{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:26:27Z","timestamp":1789683987184,"version":"4.0.1"},"reference-count":118,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bone regeneration is a highly coordinated, multistep process governed by interactions among skeletal cells, immune components, and the vascular system. Although bone exhibits an intrinsic capacity for self\u2010repair, critical\u2010sized defects caused by trauma, tumor resection, infection, or chronic diseases often exceed this regenerative potential and necessitate therapeutic intervention. Conventional bone tissue engineering strategies have predominantly focused on promoting osteogenesis and angiogenesis; however, their limited clinical translation indicates that essential regulatory mechanisms remain insufficiently addressed. Advances in osteoimmunology have revealed that immune responses\u2014particularly the initiation, intensity, and resolution of early inflammation\u2014play an instructive role in determining bone healing outcomes. In parallel, exosomes have emerged as mediators of intercellular communication, capable of transferring bioactive cargos that regulate immune cell polarization, angiogenesis, and osteogenic differentiation. Integrating exosomes with biomaterial scaffolds has led to the concept of osteoimmunoengineering, in which scaffolds are designed not only to provide mechanical support but also to modulate the immune microenvironment in a spatiotemporally controlled manner. This review systematically discusses how exosome\u2010functionalized biomaterials can reprogram immune responses to enhance bone regeneration. We outline the immune landscape of bone healing, highlighting key immune cell populations and cytokine signaling pathways involved in inflammation resolution and tissue reconstruction. We also examine immunomodulatory mechanisms of exosomes, material\u2010based strategies for regulating exosome immobilization and release kinetics, and major translational challenges, including exosome heterogeneity, manufacturing standardization, and clinical product classification.<\/jats:p>","DOI":"10.1002\/bit.70315","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:56:58Z","timestamp":1784271418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteoimmunoengineering With Exosome\u2010Functionalized Biomaterials: Rewriting the Immune\u2013Bone Regeneration Interface"],"prefix":"10.1002","author":[{"given":"Asrin","family":"Emami","sequence":"first","affiliation":[{"name":"Iranian Tissue Bank and Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-1512","authenticated-orcid":false,"given":"Iman Menbari","family":"Oskouie","sequence":"additional","affiliation":[{"name":"Urology Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"7","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.70113","article-title":"Defining the Parameters for Sorting of RNA Cargo Into Extracellular Vesicles","volume":"14","author":"Abdelgawad A.","year":"2025","journal-title":"Journal of Extracellular Vesicles"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cobme.2020.100248","article-title":"Bone Tissue Engineering Techniques, Advances and Scaffolds for Treatment of Bone Defects","volume":"17","author":"Alonzo M.","year":"2021","journal-title":"Current Opinion in Biomedical Engineering"},{"issue":"17","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"8669","DOI":"10.3390\/ijms26178669","article-title":"Beyond Killing: The Overlooked Contribution of Neutrophils to Tissue Repair","volume":"26","author":"Anitua E.","year":"2025","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2025.142271","article-title":"Accelerated Healing of Full\u2010Thickness Skin Wounds by Multifunctional Exosome\u2010Loaded Scaffolds of Alginate Hydrogel\/PCL Nanofibers With Hemostatic Efficacy","volume":"307","author":"Ashrafi F.","year":"2025","journal-title":"International Journal of Biological Macromolecules"},{"issue":"1","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s40779-024-00564-1","article-title":"Tackling Exosome and Nuclear Receptor Interaction: An Emerging Paradigm in the Treatment of Chronic Diseases","volume":"11","author":"Aswani B. 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