Titanium Surface Synergy: Strontium Incorporation and Controlled Disorder Nanotopography Optimize Osteoinduction

Osteoporotic fractures and arthritis represent a major socioeconomic health burden. Fragility fracture fixation and joint replacement are often undertaken using titanium (Ti) or Ti alloy implants. Ideally these should induce bone formation and reduce osteoclast formation. Nanoscale topographies are potent inducers of osteogenesis, and strontium (Sr) has both osteogenic and antiosteoclastic effects. We incorporated strontium into a titanium surface with an osteogenic disordered nanoscale topography. The surface comprises 120 nm diameter, 100 nm deep pits in a near-square order with deliberate offset from the center pit position up to ±50 nm, providing a pattern with an average center–center pit spacing of 300 nm (called near-square 50, NSQ50). Several surfaces were assessed, including NSQ50 alone, strontium incorporated alone, and combined, compared with control surfaces. We assessed the surfaces using a human bone marrow stromal cell (BMSC)/ bone marrow hematopoietic cell (BHSC) coculture capable of osteogenesis and osteoclastogenesis. The samples eluted Sr over long-term culture, and uptake of Sr was better with eluted Sr than with Sr added to the culture media. The NSQ50 pattern in Ti was osteogenic, and addition of Sr elution increased osteogenesis further for both flat and NSQ50 samples. Interestingly, BMSCs on all Ti samples did not secrete the receptor activator of nuclear factor kappa-Β ligand (RANKL) or macrophage colony-stimulating factor (M-CSF) while secreting osteoprotegrin (OPG) at high levels. This meant that no osteoclast formation was observed on any Ti surface. Therefore, using Sr-incorporated nanotopographical imprinting, we generated highly osteogenic Ti surfaces that inhibited osteoclast formation.