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While traditional therapeutic approaches provide some regulation of bone homeostasis, they often present limitations and adverse effects. In orthopedic procedures, bone cement serves as a crucial material for stabilizing osteoporotic bone and securing implants. However, with the exception of magnesium phosphate cement, most cement variants lack substantial bone regenerative properties. Recent developments in biomaterial science have opened new avenues for enhancing bone cement functionality through innovative modifications. These advanced materials demonstrate promising capabilities in modulating the bone microenvironment through their distinct physicochemical properties. This review provides a systematic analysis of contemporary biomaterial-based modifications of bone cement, focusing on their influence on the bone healing microenvironment. The discussion begins with an examination of bone microenvironment pathology, followed by an evaluation of various biomaterial modifications and their effects on cement properties. The review then explores regulatory strategies targeting specific microenvironmental elements, including inflammatory response, oxidative stress, osteoblast-osteoclast homeostasis, vascular network formation, and osteocyte-mediated processes. The concluding section addresses current technical challenges and emerging research directions, providing insights for the development of next-generation biomaterials with enhanced functionality and therapeutic potential.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12951-025-03363-5","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T01:21:29Z","timestamp":1747099289000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Biomaterial-based strategies for bone cement: modulating the bone microenvironment and promoting regeneration"],"prefix":"10.1186","volume":"23","author":[{"given":"Jiawei","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"3363_CR1","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1007\/s40265-021-01625-8","volume":"81","author":"AC van der Burgh","year":"2021","unstructured":"van der Burgh AC, de Keyser CE, Zillikens MC, Stricker BH. 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