Biomimetic Intrafibrillar Mineralization of Hierarchically Structured Amyloid‐Like Fibrils

Intrafibrillar mineralization is essential not only as a fundamental process in forming biological hard tissues but also as a foundation for developing advanced composite fibril-based materials for innovative applications. Traditionally, only natural collagen fibrils have been shown to enable intrafibrillar mineralization, presenting a challenge in designing ordered hierarchical fibrils from common protein aggregation that exhibit similar high intrafibrillar mineralization activity. In this study, a mechanically directed two-step transformation method is developed that converts phase-transitioned protein nanofilms into crystalline, hierarchical amyloid-like fibrils with multilayer structures, which effectively control the growth and lateral organization of hydroxyapatite within adaptive gaps. The resulting mineralized HSAF achieves a hardness of 0.616 ± 0.007 GPa and a modulus of 19.06 ± 3.54 GPa-properties closely resembling native hard tissues-and exhibits exceptionally high bioactivity in promoting both native bone tissue growth and further intrafibrillar mineralization, achieving 76.9% repair in a mice cranial defect model after 8 weeks and outperforming other regenerative materials. This remarkable performance, stemming from the unique structure and composition of the fibers, positions HSAF as a promising candidate for biomedical and engineering applications. These findings advance the understanding of biomineralization mechanisms and establish a foundation for developing high-bioactivity materials for hard tissue regeneration.