Total joint replacement (TJR) is widely applied as a promising treatment for the reconstruction of serious joint diseases but is usually characterized by critical loss of skeletal muscle attachment to metal joint prostheses, resulting in fibrous scar tissue formation and subsequent motor dysfunction. Tissue engineering technology may provide a potential strategy for skeletal muscle regeneration into metal joint prostheses. Here, a porous titanium (Ti) alloy scaffold coated with carbon nanotubes (CNTs) and mesoporous silica nanoparticles (MSNs) through electrophoretic deposition (EPD) was designed as a mechano-growth factor (MGF) carrier. This two-layered coating exhibits a nanostructured topology, excellent MGF loading, and prolonged release performance via covalent bonding to improve myoblast adhesion, proliferation and myogenic differentiation in porous Ti alloy scaffolds without cytotoxicity. The Akt/mTOR signaling pathway plays a key role in this process. Furthermore, in vivo studies show that the scaffold promotes the growth of muscle, rather than fibrotic tissue, into the porous Ti alloy structure and improves muscle-derived mechanical properties, the migration of satellite cells, and possibly immunomodulation. In summary, this nanomaterial-coated scaffold provides a practical biomaterial platform to regenerate periprosthetic muscle tissue and restore comparable motor function to that of the natural joint.