Modulating macrophage polarization with divalent cations in nanostructured titanium implant surfaces

Abstract

Nanoscale topographical modification and surface chemistry alteration using bioactive ions are centrally important processes in the current design of the surface of titanium (Ti) bone implants with enhanced bone healing capacity. Macrophages play a central role in the early tissue healing stage and their activity in response to the implant surface is known to affect the subsequent healing outcome. Thus, the positive modulation of macrophage phenotype polarization (i.e. towards the regenerative M2 rather than the inflammatory M1 phenotype) with a modified surface is essential for the osteogenesis funtion of Ti bone implants. However, relatively few advances have been made in terms of modulating the macrophage-centered early healing capacity in the surface design of Ti bone implants for the two important surface properties of nanotopography and and bioactive ion chemistry. We investigated whether surface bioactive ion modification exerts a definite beneficial effect on inducing regenerative M2 macrophage polarization when combined with the surface nanotopography of Ti. Our results indicate that nanoscale topographical modification and surface bioactive ion chemistry can positively modulate the macrophage phenotype in a Ti implant surface. To the best of our knowledge, this is the first demonstration that chemical surface modification using divalent cations (Ca and Sr) dramatically induces the regenerative M2 macrophage phenotype of J774.A1 cells in nanostructured Ti surfaces. In this study, divalent cation chemistry regulated the cell shape of adherent macrophages and markedly up-regulated M2 macrophage phenotype expression when combined with the nanostructured Ti surface. These results provide insight into the surface engineering of future Ti bone implants that are harmonized between the macrophage-governed early wound healing process and subsequent mesenchymal stem cell-centered osteogenesis function.

The response of human osteoblasts, epithelial cells, fibroblasts, macrophages and oral bacteria to nanostructured titanium surfaces: a systematic study

“…[10][11][12] Although rapid physiological resolution of inflammation is conducive to tissue healing, continued chronic inflammation would result in the hyperplasia of fibrotic scar tissue, ultimately leading to implant failure. 13,14 Therefore, it would also be beneficial for early tissue healing and implant success to control the inflammatory process through macrophage polarization.…”

The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research

“…In addition, M1 activated macrophages could be re-educated into the M2 phenotype, and vice versa, by further changes in the stimuli. This process is referred to as macrophage reprogramming or repolarization [33,34]. …”

“…TiO 2 NPs are of significant concern in the field of implants because titanium metal resists corrosion from the body. The expression of M2 subtype markers (Arg1, MR, and CD163) was markedly increased on the surface of bioactive ion Ca and Sr-modified nanostructured Ti implants [33]. Further studies showed that surface bioactive ion modification on the nanotopography of Ti implants plays an important role in inducing M2 macrophage polarization by modulating the shape and spread of adherent macrophages.…”

“…Further studies showed that surface bioactive ion modification on the nanotopography of Ti implants plays an important role in inducing M2 macrophage polarization by modulating the shape and spread of adherent macrophages. Modulating the M2 polarization by surface nanotopography and chemistry of nanostructured Ti implants provides insight into the basis for the rational design of implants, which orchestrate the early wound healing process and osteogenesis [33]. …”

Manufacturing of metallic micro-components using hybrid soft lithography and micro-electrical discharge machining

“…This is because metals exhibit high strength, which minimises the possibility of experiencing major failures. Therefore, they have been the main choice of hermetic seals of large biomedical implants such as pacemakers [9][10][11].…”