Repair of Infected Bone Defect with Clindamycin-Tetrahedral DNA Nanostructure Complex-loaded 3D Bioprinted Hybrid Scaffold

• Tetrahedral DNA nanostructure provides an effective drug delivery vehicle. • We constructed a 3D-bioprinted scaffold loaded with TDN-clindamycin complex. • The novel scaffold was biocompatible, with osteogenic and antimicrobial properties. • The scaffold significantly improved repair in rat model of infected bone defect. Infection of bone defects is a common clinical problem that negatively impacts bone repair and may result in the development of antibiotic resistance due to the long-term use of antibiotics. To the best of our knowledge, integrating tetrahedral DNA nanostructure (TDN) drug delivery with 3D bioprinting has not been reported to treat infected bone defects. However, numerous studies have focused on effectively controlling infected bone defects and achieving functional reconstruction. In this study, TDN was proposed as a drug delivery vehicle to enhance cell penetration and the antibacterial properties of clindamycin (CLI), a common antibiotic used to treat osteomyelitis. A 3D hybrid scaffold loaded with TDN-CLI complexes was constructed using bioprinting technology. Its structure and biological properties were characterized, and the scaffold was further applied to treat methicillin-resistant Staphylococcus aureus (MRSA) infection in a rat model of bone defect. The results demonstrated that the TDN-CLI-loaded 3D bioprinted hybrid scaffold possessed excellent biocompatibility, outstanding osteogenic and antimicrobial activity, and significantly improved the repair of infected bone defects in the rat model. The TDN-CLI-loaded hybrid scaffold developed in the current study has broad application prospects for treating infected bone defects.