{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:11:03Z","timestamp":1784776263285,"version":"3.55.0"},"reference-count":195,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Fracture nonunion or delayed union remains a significant clinical problem that burdens both the patient and the healthcare system. Defined as failure for bone to unite 9 months post injury or 3 months with no progression toward union, the pathology of nonunion may require multiple surgical interventions with associated morbidity. Increasing evidence has highlighted that nonunion is a multifaceted problem, not only a result of mechanical failure, but also a product of persistent dysregulation of the osteoimmune microenvironment manifested as impaired osteogenesis and bone healing. While current approaches focus on enhanced fixation and various bone grafting strategies, these treatments often fail to coordinate healing with osteoimmune regulation. This review summarizes the emerging biologic and bioengineering approaches that target osteoimmunology to enhance fracture repair. Scaffold systems, including metals, bioceramics, hydrogels, and micro\/nanoparticle formulations, are being increasingly engineered to provide structural support while directing macrophage polarization and stimulating osteogenic signaling. We also review cell-based therapies and gene-modified constructs that are being developed to introduce osteoimmunology cues that halt chronic inflammation and promote an osteogenic microenvironment.<\/jats:p>","DOI":"10.3390\/bioengineering13020223","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:11:28Z","timestamp":1771240288000},"page":"223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Osteoimmunologic Basis of Biologic and Bioengineered Scaffolds in Fracture Healing"],"prefix":"10.3390","volume":"13","author":[{"given":"Hannah","family":"Shelby","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bergren","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Wier","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-9698","authenticated-orcid":false,"given":"Edward M.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-8929","authenticated-orcid":false,"given":"Jay R.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1146\/annurev.immunol.24.021605.090646","article-title":"Osteoimmunology: Interplay between the Immune System and Bone Metabolism","volume":"24","author":"Walsh","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41577-019-0178-8","article-title":"Osteoimmunology: Evolving Concepts in Bone\u2013Immune Interactions in Health and Disease","volume":"19","author":"Tsukasaki","year":"2019","journal-title":"Nat. Rev. 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