In situ whisker reinforced multiphase bioceramic scaffolds with fluorine-activated osteogenesis

Enhancing both the mechanical strength and osteogenic activity of calcium phosphate (CaP) ceramics remains a significant challenge, particularly when approached from the intrinsic properties of the ceramic matrix. Inspired by whisker reinforcement, this study investigates the mechanism of in situ whisker generation within hydroxyapatite (HAp) bioceramics through a solid-state reaction of multiphase systems, resulting in a ≈200% increase in compressive strength. Meanwhile, the fluorine (F)-activated osteogenesis is explored. Theoretical analysis indicates that in situ whisker formation requires a high interfacial energy difference and rapid mass transfer, facilitated by specific additives that meet three criteria: melting point ≈1437 °C, density comparable to HAp, and a Ca/P ratio (with HAp) > 1.67. The HAp/CaSO₄/CaF₂ multiphase whisker bioceramics show outstanding mechanical and biological performance. Importantly, F-activation further enhances bone regeneration by improving cellular metabolism and energy production through mitochondrial regulation, specifically by promoting oxidative phosphorylation and the tricarboxylic acid cycle, increasing ATP synthesis, and thereby facilitating osteogenic differentiation. In vivo experiments validated the superior bone regeneration performance of F-containing bioceramics. This study elucidates the mechanism of in situ whisker formation and presents a DLP-compatible fabrication strategy that integrates fluorine-activated osteogenesis with whisker reinforcement in CaP bioceramics, offering new perspectives for developing high-performance bone regenerative materials.