Collagen mineralization pathway guided by multiscale structure of intermuscular bone in crucian carp

Bones have garnered significant attention for their lightweight and high-toughness properties. The building block of bone is mineralized collagen fibrils, which are hierarchically organized across multiple scales to confer excellent mechanical properties. However, exploring the mineralization process of bone remains challenging due to its complex structure, including both compact and spongy components, which complicate the analysis of mineral growth within collagen. To investigate collagen-guided mineral deposition, intermuscular bone is selected as a model system because of its relatively simple structure. Our study reveals that the intermuscular bone features a highly organized collagen matrix with aligned fibrils, and its nanoscale mineral-collagen architecture closely mimics that of human bone. Initially, mineral precursors infiltrate the outermost layer of intermuscular bone, forming a mineralized layer assembled by intrafibrillar mineralized collagen. As mineralization progressed, precursors gradually spread along the long axis of collagen fibrils, resulting in numerous rugby-shaped mineralized regions that were observed along with lengths of 2-4 μm and diameters of 0.7-1.2 μm. Ultimately, the structure, composition and mechanical properties of the remineralized intermuscular bone are comparable to those of the original bone. Our findings are valuable for understanding the bone mineralization process and provide insights into potential applications for bone defect repair.