Self-organizing bioceramic granules with wave-dissipating architectures for bone void filling.

Granular bone substitutes readily adapt to irregular defects but lack initial stability, often resulting in granule migration and clinical complications. Inspired by the structural stability of wave-dissipating concrete blocks, which protect breakwaters from wave impact, we fabricated wave-dissipating bioceramic granules using digital light processing-based 3D printing and evaluated their potential for bone repair. Of six wave-dissipating designs, Tetrapod, Dolos, and Hexaleg were demonstrated to self-organize into the architectures featuring optimal intergranular space for bone ingrowth and minimized granule loss under dynamic conditions. For the repair of unhealed femoral defects, however, the Hexaleg implantation exhibited loose defect filling and impaired bone remodeling, despite an individual Hexaleg showing osteogenic differentiation potential in vitro attributed to its inherent macropores. In contrast, the Tetrapod and Dolos implantations achieved full and stable defect filling, supporting effective blood circulation around the defects, as well as high-quality new bone formation and host bone maintenance. These results suggest that the architecture self-organized by granule packing plays a dominant role in bone regeneration, outweighing the effects of individual granule characteristics. Overall, this work presents Tetrapod and Dolos as novel and promising bone void fillers that leverage the structural stability of wave-dissipating concepts while providing architectural cues for osteogenesis.