Local Collagen Fibril Orientation Guides Mineral Growth Direction and Morphology: Parallelism in Bone, Cartilage, Enthesis Fibrocartilage, Calcifying Tendon, and Dentin

Extracellular matrix mineralization is a complex process that starts at the atomic scale and cascades upward. The organic matrix forms first, and then mineralization ensues. Using an array of 2D and 3D X-ray and electron microscopy techniques, we have characterized the relationship between the 3D assembly of collagen fibrils (in terms of bundling and long-range coalignment) and mineral, with a specific focus on how the collagen architecture patterns mineralization in various biological tissues, including bone, cartilage, enthesis fibrocartilage, calcifying tendon and dentin─including ectopic calcification events. In the locally oriented type I collagen-rich matrix of lamellar bone, volumetric simulations of mineral growth resulted in an estimated growth rate of 1.67× along the long axis direction of collagen for prolate mineral aggregates (tesselles). A similar prolate shape was seen for the well-aligned collagen of calcifying fibrocartilage, with the collagen direction and preferred mineral growth direction diverging by ∼15°. In woven bone (ordered and disordered type I collagen), mineral growth is more isotropic, and in calcifying cartilage (disordered type II collagen), mineral foci grow in an equiaxed fashion, producing spherical aggregates of mineral. A stratified/layered structure was also found in the mineral foci of periosteal collar calcifying cartilage. In predentin, planar arrays of type I collagen shape the oblate morphology of calcospherites. Regardless of whether mineralization occurs orthotopically or ectopically, a clear parallelism exists in vivo between the local collagen fibril texture and the preferred direction of microscale mineral growth, expansion, and patterning.