Bioactive Hierarchical Structures for Genetic Control of Bone Morphogenesis

For thirty years it has been known that certain compositions of Na 2 O-CaO-P 2 O 5 -SiO 2 glasses will form a mechanically strong, chemical bond to bone. These materials have become known as bioactive glasses and the process of bonding is called bioactive fixation. Bioactive glasses are widely used clinically in the repair of bone defects. Recent research at the Imperial College Tissue Engineering Centre has now established that there is a genetic control of the cellular response to bioactive materials. Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses. The gene expression occurs very rapidly, within two days, and includes enhanced expression of cell cycle regulators. The consequence is rapid differentiation of the osteoblasts into a mature phenotype and formation of large three-dimensional bone nodules within six days in vitro. These cell culture results correlate with extensive human clinical results using the same bioactive material. The new genetic theory of bioactive materials provides a scientific foundation for molecular design of new generation of resorbable bioactive materials for tissue engineering and in situ tissue regeneration and repair. Application of this theory to the synthesis of bioactive foams for tissue engineering of bone is described.