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.

Assessment of Optimal Conditions for Marine Invertebrate Cell-Mediated Mineralization of Organic Matrices

“…The XRD pattern surprisingly shows a mix of aragonite and calcite phases, even though the solution did not contain Mg ions (Supplementary Figure S1f). Interestingly, these rhombs were nearly always in the center of the raised patches of mineralized collagen (Supplementary Figure S2 and Graphical Abstract images), appearing to be caused by a "spherulitic" mineral propagation pattern analogous to that recently reported by Macías-Sánchez et al for mineralized collagenous tissues such as bone, dentin and turkey tendon [48]. Given the centralized rhomb seen in all of the raised patches, it appears the rhomb may serve as a collection site that accumulates the mineral precursor droplets.…”

Subcanalicular Nanochannel Volume Is Inversely Correlated With Calcium Content in Human Cortical Bone

“…(5,10) These characteristics of the LCN have been deduced in part from numerous electron microscopic, X-ray nanotomographic and confocal laser scanning microscopic, as well as other imaging techniques. (11)(12)(13)(14) Recent advances in three-dimensional (3D) imaging of biomineralized tissues have enabled visualization of fine ultrastructural features in mineralizing turkey leg tendon, (15,16) mouse bone and calcified cartilage, (17) and human bone (18,19) beyond the $100 nm length scales of the LCN. 3D focused ion beamscanning electron microscopy (FIB-SEM) studies in turkey leg tendon and mouse bone and cartilage have described the existence of a subcanalicular or nanochannel network that is much more extensive than the LCN and may provide additional and complementary pathways for mineral ion and/or mineral precursor transport.…”

A 3D cell-free bone model shows collagen mineralization is driven and controlled by the matrix

“…The mineralized collagen domains were present as intergrown 2-5 μm globular structures within the matrix, alike the mineral ellipsoids observed in many other studies. [8a, 29–30]…”

“…The mineralized collagen domains were present as intergrown 2-5 µm globular structures within the matrix, alike the mineral ellipsoids observed in many other studies. [8a, [29][30] Mineral development as function of matrix mineral interactions. After establishing that our model reconstructs the mineralized bone matrix in a biomimetic process that requires no activity of osteoblasts or other bone-specific cells, we set out to study the mineral infiltration and maturation as a result of matrix-mineral interactions during bone biomineralization.…”