Early Bone Growth Imaged

The earliest stages of bone formation have been imaged for the first time in high resolution. The work provides an improved understanding of bone, tooth and shell formation, which has applications in bone-replacement materials and nanotechnology.

Researchers at Eindhoven University of Technology (TU/e) used the cryoTitan advanced electron microscope to make three-dimensional images of the nanoparticles that are at the heart of the biomineralization process.

Biomineralization is the formation of inorganic materials in a biological environment, as it is found in bones, teeth and shells. In this process, the formation of the mineral is controlled with great precision by specialized organic biomolecules such as sugars and proteins. Although the underlying mechanisms have already been studied for a long time, the process is still not fully understood.

Shown is a 3-D electron microscopy image of the calcium carbonate crystals that grow to the organic surface. The flat part of the crystals is in contact with the organic layer. (The width of the crystals is ~400 nm) Image: Nico Sommerdijk.

Led by Dr. Nico Sommerdijk, the researchers imaged small clusters with a cross section of 0.7 nm in a solution of calcium carbonate (the basic material of which shells are made). They showed for the first time that these clusters, each consisting of only about 10 ions, are the beginning of the growth process through which the crystalline biomineral ultimately is formed.

Through the very high resolution available with FEI Co.’s cryoTitan, the researchers made 3-D images of very rapidly frozen samples. These showed how the clusters in the solution nucleate into larger, unstructured nanoparticles with an average diameter of around 30 nm (a video of the process can be seen here).

An organic surface applied by the researchers ensures that the nanoparticles can grow into larger particles, in which crystalline regions can later form by ordering of the ions.

The TU/e researchers also demonstrated a second function of the organic layer: It controls with great precision the direction in which the mineral can grow into a fully fledged biomineral. They now hope to show that the mechanism they have identified also applies to the formation of other crystalline biominerals, and perhaps even to other, inorganic materials.

This is important for research into bone growth and bone-replacement materials. It also could be used in nanotechnology, to allow the growth of nanoparticles to be controlled in the same way as seems to be the case in nature: through subtle interactions between organic and inorganic materials.

The findings are featured in the March 13 cover story of Science magazine.

For more information, visit: w3.tue.nl/en/