Unexpected hydrophilicity and bio-selectivity of fluorinated PEEK: enhancing bone regeneration through macrophage and BMSC cooperation

Implantation is the most common strategy for treating large segment bone defects, while current implants mainly focus on osteogenic activity and early immune responses, ignoring their anti-infective capacity and late-stage immune cooperation. Herein, a unique asymmetric fluorine-containing structure was successfully designed and constructed on a poly-ether-ether-ketone (PEEK) surface via a substitution reaction with fluorine gas. On the one hand, the unexpected hydrophilicity of fluorinated PEEK enhanced the adhesion of bone marrow stem cells (BMSCs) via upregulation of focal adhesion-related signaling pathways, and the fluorine-rich surface simultaneously constructed an early osteoimmune microenvironment, collectively facilitating the early osteogenic process. On the other hand, the fluorinated interface further inhibited inflammation in BMSCs during the late-stage of osteogenesis, and a unique bio-selectivity was observed during the full term of therapy. Similar bio-responses were also found in other fluorinated bio-interfaces which were generated through the direct fluorination of commonly used biomaterials. Our findings suggest that direct fluorination is an effective, substrate independent, and versatile strategy to reactivate and upgrade the bio-performance of implants, offering a promising approach for clinical bone regeneration therapies.