ABSTRACT

Tissue engineering has increasingly attracted interest as a promising new technology to assist tissue regeneration at body defects as well as biological functions of damaged or injured organs. There are three factors necessary for tissue engineering: growth factors, cells, and materials for scaffolding. Since among them is growth factor of protein or glycoprotein, which is susceptible to proteolysis and denaturation, if the growth factor is administered in solution form into the body, one cannot always expect the biological function. Therefore, it is of prime necessity to develop dosage forms for in vivo prolongation of the biological activity. One possible way is to incorporate a growth factor into an appropriate matrix for achieving controlled release of the factor at the site of action over a long time period. Numerous studies have been performed on protein release by taking advantage of polymer matrices (1-5), but there is a problem before us in the protein release technology, i.e., loss in the biological activity of protein released. It has been demonstrated that this activity loss mainly results from protein denaturation and deactiva­ tion during a formulation process with a polymer matrix. When exposed to harsh environmen­ tal changes, such as heating and exposure to sonication and organic solvents, protein is gener­ ally denatured, losing its biological activity (6 - 8 ). Therefore, it is required to contrive a new formulation method for growth factor release under mild conditions to minimize protein deac­ tivation. From this viewpoint, hydrogel is a preferable candidate for a release matrix because of its biosafety and inertness toward protein (9). However, it should be noted that the period of protein release from hydrogels is mostly as short as a day because of their diffusion-controlled characteristics (1,2,9,10).