text: The underlying mechanisms that enable bioactive glasses to act as materials for bone repair have been investigated since the first work of Hench et al. at the University of Florida.  Early attention was paid to changes in the bioactive glass surface.  Five inorganic reaction stages are commonly thought to occur when a bioactive glass is immersed in a physiological environment:
  # Ion exchange in which modifier cations (mostly Na) in the glass exchange with hydronium ions in the external solution.
  # Hydrolysis in which Si-O-Si bridges are broken, forming Si-OH silanol groups, and the glass network is disrupted.
  # Condensation of silanols in which the disrupted glass network changes its morphology to form a gel-like surface layer, depleted in sodium and calcium ions.
  # Precipitation in which an amorphous calcium phosphate layer is deposited on the gel.
  # Mineralization in which the calcium phosphate layer gradually transforms into crystalline hydroxyapatite, that mimics the mineral phase naturally contained with vertebrate bones.
  Later, it was discovered that the morphology of the gel surface layer was a key component in determining the bioactive response.  This was supported by studies on bioactive glasses derived from sol-gel processing.  Such glasses could contain significantly higher concentrations of SiO than traditional melt-derived bioactive glasses and still maintain bioactivity (i.e., the ability to form a mineralized hydroxyapatite layer on the surface).  The inherent porosity of the sol-gel-derived material was cited as a possible explanation for why bioactivity was retained, and often enhanced with respect to the melt-derived glass.
  Subsequent advances in DNA microarray technology enabled an entirely new perspective on the mechanisms of bioactivity in bioactive glasses.  Previously, it was known that a complex interplay existed between bioactive glasses and the molecular biology of the implant host, but the available tools did not provide a sufficient quantity of information to develop a holistic picture.  Using DNA microarrays, researchers are now able to identify entire classes of  genes that are regulated by the dissolution products of bioactive glasses, resulting in the so-called "genetic theory" of bioactive glasses.  The first microarray studies on bioactive glasses demonstrated that genes associated with osteoblast growth and differentiation, maintenance of extracellular matrix, and promotion of cell-cell and cell-matrix adhesion were up-regulated by conditioned cell culture media containing the dissolution products of bioactive glass.