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Coaxial electrospinning was employed to construct a scaffold with silk fibroin (SF)\/polycaprolactone (PCL)\/kaempferol (KAE) as the shell and icariin (ICA) as the core, preparing nanofibrous scaffolds (ICA@SF\/PCL\/KAE). Comprehensive characterizations confirmed the co-axial structure of the nanofibers and successful drug loading and favorable release profiles of KAE and ICA, as well as the significantly enhanced mechanical performance. The KAE-loaded scaffold exerted outstanding antibacterial activity, while all of the drug-containing scaffolds maintained excellent cytocompatibility. In LPS-induced inflammatory environments, macrophages co-cultured on KAE-containing scaffolds exhibited markedly reduced reactive oxygen species and nitric oxide production, along with a decreased M1 macrophage ratio and an increased M2 macrophage ratio. RT-PCR results demonstrated that KAE-loaded scaffolds downregulated pro-inflammatory gene expression and upregulated anti-inflammatory gene expression. In vitro osteogenic induction revealed that the incorporation of KAE and ICA, especially ICA, remarkably enhanced osteogenic activity of the nanofibrous scaffolds. Under inflammatory conditions, KAE-containing scaffolds exhibited superior regulation of the osteogenic immune microenvironment compared with ICA-containing scaffolds. Notably, the ICA@SF\/PCL\/KAE scaffold containing both components achieved the optimal performance in all of the above in vitro experiments. Finally, rat cranial defect experiments further verified the excellent osteogenic efficacy of ICA@SF\/PCL\/KAE in vivo. Collectively, the ICA@SF\/PCL\/KAE core\u2013shell nanofibrous scaffold offers an innovative approach for clinical bone defect treatment and expands the application potential of natural herbal active substances.<\/jats:p>","DOI":"10.1021\/acsami.6c12632","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:02:39Z","timestamp":1790618559000},"source":"Crossref","is-referenced-by-count":0,"title":["Silk Fibroin\/Polycaprolactone Coaxial Nanofibrous Scaffold Loaded with Kaempferol and Icariin: A Bioactive Macromolecular Platform for Bone Regeneration through Enhanced Antibacterial Activity and Osteoimmunomodulation"],"prefix":"10.1021","author":[{"given":"Yuhui","family":"Liu","sequence":"first","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhou","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Guan","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Meng","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Yu","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-5663","authenticated-orcid":true,"given":"Quanli","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7285-7893","authenticated-orcid":true,"given":"Qunlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6343-440X","authenticated-orcid":true,"given":"Xianwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, PR China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guomin","family":"Wu","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"583","key":"2026092814015281400_cit1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb4416","article-title":"BMPR1A maintains skeletal stem cell properties in craniofacial development and craniosynostosis","volume":"13","author":"Maruyama","year":"2021","journal-title":"Sci. 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