The role of micro-vibration parameters in inflammatory responses of macrophages cultured on biphasic calcium phosphate ceramics and the resultant influence on osteogenic differentiation of mesenchymal stem cells

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2021-10, Vol.9 (38), p.83-813
• Main Authors: Wu, Jinjie, Tang, Yitao, Pu, Ximing, Wang, Menglu, Chen, Fuying, Chen, Xuening, Zhu, Xiangdong, Zhang, Xingdong
• Format: Article
• Language: English
• Subjects: Animals; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biomaterials; Biomedical materials; Bionics; Bone biomaterials; Bone marrow; Calcium phosphates; Cell Adhesion - drug effects; Cell differentiation; Cell Differentiation - drug effects; Cell Survival - drug effects; Ceramics; Ceramics - chemistry; Ceramics - pharmacology; Culture Media, Conditioned - pharmacology; Cytokines; Differentiation (biology); Gene expression; Gene Expression Regulation - drug effects; Hydroxyapatites - chemistry; IL-1β; Inflammation; Inflammatory response; Interleukin 1; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Macrophages; Macrophages - cytology; Macrophages - metabolism; Mechanical stimuli; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Optimization; Osteogenesis; Osteogenesis - drug effects; Paracrine signalling; Parameters; Phenotypes; RAW 264.7 Cells; Stem cells; Stimulation; Stimuli; Substitute bone; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vibration
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d1tb00898f

Although in vitro studies have shown that biomaterials and mechanical stimuli can mediate inflammatory responses or regulate osteogenesis of MSCs, the underlying behaviour of the inflammatory response of macrophages on biomaterials mediated by mechanical stimuli, which regulates osteogenesis, is relatively unknown. Thus, it is imperative to explore the role of bionic mechanical stimulation in the biomaterial-mediated inflammatory response of macrophages. In this study, we used osteoinductive biphasic calcium phosphate (BCP) ceramics as the model biomaterial and chose micro-vibration stimulation (MVs) with three variable parameters (frequency, magnitude, and time). Based on orthogonal experiments, nine combinations of MVs parameters were generated, and their effects on the BCP-mediated macrophage inflammatory response were investigated. MVs significantly affected the gene expression and cytokine secretion of macrophages grown on BCP ceramics and further influenced the behaviour of bone marrow mesenchymal stem cells (BMMSCs) in a paracrine manner. Moreover, frequency seemed to be the most dominant factor (compared with magnitude and time) in regulating the inflammatory response of macrophages. The optimal combination of MVs parameters (frequency 10 Hz, magnitude 0.45 g, and time 60 min) could induce a healing-associated M2 phenotype, as evidenced by the downregulated pro-inflammatory gene ( Il-1β , and Tnf-α ) expression, the upregulated anti-inflammatory gene ( Il10 ) expression, and the inhibited pro-inflammatory cytokine (Il-1β and Tnf-α) secretion of macrophages grown on BCP ceramics, and its conditioned medium (CM) could further promote osteogenic differentiation of BMMSCs. These findings provide valuable insights into the mechanical stimulus-mediated macrophage inflammatory response and osteogenesis in the presence of osteoinductive BCP ceramics and allow accurate evaluation of the biological performance of biomaterials in vitro , in order to optimize bone substitute materials to achieve the desired clinical performance. Micro-vibration stimulation (MVs) plays a critical role in regulating the inflammatory responses of macrophages to BCP ceramics and further inducing the osteogenic differentiation of BMMSCs in a paracrine manner.