Neoteric Semiembedded β-Tricalcium Phosphate Promotes Osteogenic Differentiation of Mesenchymal Stem Cells under Cyclic Stretch

β-Tricalcium phosphate (β-TCP) is a bioactive material for bone regeneration, but its brittleness limits its use as a standalone scaffold. Therefore, continuous efforts are necessary to effectively integrate β-TCP into polymers, facilitating a sturdy ion exchange for cell regulation. Herein, a novel semiembedded technique was utilized to anchor β-TCP nanoparticles onto the surface of the elastic polymer, followed by hydrophilic modification with the polymerization of dopamine. Cell adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) under static and dynamic uniaxial cyclic stretching conditions were investigated. The results showed that the new strategy was effective in promoting cell adhesion, proliferation, and osteogenic induction by the sustained release of Ca 2+ in the vicinity and creating a reasonable roughness. Specifically, released Ca 2+ from β-TCP could activate the calcium signaling pathway, which further upregulated calmodulin and calcium/calmodulin-dependent protein kinase II genes in MSCs. Meanwhile, the roughness of the membrane and the uniaxial cyclic stretching activated the PIEZO1 signaling pathway. Chemical and mechanical stimulation promotes osteogenic differentiation and increases the expression of related genes 2–8-fold. These findings demonstrated that the neoteric semiembedded structure was a promising strategy in controlling both chemical and mechanical factors of biomaterials for cell regulation.