Research advances, challenges and outlooks of copper-containing scaffolds derived from 3D printing for tissue repair

Bone infection and vascularization remain severe challenges in bone scaffold implantation surgery. Copper-based biomaterials have demonstrated dual functional capabilities for addressing these issues. However, achieving spatially controlled copper (Cu) content and distribution to maximize therapeutic efficacy without inducing cytotoxicity is still challenging. 3D printing technology, with its unique advantages in spatial controllability and personalized structure fabrication, provides a robust platform for developing functional copper-loaded scaffolds. This review systematically summarizes the development of 3D-printed copper-loaded biomaterial scaffolds across multiple material systems. We describe how 3D printing enables precise modulation of Cu ion release kinetics and scaffold architecture through controlled material composition and printing parameters, optimizing mechanical and biological performance. Furthermore, significant bottlenecks hindering clinical translation, particularly copper ion initialburst release and mechanical anisotropy, are highlighted. Strategies for overcoming these challenges are discussed to advance clinical translation of personalized copper-functionalized scaffolds for tissue regeneration.