Advances in 3D Printed Bone Implants: Smart Responsive Antibacterial Strategies and AI-Driven Design

For critical-sized bone defects, bioactive implants are indispensable. Although advanced three-dimensional (3D) printing technology enables the precise manufacturing of customized bone scaffolds, implant-associated infections (IAIs) remain a significant clinical challenge. Moreover, traditional passive antibacterial coatings often face problems such as uncontrolled release of antibacterial agents and insufficient long-term antibacterial efficacy. This review elaborates on the transformation of antibacterial strategies in the field of bone tissue engineering (BTE) from "passive" to "smart responsive" modes. We summarize the endogenous (such as pH, temperature, reactive oxygen species (ROS), and enzyme) and exogenous (such as light, microwave, and ultrasound) response systems. Notably, the ultrasound-driven strategy is highly emphasized due to its outstanding deep tissue penetrability and dual functional characteristics: it can not only eliminate stubborn biofilms through the sonodynamic effect by generating ROS, but also promote osteogenesis through the piezoelectric effect. Additionally, we also discuss the recent progress of artificial intelligence (AI) in the field of bone scaffold manufacturing. AI-driven algorithms help to rapidly optimize complex scaffold structures and accurately predict their mechanical properties, thereby effectively avoiding the inefficiencies brought about by the traditional "trial and error" method. In conclusion, combining AI-assisted manufacturing technology with smart responsive antibacterial strategies opens up a highly promising frontier field for the development of personalized and infection-free bone implants.