Sequential activation of M1 and M2 phenotypes in macrophages by Mg degradation from Ti-Mg alloy for enhanced osteogenesis

Abstract

Background Even though the modulatory effects of Magnisum (Mg) and its alloys on bone-healing cells have been widely investigated during the last two decades, relatively limited attention has been paid on their inflammation-modulatory properties. Understanding the activation process of macrophages in response to the dynamic degradation process of Mg as well as the relationship between macrophage phenotypes and their osteogenic potential is critical for the design and development of advanced Mg-based or Mg-incorporated biomaterials. Methods In this work, a Ti-0.625 Mg (wt.%) alloy fabricated by mechanical alloying (MA) and subsequent spark plasma sintering (SPS) was employed as a material model to explore the inflammatory response and osteogenic performance in vitro and in vivo by taking pure Ti as the control. The data analysis was performed following Student’s t-test. Results The results revealed that the macrophages grown on the Ti-0.625 Mg alloy underwent sequential activation of M1 and M2 phenotypes during a culture period of 5 days. The initially increased environmental pH (~ 8.03) was responsible for the activation of M1 macrophages, while accumulated Mg2+ within cells contributed to the lateral M2 phenotype activation. Both M1 and M2 macrophages promoted osteoblast-like SaOS-2 cell maturation. In vivo experiment further showed the better anti-inflammatory response, regenerative potentiality and thinner fibrous tissue layer for the Ti-0.625 Mg alloy than pure Ti. Conclusion The results highlighted the roles of Mg degradation in the Ti-0.625 Mg alloy on the sequential activation of macrophage phenotypes and the importance of modulating M1-to-M2 transition in macrophage phenotypes for the design and development of inflammation-modulatory biomaterials.

Assessment of the regenerative potential of macro-porous chitosan-calcium simvastatin scaffolds on bone cells

“…17,18 This cell line has been used as a model of human osteoblasts for tissue engineering applications. 19,20 Therefore, pre-treatment with 0.1-1 μM SV for 1, 3, or 7 days was performed to simulate the effects of short-time SV release on human osteoblast cells. Similar to the literature, 9,15,[21][22][23] this study did not observe impairment in cell viability with the use of any of the evaluated doses or pretreatment times.…”

Quercetin-solid lipid nanoparticle-embedded hyaluronic acid functionalized hydrogel for immunomodulation to promote bone reconstruction

“…Recent advances in tissue engineering approach combined with the induction of macrophage polarization to drive bone reconstruction at the defect site is encouraging. The incorporation of biomaterials with anti-inflammatory effects into the defective wound surface promotes the polarization of macrophages to the M2 type during inflammation due to contact or foreign body reaction [ 18 ]. The multiple regulatory molecules and anti-inflammatory factors derived from the polarization process are critical enablers for directing a series of bone tissue reconstructions.…”

“…During bone regeneration, the inflammatory response phase initiates early and significantly influences the subsequent angiogenic and osteogenic differentiation responses [ 15 , 16 ]. Natural immune cells mediate the inflammatory response; macrophages are one of the first cells to be recruited to the implant surface and are essential for the regulation of the bone immune response [ 17 , 18 ].…”

“…Resting macrophages (M0) are mainly polarized into two phenotypes: M1 and M2 [ 19 , 20 ]. The M1 phenotype is mainly characterized by the production of pro-inflammatory cytokines, such as IL-1β and tumor necrosis factor-alpha (TNF-α) [ 18 , 21 , 22 ]. These pro-inflammatory signals play a role in stimulating osteoclast responses and directing osteogenic differentiation responses [ 23 ].…”

Potential effects of biomaterials on macrophage function and their signalling pathways

“…193 The regulation of macrophage polarization by biomaterials that respond to spatial and temporal changes in physiological and pathological conditions has the potential to enhance immunotherapeutic efficacy and tissue repair and regeneration. [194][195][196] Smart or stimulus-responsive materials have emerged as promising candidates for biomedical engineering. 197 The assessment of the comprehensive cellular and molecular interactions of smart or stimuli-responsive materials with immune cells, non-immune cells and ECM is a pivotal step in biomaterial design.…”