Spherulitic Crystal Growth Drives Mineral Deposition Patterns in Collagen‐Based Materials

Abstract The formation of the hard tissues that provide support and mobility to organisms is achieved through the interplay of inorganic crystals and an organic framework composed of collagen and a small percentage of non‐collagenous proteins. Despite their clinical relevance, the mechanisms governing mineralization of the extracellular matrix are still poorly understood. By using 3D electron tomography and high‐resolution electron microscopy imaging and spectroscopy, it has been demonstrated that mineralization proceeds through a spherulitic‐like crystal growth process. First, aggregates of disordered crystals form in the interfibrillar spaces, which lead to the mineralization of adjacent fibrils. Mineral propagates steadily through the inter‐ and intrafibrillar spaces of the collagen structure forming layered spherulites that grow to confluence. The structure of the collagen fibrils serves as a protein scaffold to guide the formation of a myriad of platelet‐shaped crystallites that make up each of these spherulites. At their periphery, nanosized unmineralized areas remain, leading to the formation of the characteristic lacy pattern observed in the transversal cross‐section of mature calcified tissues. This study provides fundamental insights into the bone formation process and represents a potential strategy for complex materials design.