Effects of strontium-incorporated micro/nano rough titanium surfaces on osseointegration via modulating polarization of macrophages

Macrophages perform multiple functions in both inflammation and wound healing, and are one of the fore front cells during implant osseointegration that influence subsequent process. Essential trace element modification may effectively modulate titanium implant surface biological properties. In this work, strontium (Sr) incorporated micro/nano rough titanium surfaces (Sr-SLA) was fabricated by hydrothermal treatment, and immunoreaction of macrophages was further investigated. In vitro results revealed that Sr doping inhibited inflammatory response of macrophages, further attenuated the inhibitory effect on following bone marrow derived cells (BMSCs) osteogenic differentiation. The regulation of macrophages by Sr-SLA likely involved ERK signaling pathway. Consistently, the in vivo study showed that compared with titanium surface sand-blasted with large grit and double acid-etched (SLA) implants, Sr-SLA implants could enhance new bone formation accompanied with more alternatively activated M2 macrophages infiltration and less classically activated M1 macrophages infiltration. These results reveal the immunomodulatory ability of Sr-SLA of adjusting the functional status of macrophages through inhibiting M1 polarization while promoting M2 polarization.