Strontium-Incorporated Carbon Nitride Nanosheets Modulate Intracellular Tension for Reinforced Bone Regeneration

Strontium-containing agents have been demonstrated to elicit both bone anabolic and antiosteoporotic effects, showing great potential for the treatment of bone loss. However, an increased incidence of strontium-induced side effects restricts their clinical applications. Herein, oxidized carbon nitride nanosheets (CN) are delicately used to incorporate Sr²⁺ for the first time to achieve high osteogenic efficacy. The lamellar structure and enriched nitrogen species of CN provide them with a high surface area-to-volume ratio and abundant anchoring sites for Sr²⁺ incorporation. Importantly, Sr²⁺-incorporated CN (CNS) could synergistically promote osteoblast differentiation and bone regeneration at a single, very low Sr²⁺ dose. Mechanically, CNS could activate the FAK/RhoA signaling pathway to modulate the intracellular tension that stimulates osteoblasts differentiation. The present study will provide a new paradigm to enhance the efficacy of osteogenic metal ions by using lamellar nanocarriers.