期刊
NANO TODAY
卷 43, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101401
关键词
Bone defect; Magnetic hyperthermia; Heat shock protein; PI3K/Akt pathway; Osteogenesis
资金
- National Natural Science Foundation of China [52072394, 21835007, 81802181]
- Shanghai Science and Technology Committee Rising-Star Program [19QA1410100]
- Shanghai International Cooperation Project [20490714200]
- Key Research Program of Frontier Sciences, Chinese Academy of Sciences [ZDBS-LY-SLH029]
- National Key Research and Development Program of China [2018YFC1106300]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20172026]
This study applied mild magnetic hyperthermia therapy to improve the healing of bone defects. The use of core-shell structured magnetic iron oxide nanoparticles in a hydrogel composite promoted osteogenesis and angiogenesis, demonstrating great potential for clinical applications.
Mild hyperthermia is greatly beneficial to the healing of bone defects; however, how to generat hyperthermia directly at the bone defect site remains an unsolved problem due to the poor thermal conversion capability of currently commercially available materials and the thickness of soft tissues. Herein, we applied mild magnetic hyperthermia therapy (MHT) to restore critical-sized bone defect using an Arg-Gly-Asp (RGD)-coated, core-shell structured magnetic iron oxide nanoparticle (MION; CoFe2O4@MnFe2O4) material to fabricate an optimized osteoinductive nanoparticles-hydrogel composite by embedding the nanoparticles in the agarose with a prominent magnetothermal effect. An alternating magnetic field with strong tissue penetration could evoke a mild MHT (41-42 degrees C) in the composites, which significantly promoted the osteogenic differentiation and biomineralization of pre-osteoblasts via a heat shock protein (HSP) 90-activated PI3K/Akt pathway. Simultaneously, the cobalt element in the CoFe2O4@MnFe2O4 upregulated the expression of the angiogenesis-related gene HIF-1 alpha, which was further promoted under mild heat stimulation. The dual effects notably facilitated the formation of new blood vessels at the lesion. This work demonstrates the great potential of MION-induced mild magnetothermal therapy for the efficient regeneration of critical-sized bone defects. (C) 2022 Elsevier Ltd. All rights reserved.
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