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To effectively repair bone defect, it is important to decrease excessive inflammation, enhance the differentiation of mesenchymal stem cells into osteoblasts, and stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), and gelatin (GEL) scaffolds were produced using 3D printing technology and pioglitazone (PIO)-containing polylactic acid\u2013glycolic acid (PLGA) nanospheres were added. In both in vitro and in vivo studies, material scaffolds with PIO-loaded polylactic acid\u2013glycolic acid nanospheres could reduce the inflammatory response by encouraging macrophage polarization from M1 to M2 and promoting the osteogenic differentiation of BMSCs by activating the BMP2\/Smad\/RUNX2 signal pathway to repair bone defects. The vascularization of human umbilical vein endothelial cells (HUVECs) through the PI3K\/AKT\/HIF1-\/VEGF pathway was also encouraged. In vivo research using PIO-containing PLGA nanospheres revealed massive collagen deposition in skin models. These findings indicate a potentially effective scaffold for bone healing, when PLGA nanospheres\u2014which contain the drug PIO\u2014are combined with ATP\/PVA\/GEL scaffolds.<\/jats:p>","DOI":"10.1177\/20417314241231452","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T04:58:25Z","timestamp":1707886705000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Regulation of the immune microenvironment by pioglitazone-loaded polylactic glycolic acid nanosphere composite scaffolds to promote vascularization and bone regeneration"],"prefix":"10.1177","volume":"15","author":[{"given":"Shijie","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Affiliated Changzhou Second People\u2019s Hospital of Nanjing Medical University, Changzhou, China"},{"name":"Changzhou Medical Center, Nanjing Medical University, Changzhou, 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