Construction of Silver-Calcium Micro-Galvanic Cell on Titanium for Immunoregulation Osteogenesis.

Objective: This work aims to construct a functional titanium surface with spontaneous electrical stimulation for immune osteogenesis and antibacteria. Impact Statement: A silver-calcium micro-galvanic cell was engineered on the titanium implant surface to spontaneously generate microcurrents for osteoimmunomodulation and bacteria killing, which provides a promising strategy for the design of a multifunctional electroactive titanium implant. Introduction: Titanium-based implants are usually bioinert, which often leads to inflammation-induced loosening. Electrical stimulation has therapeutic potential; however, its dependence on external devices limits its clinical application. Therefore, designing an electroactive titanium surface with endogenous electrical stimulation capability is a promising strategy to overcome implant failure induced by inflammation. Methods: The silver-calcium micro-galvanic cell was constructed on titanium substrate surfaces by the ion implantation technique. RAW264.7 and MC3T3-E1 were used for cell culture studies with the material to evaluate immunomodulatory and osteogenic abilities of the implant. The expression levels of inflammatory genes and voltage-gated Ca(2+) channel-related genes were tested for investigating the mechanism of immunoregulation. The antibacterial properties of the modified titanium were assessed. Finally, its immunomodulatory effects in vivo were verified by a mouse subcutaneous inflammation model. Results: The silver-calcium micro-galvanic modified titanium surface generates microcurrents and releases Ca(2+), which induces macrophage polarization toward the M2 phenotype and promotes osteogenic differentiation via paracrine signaling, exhibiting excellent antibacterial activity. Conclusion: The silver-calcium micro-galvanic cell on titanium could regulate the immune response to promote bone repair and exhibit antibacterial capabilities through noninvasive electrical stimulation, providing a promising strategy for the design of multifunctional electroactive implant surfaces.