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Updated: Jun 13, 2026
Large-Scale Preparation of Synovial Fluid Mesenchymal Stem Cell-Derived Exosomes by 3D Bioreactor Culture
Published on: July 26, 2022
3D-printed PCL/nHA/SA/COL loaded with M2 macrophage-derived exosomes alleviates the senescence of bone marrow
Lu Yin1, Honglan Huang2, Jianyu Zhu2
1Department of Stomatology, Stomatological Hospital of Xiamen Medical College, Xiamen, Fujian 361008, China; Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Stomatological Hospital of Xiamen Medical College, Xiamen, Fujian 361003, China; Engineering Research Center of Stomatological Biomaterials, Fujian Province University, Xiamen Medical College, Xiamen, Fujian 361023, China.
Background:
The communication between bone marrow mesenchymal stem cells (BMSCs) and macrophages in implant microenvironment is crucial for implantation prognosis. This study explores the potential of PCL/nHA/SA/COL loaded with M2 macrophage-derived exosomes (PCL/nHA/SA/COL@EXOs) on the functions of BMSCs.
Methods:
PCL/nHA/SA/COL structure is generated by 3D printing. M2 macrophage-derived exosomes (EXOs) are analyzed by TEM and NTR. Gene expression is determined by RT-qPCR, Western blot, and immunofluorescence. KDM4B-induced WNT/P53 signaling-controlled transcription was analyzed using ChIP assay. Cellular behaviors of BMSCs were analyzed by CCK-8, EdU, alizarin red staining, ALP staining, and SAβ-gal staining. 3D-printed PCL/nHA/SA/COL@Exo implantation is performed in mice as well as aged rats.
Results:
PCL/nHA/SA/COL@EXOs exerts more remarkable effects on promoting the proliferation and osteogenic differentiation of BMSCs. Furthermore, PCL/nHA/SA/COL@EXOs inhibits the senescence of BMSCs. Mechanistically, PCL/nHA/SA/COL@EXOs upregulates KDM4B, which mediates histone demethylation and drives WNT/P53 signaling-controlled transcription. In vivo assays confirm that PCL/nHA/SA/COL@EXOs inhibits senescence and mediates new bone regeneration.
Conclusion:
PCL/nHA/SA/COL@EXOs effectively inhibits BMSC senescence as well as endows with bone integration performance, which holds great potential for future clinical applications.
