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Recent development of biomedical engineering including biomaterials and drug delivery system (DDS) as well as basic biology and medicine has enabled cells to induce regeneration repairing of defective tissues as well as substitute the biological functions of damaged organs. For successful tissue regeneration, it is undoubtedly indispensable to give cells a local environment which allows cells to efficiently promote their proliferation and differentiation and consequently induce cell-based tissue regeneration. Tissue engineering is one of the biomedical forms to create this regeneration environment of cells. The tissue and organ repairing based on their regeneration induction has been realized by combining cells with the tissue engineering technology or methodology in a surgical or internally medical manner. This paper overviews the present status and future direction of tissue engineering for regenerative inductive therapy, briefly explaining the key technology of tissue engineering, especially DDS of growth factor and gene.

This paper investigates the controlled release of hepatocyte growth factor (HGF) by biodegradable gelatin hydrogels and their HGF-induced angiogenic effect. Hydrogels of different degradabilities were prepared through chemical crosslinking gelatin with varied amounts of glutaraldehyde. When the gelatin hydrogels were radioiodinated and subcutaneously implanted into the back of mice, the remaining radioactivity of the hydrogels decreased with time. However, the remaining period became longer when the concentration of glutaraldehyde used for hydrogel preparation increased. Following implantation of gelatin hydrogels incorporating 125I-labeled HGF, the HGF radioactivity retained in the mouse subcutis for longer time periods as the glutaraldehyde concentration becomes higher. The time profile of HGF remaining in every gelatin hydrogel was in good accordance with that of hydrogel degradation, indicating HGF release as a result of hydrogel biodegradation. The gelatin hydrogel incorporating HGF histologically induced angiogenic change around the implanted hydrogel. Gelatin hydrogels incorporating 5 and 10 microg HGF significantly enhanced the number of capillaries newly formed around the implanted site. This was in marked contrast to free HGF of same dose form and HGF-free, empty gelatin hydrogel. The gelatin hydrogel incorporating HGF induced VEGF around the implanted site. In vitro bioassay revealed that HGF molecules interacting with gelatin, still exhibited the biological activity. The interacted HGF would be released from gelatin hydrogels only when they were degraded to generate water-soluble gelatin fragments. It is possible that the HGF associating gelatin fragments of bioactivating, results in induced angiogenic effect.