Artificial juxtacrine stimulation for tissue engineering.

To endow biomaterials with the ability to regulate cell functions such as proliferation, differentiation, and apoptosis, growth factor proteins were covalently immobilized. The proteins were immobilized on various matrices using different chemical methods. It was shown that insulin and epidermal growth factor stimulated cellular functions even after immobilization. Pattern-immobilization of growth factor proteins clearly demonstrated the stimulation by immobilized proteins. In other words, this type of stimulation by non-diffusional growth factors enabled us to regulate tissue formation with artificial biomaterials. The stimulation was enhanced by coimmobilization with adhesion factors. These stimulations due to the immobilized growth factors may mimic juxtacrine stimulation of membrane-anchored growth factors such as heparin-binding epidermal growth factor, transforming growth factor-alpha, and tumor necrosis factor-alpha.