Acta Medica Okayama 2045-2322 4 2014 Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy EN Masamitsu Oshima Kaoru Inoue Kei Nakajima Tetsuhiko Tachikawa Hiromichi Yamazaki Tomohide Isobe Ayaka Sugawara Miho Ogawa Chie Tanaka Masahiro Saito Shohei Kasugai Teruko Takano-Yamamoto Takashi Inoue Katsunari Tezuka Takuo Kuboki Akira Yamaguchi Takashi Tsuji Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy. No potential conflict of interest relevant to this article was reported.