Biomimetic Intrafibrillar Mineralization of Hierarchically Structured Amyloid‐Like Fibrils

Abstract 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.