Macrophage polarization by plasma sprayed ceria coatings on titanium-based implants: Cerium valence state matters

Abstract With inflammation increasingly recognized as a key factor that influences fracture healing, the immune response is considered as a critical component in determining biomaterial-mediated osteogenesis. Here, the ceria coatings are applied to the titanium substrates via plasma spraying under different process gas compositions, forming A-III (low Ce4+/Ce3+ ratio) and B-IV (high Ce4+/Ce3+ ratio) coatings. Results of protein adsorption and conformation indicated that the exposed cell-binding sites of fibronectin and subsequent cell morphology were associated with the Ce valence states. The A-III and B-IV coatings clearly restricted and promoted the spreading of the adherent RAW264.7 macrophages, respectively. Cell morphology differences between the coatings correlated with a change in the percentage of RAW cells expressing M2 surface markers Cd206/163, together with expression of anti-inflammatory cytokines Il10/1ra, while there was no significant difference between them in the percentage of M1-type macrophages. Owing to its higher catalase-mimetic activity, the B-IV coating exerted stronger inhibitory effects on reactive oxygen species generation and Nfkb activity than either A-III coating or Ti substrate. Consistently, the lowest expression levels of Nfkb-regulated pro-inflammatory cytokines Il6 and Tnfa were found for the B-IV coating. The manipulation of cerium valence states could be a good strategy in the design of orthopedic/dental implant coatings with beneficial immune response.