Implant materials to be implanted in vivo, particularly dental implant materials, are widely used as artificial teeth capable of replacing missing teeth to restore the masticatory function of some or all of the missing teeth. The success rate and long-term prognosis of implant treatment are influenced by the bone quantity and quality of the implant site in the patient, and depend on the stability of the implant. The stability of the implant can be divided into physical fixation that is obtained when the implant is brought into contact with the surrounding bone upon implant placement and biological fixation that results from the formation of new bone tissue around the implant and the occurrence of osseointegration in the surrounding bone after placement of the implant (Guideline for Evaluation of Zirconia Materials, the Korea Food & Drug Administration, 2011).
When an implant is placed in the alveolar bone of an adult patient, the stability of the implant is reduced while bone resorption for forming new bone in the existing bone occurs. However, while new bone is formed around the implant, the stability of the implant gradually increases again by osseointegration between the implant and the alveolar bone. However, in the case of elderly patients in whom it is difficult to ensure initial implant stability important for osseointegration, due to insufficient bone quantity or quality, early failure of the implant may occur, and if a load is applied to the implant having low initial stability, delayed osseointegration may be caused by micro-motion. Until now, to overcome such shortcomings, it has been attempted to increase initial implant stability by changing the length or diameter of the implant itself or treating the surface of the implant to increase the ability of the implant to adhere to osteocytes. However, it is still difficult to ensure initial implant stability after implant placement by such physical changes (Nakamura K et al., International Journal of Prosthodontics 23:299-309, 2010).
Thus, in the case of not only elderly patients having insufficient bone quality and quantity, but also general adult patients, it is essential to apply biological factors in order to promote initial osseointegration after implant placement and shorten the treatment period. Until now, a product obtained by chemically immobilizing a physiologically active substance on the surface of a dental implant has not yet been commercialized. However, in the case of apatite which is used as a synthetic material to increase bone quantity during implant placement, studies have been conducted on the use of apatite together with a physiologically active material such as extracellular matrix protein, tissue growth factor or bone morphogenetic protein. In addition, products such as GEM21S (containing PDGF), INFUSE (containing BMP-2) and the like, obtained by applying apatite together with a physiologically active substance or coating the surface of apatite with a physiologically active substance, have been developed. However, there are problems in that, after these products are implanted in vivo, the physiologically active substance is not securely fixed to the surface of the apatite material and is easily released from the surface of the apatite material so as to be degraded by exposure to systemic blood, and thus the physiological activity of the physiologically active substance can be reduced and the physiologically active substance can cause side effects in tissues other than the target tissue. For this reason, for tissue regeneration by an implant, it is required that a physiologically active substance be securely fixed to the surface of the implant biomaterial so that the effective activity thereof can be maintained over a long period of time (KR 10-1213355).
Accordingly, the present inventors have made extensive efforts to solve the above-described problems occurring in the prior art, and as a result, have identified a short peptide sequence having a strong binding affinity for the surface of an implant, and have found that the peptide easily binds to the surface of a zirconia implant and is maintained in a stable state, thereby completing the present invention.
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USPTO Backgrounds