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Materials

Bony Variations

Cell type affects characteristics of engineered bone

by Celia Henry Arnaud
August 3, 2009 | A version of this story appeared in Volume 87, Issue 31

CULTURE DIFFERENCES
TEM images of bone nodules from embryonic stem cells (left) and osteoblasts (right) show that the materials are quite dissimilar.
Credit: Nat. Mater.

Not all engineered bone is created equal, a new study finds.

Molly M. Stevens of Imperial College London and coworkers have compared the "bone nodules" formed in cultures of osteoblasts (a type of bone cell), embryonic stem cells, and adult stem cells from bone marrow (Nat. Mater., DOI: 10.1038/nmat2505).

All three types of cells are being explored to generate new bone, Stevens says. "We find that the bone that's made from these different sources of cells ends up being quite different."

Native bone is composed primarily of hydroxyapatite—Ca10(PO4)6(OH)2—deposited on an extracellular matrix of the protein type I collagen. Natural bone forms three distinct mineral environments that can be distinguished by the position and shape of the phosphate bands in Raman spectra.

In Stevens' team's experiments, all three cultures form nodules with calcium-to-phosphorus ratios similar to those found in native bone, but closer inspection reveals decided differences. Multivariate factor analysis of Raman spectra shows that the mineral environments within bone nodules formed by osteoblast and adult stem cell cultures are more complex than those produced by embryonic stem cells.

Other tests show that the nodules from embryonic stem cells are less stiff than nodules from osteoblasts and adult stem cells. In addition, the embryonic stem cells form fibrous structures that don't associate with collagen fibrils the way bone normally does. The bone nodules formed by embryonic stem cells are more like the highly crystalline mineral found in older bone than that found in normal bone.

This work sheds light on the "inherent mysteries of the calcified matrix of bone and underscores the need to understand and characterize fundamental biological design before we tissue-engineering scientists move forward too quickly," says Jeffrey O. Hollinger, director of the Bone Tissue Engineering Center at Carnegie Mellon University.

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