Biological surface-modification of biomaterials for regenerative medicine
Ito, Yoshihiro
Japan

The success of nuclear transfer of mammalian cells and establishment of human embryonic stem cells in 90fs opened the regenerative medicine using stem cells. Regenerative medicine is expected to enable regeneration of organs which replace damaged organs. In the field of regenerative medicine or tissue engineering, there are three major factors including stem cells, the scaffold, and the signal growth factors to regulate cell functions. We attempted to combine the latter two factors. Recent progress in biological science has revealed many types of growth factor proteins. These signal proteins regulate various cell functions such as growth, differentiation, secretion, and apoptosis. It is well known that the biosignal protein interacts with the cognate receptor on the cell surface to form a complex, and that the complex aggregates on the cell surface before being internalized into the cell. The internalized complex is then decomposed in lysosomes. However, it was not known which process is necessary to transduce the signal to the cellular nucleus until two decades ago. If the events on the cell surface are sufficient for signal transduction, then biomaterials incorporating immobilized biosignal molecules could have the potential to regulate cellular functions. Therefore, growth factor proteins were immobilized on various materials to test this hypothesis. Here we report recent progress of immobilization of growth factors on materials. I n the field of biomaterials, regulation of cellular function has been almost exclusively limited to adhesion regulation. For enhancement of adhesion, extracellular matrices and adhesion proteins, and adhesion peptides have been employed. However, there have been a few limited studies for the regulation of higher level of cell functions including growth, differentiation, secretion, and apoptosis. We revealed that materials can regulate these biological phenomena by immobilization of biosignal molecules such as insulin, epidermal growth factor (EGF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), erythropoietin.
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