediated tissue regeneration and promoting better integration of implantable materials in the host. This article provides an overview of macrophages\u2019 functional properties followed by discussing different strategies for modulating macrophage polarization. Advances in the use of synthetic and natural biomaterials to fabricate immune-modulatory materials are highlighted. This reveals that the development and clinical application of more effective immunomodulatory systems targeting macrophage polarization under pathological conditions will be driven by a detailed understanding of the factors that regulate macrophage polarization and biological function in order to optimize existing methods and generate novel strategies to control cell phenotype.<\/jats:p>","DOI":"10.3390\/ijms25137278","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3034-6699","authenticated-orcid":false,"given":"Qiran","family":"Du","sequence":"first","affiliation":[{"name":"Immuno-Bioengineering Group, School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Medical School, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pruthvi","family":"Nakuleswaran","sequence":"additional","affiliation":[{"name":"Medical School, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Maghami","sequence":"additional","affiliation":[{"name":"Hull York Medical School, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7914-6662","authenticated-orcid":false,"given":"Savindu","family":"Alagoda","sequence":"additional","affiliation":[{"name":"Medical School, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7756-8444","authenticated-orcid":false,"given":"Andrew L.","family":"Hook","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3160-8759","authenticated-orcid":false,"given":"Amir M.","family":"Ghaemmaghami","sequence":"additional","affiliation":[{"name":"Immuno-Bioengineering Group, School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.tcb.2005.09.002","article-title":"Inflammatory cells during wound repair: The good, the bad and the ugly","volume":"15","author":"Martin","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.immuni.2014.10.008","article-title":"Leukocyte migration into inflamed tissues","volume":"41","author":"Nourshargh","year":"2014","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in Tissue Repair, Regeneration, and Fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.imbio.2013.09.001","article-title":"Macrophages: Supportive cells for tissue repair and regeneration","volume":"219","author":"Chazaud","year":"2014","journal-title":"Immunobiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/intimm\/dxy054","article-title":"Macrophages in inflammation, repair and regeneration","volume":"30","author":"Oishi","year":"2018","journal-title":"Int. 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