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Despite decades of investigation, controversy still exists surrounding the definition of CSDs, with criteria varying across species, experimental models, and patient populations. This review integrates past and contemporary perspectives, while examining how age, dura mater biology, and stem cell dynamics influence regenerative potential. For instance, pediatric patients demonstrate increased healing capacity due to their metabolically active dura and enriched stem cell niches, while aging patients face diminished osteogenesis due to chronic age\u2010related inflammation (inflammaging) and stem cell senescence. Meanwhile, experimental models highlight that defect size, embryonic bone origin, and proximity to cranial sutures affect healing, thus highlighting the need for standardized, age\u2010specific definitions of CSDs. Advances in biomaterials, like bioceramic composites and dura\u2010integrative hydrogels, show promise in advancing osteogenesis and vascularization across age groups. Additionally, dura\u2010targeted regenerative strategies that leverage dural signaling represent a novel and promising solution to cranial repair. However, the transition from translational to clinical practice remains limited due to the lack of standardization in the literature and scarce long\u2010term clinical data. In this review, CSD re\u2010classification is proposed through an age\u2010stratified framework that integrates biological, structural, and clinical variables. Standardizing models will help isolate determinants of calvarial healing and refine treatment strategies.<\/jats:p>","DOI":"10.1002\/jbm.b.70107","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:05:28Z","timestamp":1780981528000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Controversies Surrounding Critical\u2010Size Defects: Influence of Age and Biological Characteristics"],"prefix":"10.1002","volume":"114","author":[{"given":"Andrew","family":"Nordlund","sequence":"first","affiliation":[{"name":"University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Shah","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Florida International University Herbert Wertheim College of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Mirsky","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashyap K.","family":"Tadisina","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Division of Plastic Surgery University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo J.","family":"Rios\u2010Diaz","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Division of Plastic Surgery University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-0339","authenticated-orcid":false,"given":"Vasudev Vivekanand","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Dr. John T. 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