Modulation of the osteoconductive property and immune response of poly(ether ether ketone) by modification with calcium ions

Both bone-forming cells and immune cells have pivotal roles in bone tissue repair. In this work, we prepared a Ca-modified poly(ether ether ketone) (PEEK) to enhance the osteoconductivity but mitigate immune response of cells. To modify Ca ions onto a chemically inert PEEK, PEEK was first coated with poly(norepinephrine) followed by soaking in Ca(OH)₂ aqueous solution. Modification of Ca ions onto PEEK enhanced the proliferation and differentiation of MC3T3-E1 preosteoblast cells and human mesenchymal stem cells, but had no apparent effect on MLC-6 osteoclast-like cells. Naïve RAW264.7 macrophages cultured on pristine PEEK produced proinflammatory cytokines, but not on Ca-modified PEEK. Lipopolysaccharide-stimulated RAW264.7 macrophages on Ca-modified PEEK produced lower levels of proinflammatory cytokines but higher levels of anti-inflammatory cytokines compared with those on pristine PEEK. Lower levels of proinflammatory cytokines on Ca-modified PEEK were partially owing to higher interleukin-10 production mediated by Ca-activated pathways. Simple Ca modification of PEEK was shown to activate osteoblastic cell proliferation and differentiation, and shift macrophages towards an anti-inflammatory/wound healing type, which would be useful not only for bone tissue implants but also other implanted biomaterials.