Ultrasound-responsive MoS2@pCu-MOF heterojunction scaffold: Enhancing bacterial membrane permeability, exhibiting efficient antibacterial activity and facilitating bone regeneration

Abstract

Phosphate-based Cu-MOF (pCu-MOF), a bioactive material with copper ions as framework centers and phosphate as the skeleton, shows chemodynamic antibacterial properties and bone regeneration potential via PO₄³ ⁻ release. However, its chemodynamic therapy (CDT) relies too much on cellular microenvironment's hydrogen peroxide (H₂O₂) level, and low-concentration reactive oxygen species (ROS) can't penetrate the bacterial membrane well, limiting antibacterial efficiency. To solve this, we created MoS₂@pCu-MOF type-II heterojunction nanocomposites to boost bacterial membrane permeability, effectively eliminating bacteria and promoting bone regeneration. Sonodynamic therapy (SDT) increases membrane permeability, allowing ROS to penetrate and disrupt bacteria. The type-II heterojunction, with SDT ability, generates hydroxyl radicals (·OH) and singlet oxygen (¹O₂) independently of H₂O₂ level by promoting electron-hole pair separation, achieving high antibacterial activity. Also, heterojunction-induced microcurrents under SDT synergize with PO₄³ ⁻ to stimulate osteogenesis. We incorporated MoS₂@pCu-MOF nanocomposites into a poly-l-lactic acid (PLLA) scaffold via selective laser sintering. Under ultrasonic stimulation, bacterial membrane permeability increases. Separated charge carriers bind to active sites of the MoS₂@pCu-MOF heterojunction scaffold to generate ·OH and ¹O₂, enabling high antibacterial efficiency without relying on CDT. Electrochemical experiments showed improved electron-hole separation efficiency of the heterojunction scaffold. PO₄³ ⁻ release and ultrasound-induced microcurrents promoted bone regeneration. Results indicated that the inhibition rates of Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli) reached 99 % and 98.5 %, respectively. Notably, ultrasound-induced microcurrents enhanced the scaffold's osteogenic capacity by 36 % at the late osteogenesis stage on the basis of ion stimulation and facilitated the expression of osteogenic factors like Runx-2, Wnt-10b, and BMP-2. These findings suggest MoS₂@pCu-MOF heterojunction scaffolds can achieve effective SDT/CDT dual-mode antibacterial activity and promote bone regeneration via ionic/sonoelectric dual-mode.