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In this study, a ternary composite scaffold composed of PCL-nHA-nMgO (PHM) was fabricated using 3D printing technology. After surface modification with a photothermal polydopamine (PDA) coating, a PHM@PDA composite scaffold was obtained. Metformin (Met) and PDA were loaded into GelMA hydrogels to produce GPM hydrogels. The GPM hydrogels were then packed into the PHM@PDA composite scaffolds, resulting in near-infrared region-I (NIR-I)-responsive PHM@PDA\/GPM composite scaffolds. The outer GPM layer serves as a three-dimensional in vivo-like microenvironment, providing physical transport channels for cellular nutrient exchange. Upon stimulation by NIR-I, the scaffold enables the dynamic release of Mg2+ and Met, upregulates the expression of the VEGF and KDR, accelerates vascular network reconstruction, and creates a mild microenvironment conducive to cell proliferation. Furthermore, by activating the PI3K\/AKT signaling pathway, it promotes the expression of osteogenesis-related factors (such as transcription factor Sp7, alkaline phosphatase, and osteocalcin), thereby accelerating the osteogenic differentiation process. In vivo animal experiments, micro-CT and tissue staining confirmed that, under near-infrared light (NIR-I) stimulation, this scaffold significantly increased bone mineral density, trabecular bone thickness, and trabecular bone count and demonstrated excellent angiogenic effects. In summary, this NIR-I-responsive composite scaffold can meet the dual requirements of reconstructing the vascular network and promoting osteogenic differentiation, enabling personalized precision therapy and offering a promising new treatment strategy for complex bone defects where vascular regeneration and osteogenic differentiation are challenging.<\/jats:p>","DOI":"10.1021\/acsami.6c09109","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:01:57Z","timestamp":1786946517000},"page":"44984-45002","source":"Crossref","is-referenced-by-count":0,"title":["Near-Infrared Region I-Responsive Composite Scaffolds Promote Bone Defect Repair by Jointly Regulating Angiogenic and Osteogenic Differentiation through Magnesium Ions and Metformin"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0939-0668","authenticated-orcid":true,"given":"Shuaihang","family":"Wang","sequence":"first","affiliation":[{"name":"China University of Mining and Technology , , ,","place":["Xuzhou, China, 221116"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Ji","sequence":"additional","affiliation":[{"name":"China University of Mining and Technology , , ,","place":["Xuzhou, China, 221116"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Shen","sequence":"additional","affiliation":[{"name":"China University of Mining and Technology , , ,","place":["Xuzhou, China, 221116"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Moer Acoustic Technology Research Institute Co., Ltd. , ,","place":["Xuzhou, China, 221116"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-4178","authenticated-orcid":true,"given":"Jingbin","family":"Hao","sequence":"additional","affiliation":[{"name":"China University of Mining and Technology , , ,","place":["Xuzhou, China, 221116"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Xuzhou Central Hospital, Southeast University , , ,","place":["Xuzhou, Jiangsu, China, 221009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Jia","sequence":"additional","affiliation":[{"name":"Xuzhou Clinical College Affiliated to Xuzhou Medical University , , ,","place":["Xuzhou, Jiangsu, China, 221004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Guo","sequence":"additional","affiliation":[{"name":"Xuzhou Central Hospital, Southeast University , , ,","place":["Xuzhou, Jiangsu, China, 221009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shang","sequence":"additional","affiliation":[{"name":"Xuzhou Central Hospital, Southeast University , , ,","place":["Xuzhou, Jiangsu, China, 221009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-3847","authenticated-orcid":true,"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"China University of Mining and Technology , , ,","place":["Xuzhou, China, 221116"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Han","sequence":"additional","affiliation":[{"name":"Xuzhou Central Hospital, Southeast University , , ,","place":["Xuzhou, Jiangsu, China, 221009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"issue":"8","key":"2026091814071528900_cit1","doi-asserted-by":"publisher","DOI":"10.1002\/smsc.202370015","article-title":"A review of advanced biomaterials and cells for the production of bone organoid","volume":"3","author":"Li","year":"2023","journal-title":"Small Sci."},{"issue":"17","key":"2026091814071528900_cit2","doi-asserted-by":"publisher","first-page":"21672","DOI":"10.1021\/acsami.4c03024","article-title":"Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis","volume":"16","author":"Li","year":"2024","journal-title":"ACS Appl. 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