Calcium phosphate ceramics as molecular bone inducers
Calcium phosphate ceramics are widely used in the clinic as bone graft substitutes. Many types of ceramics are known, differing in both material chemistry and surface structure. In the past, we used porous calcium phosphate ceramics as a scaffold for autologous bone tissue engineering.
We shifted our focus because our colleagues at Progentix b.v. and the department of IBE discovered that ceramics can acquire osteo-inductive properties: they can trigger differentiation of stem cells into osteoblasts in vivo! A guiding design principle is that the ceramics are microporous.
Bone tissue (red stain) formed by human mesenchymal stem cells, seeded onto a porous calcium phosphate ceramic (black). Note the osteocytes embedded in the calcified matrix (from Siddappa et al.).
AT cBITE, we want to understand how microporous materials activate the osteogenic differentiation process. We use for example transcriptomic approaches to analyze the genomic expression profiles correlating to bone induction. It seems that calcium and phosphate ions strongly induce a set of osteogenic marker genes, but surface topography is an osteogenic signal in itself. We also discovered that osteo-induction in mice is very much dependent on the genetic background of the mice. We think that modern molecular genetic tools will help to reverse engineer the elegant process of material-induced bone induction.
Inducing bone formation by cAMP/PKA pathway activation: Siddappa et al., PNAS, 2008
A gene network for bone induction: Groen et al., Adv Mater, 2017
A method to engineer new bone using ceramic particles: Chatterjea et al., Tissue Eng Part A, 2013
A mouse model for ceramics induced bone induction: Barradas et al., Integr Biol (Camb), 2013
Check out the website of our former colleagues at Progentix about clinical use of osteoinductive ceramics.
See the website of Pamela Habibović’ IBE lab to learn more about the osteo-induction from a material engineering angle.