Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings

Abstract

Older adults suffer from weakened and delayed bone healing due to age-related alterations in bone cells and in the immune system. Given the interaction between the immune system and skeletal cells, therapies that address deficiencies in both the skeletal and the immune system are required to effectively treat bone injuries of older patients. The sequence of macrophage activation observed in healthy tissue repair involves a transition from a pro-inflammatory state followed by a pro-reparative state. In older patients, inflammation is slower to resolve and impedes healing. The goal of this study was to design a novel drug delivery system for temporal guidance of the polarization of macrophages using bone grafting materials. A biomimetic calcium phosphate coating (bCaP) physically and temporally separated the pro-inflammatory stimulus interferon-gamma (IFNγ) from the pro-reparative stimulus simvastatin (SIMV). Effective doses were identified using a human monocyte line (THP-1) and testing culminated with bone marrow macrophages obtained from old mice. Sequential M1-to-M2 activation was achieved with both cell types. These results suggest that this novel immunomodulatory drug delivery system holds potential for controlling macrophage activation in bones of older patients.

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

“…A biomimetic calcium phosphate (bCaP) coating layer was designed to cover and separated the pro-M2 molecule simvastatin (SIMV) from IFN-γ to delay the stimulation of pro-reparative state following a pro-inflammatory phenotype ( Fig. 3 D) [ 136 ]. The successive M1 to M2 activation on this dual drug delivery system was observed with both THP-1 and bone marrow macrophages ( Fig.…”

“…Reprinted with permission from Ref. [ 73 , 135 , 136 ], Copyright (2014) Elsevier, Copyright (2018) Wiley and Copyright (2018) Elsevier. …”

Macrophage in vitro Response on Hybrid Coatings Obtained by Matrix Assisted Pulsed Laser Evaporation

“…The results could be correlated with the ability of Lf to modulate the polarization of macrophages through its anti-inflammatory properties [82] and also with the hydrophilic character of the hybrid coating [14]. In addition, M1-to-M2 transition on hybrid coatings of THP-1 cells stimulated with LPS could also be explained by the interference of the hydroxyapatite component [99,100] and the polymeric coating, which might be involved in a controlled release of the anti-inflammatory component [58].…”

Dodecenylsuccinic anhydride modified collagen hydrogels loaded with simvastatin as skin wound dressings

“…For example, it has been reported that calcium and strontium ions on a nanostructure titanium surface can increase M2 macrophage phenotype (Lee, Kim, Jang, & Park, 2016) or hydroxyapatite granules activate some M1, but more M2 activation of THP-1 cells (Fernandes, Zhang, Magri, Renno, & Van Den Beucken, 2017). Another study reported that carbonated hydroxyapatite in the form of a coating rather than in granules was a potent M1 stimulator for THP-1 cells, and then transitioned to M2 via simvastatin delivery (Alhamdi et al, 2018). In the present studies, we demonstrated that DDSA-collagen gels and materials carrying simvastatin were modulators of an M2 profile for THP-1 cells.…”