Evolution of gradient concept for the application of regenerative medicine

•The beginning of the first idea for gradient was looks like a small primitive prototype apparatus as a toy with limited number of researchers.•However, very recently the tremendous manufacturing technology as over ~100 kinds of fabricated methods have been introduced, developed, evolved and commercialized by much more laboratories.

It has been recognized that tissue engineering and regenerative medicine (TERM) offers the next generation technology for whole organ and tissue transplantation for diseased, failed or malfunctioned organs. Biomaterials might be the one of the important factors to apply the complete bio-organ using TERM techniques. Around 30 years ago, the primitive concept of “Gradient Surface” had been introduced to improve the biocompatibility for biomaterials. However, the gradient concept of surface property is changing now numerous kinds of physicochemical properties very recently. In this review, the importance of the concept of gradient, the historical evolution of experimental methodology for the manufacturing of gradient surface during last over ~30 years in my research group and finally perspective as enabling technologies for the TERM area are summarized.