Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis
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Zou, Yan-Pei
Hu, An-Nan
Wang, Ben
Li, Juan
Huang, Lei
Chen, Wei-Sin
Su, Di-Han
Xiao, Lan
Xiao, Yin
Ma, Yi-Qun
Li, Xi-Lei
Bo Jiang, Li-
Dong, Jian
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Abstract
Bone matrix has distinct architecture and biochemistry which present a barrier on synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, we prepared the biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) using a facile synthetic methodology. The ECM/RSF/MNP scaffold is hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers, mimicking the bone minimum unit morphology. The scaffold demonstrated saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the β-sheet crystalline domain of RSF and the chelated magnetic nanoparticles could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by approximately 20%. The results indicated that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promoted cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro and new bone formation in a critical-size femur defect rat model. RNA sequencing revealed that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+/calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition and external physical stimulation on intracellular Ca2+ homeostasis.
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Advanced Healthcare Materials
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This is the peer reviewed version of the following article: Liang, H-F; Zou, Y-P; Hu, A-N; Wang, B; Li, J; Huang, L; Chen, W-S; Su, D-H; Xiao, L; Xiao, Y; Ma, Y-Q; Li, X-L; Bo Jiang, L; Dong, J, Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis, Advanced Healthcare Materials, 2023, pp. 2301724, which has been published in final form at https://doi.org/10.1002/adhm.202301724. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
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Biochemistry and cell biology
Medical biotechnology
Biomedical engineering
bone-mimetic regenerative scaffold
calcium homeostasis
decellularized extracellular matrix
magnetic nanoparticle
regenerated silk fibroin
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Liang, H-F; Zou, Y-P; Hu, A-N; Wang, B; Li, J; Huang, L; Chen, W-S; Su, D-H; Xiao, L; Xiao, Y; Ma, Y-Q; Li, X-L; Bo Jiang, L; Dong, J, Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis, Advanced Healthcare Materials, 2023, pp. 2301724