The acute inflammatory response to copper(II)-doped biphasic calcium phosphates

Infection and inflammation are two key features to consider to avoid septic or aseptic loosening of bone-implanted biomaterials. In this context, various approaches to fine-tune the biomaterial's properties have been studied in order to modulate the crosstalk between immune and skeletal cells....

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Published in:Materials today bio 2023-12, Vol.23, p.100814-100814, Article 100814
Main Authors: Thoraval, L., Thiébault, E., Siboni, R., Moniot, A., Guillaume, C., Jacobs, A., Nedelec, J.-M., Renaudin, G., Descamps, S., Valfort, O., Gangloff, S.C., Braux, J., Marchat, D., Velard, F.
Format: Article
Language:English
Subjects:
Biomaterials
Chemical and Process Engineering
Cu-doped biphasic calcium phosphate
Cytokines
Engineering Sciences
Full Length
Inflammation
NETosis
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Summary:Infection and inflammation are two key features to consider to avoid septic or aseptic loosening of bone-implanted biomaterials. In this context, various approaches to fine-tune the biomaterial's properties have been studied in order to modulate the crosstalk between immune and skeletal cells. Cation-doping strategies for tuning of calcium phosphates properties has been evidenced as a promising way to control the biomaterial-induced inflammatory process, and thus improving their osteoimmunomodulatory properties. Copper(II) ions are recognized for their antibacterial potential, but the literature on their impact on particulate material-induced acute inflammation is scarce. We synthesized copper(II) ions-doped biphasic calcium phosphate (BCP), intended to exhibit osteoimmunomodulatory properties. We addressed in vitro, for the first time, the inflammatory response of human primary polymorphonuclear neutrophils (PMNs) to copper(II) ions-doped or undoped (BCP) powders, synthesized by an original and robust wet method, in the presence or absence of LPS as a costimulant to mimic an infectious environment. ELISA and zymography allowed us to evidence, in vitro, a specific increase in IL-8 and GRO-α secretion but not MIP-1β, TNF-α, or MMP-9, by PMNs. To assess in vivo relevance of these findings, we used a mouse air pouch model. Thanks to flow cytometry analysis, we highlighted an increased PMN recruitment with the copper(II) ions-doped samples compared to undoped samples. The immunomodulatory effect of copper(II) ions-doped BCP powders and the consequent induced moderate level of inflammation may promote bacterial clearance by PMNs in addition to the antimicrobial potential of the material. Copper(II) doping provides new insights into calcium phosphate (CaP)-based biomaterials for prosthesis coating or bone reconstruction by effectively modulating the inflammatory environment. [Display omitted] •Copper(II) ions doping potentiates neutrophil recruitment in vivo in a murine air pouch model.•Copper(II) ions doping maintains a moderate level of inflammation in addition to providing antibacterial potential.•Copper(II) ions doping does not induce an exaggerated proteolytic environment.•Copper(II) ions doping provides new insights into calcium phosphate (CaP)-based bone replacement and regeneration.•Copper(II) ions-doped biphasic calcium phosphate powder synthesis is achievable at an industrial GMP scale.
ISSN:2590-0064
2590-0064
DOI:10.1016/j.mtbio.2023.100814