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Therefore, substitute synthetic bone grafts are required. This study aims to develop a cryogenic 3D-printed PLGA\/HA@SeNPs scaffold that synergistically regulates macrophage polarization and osteogenic differentiation for bone regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using low-temperature 3D printing combined with freeze-drying technology, a hierarchically porous PLGA\/HA@SeNPs composite scaffold was fabricated by compositing poly(lactic-co-glycolic acid) (PLGA) with hyaluronic acid-modified selenium (Se) nanoparticles (HA@SeNPs), enabling sustained immunomodulation and osteogenic activity through its engineered microtopography and bioactive components.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro evaluations confirmed that the unique microstructure and sustained Se release from HA@SeNPs synergistically promoted macrophage polarization toward the M2 phenotype, accompanied by enhanced osteogenic differentiation as shown by upregulation of Runx2 and osteocalcin and accelerated matrix mineralization. Implantation into a rat femoral critical-sized defect model resulted in substantially improved bone repair and architectural restoration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings indicate that the intrinsic physicochemical properties of the PLGA\/HA@SeNPs scaffold orchestrate a favorable osteo-immune environment, positioning it as a promising platform for bone regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/burnst\/tkag049","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T11:39:52Z","timestamp":1784979592000},"source":"Crossref","is-referenced-by-count":1,"title":["Cryogenic 3D-printed PLGA\/nano-selenium scaffold for bone regeneration: a dual-functional strategy synergistically regulating macrophage polarization and osteogenic differentiation"],"prefix":"10.1093","volume":"14","author":[{"given":"Shengwen","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing, 400016 ,","place":["China"]},{"name":"Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine , No. 1 Youyi Road, Yuzhong District, Chongqing, 400016 ,","place":["China"]},{"name":"Orthopedic Research Laboratory of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing, 400016 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing, 400016 ,","place":["China"]},{"name":"Chongqing 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