Availableonlineatwww.sciencedirect.com D Biomaterials ELSEVIER Biomaterials 24(2003)2161-2175 www.elsevier.com/locate/biomaterials Novel bioactive materials with different mechanical properties Tadashi Kokubo*, Hyun-Min Kim, Masakazu Kawashita Department of Material Chemistry, Faculty of Engineering, Graduate School of Engineering, Kyoto Unicersity, Yoshida, Sakyo-k Kyoto 606-8501, Japan Received 29 October 2002: accepted 19 January 2003 Abstract Some ceramics, such as Bioglass, sintered hydroxyapatite, and glass-ceramic A-W, spontaneously bond to living bone. They are called bioactive materials and are already clinically used as important bone substitutes. However, compared with human cortical bone, they have lower fracture toughness and higher elastic moduli. Therefore, it is desirable to develop bioactive materials with improved mechanical properties. All the bioactive materials mentioned above form a bone -like apatite layer on their surfaces in the living body, and bond to bone through this apatite layer. The formation of bone-like apatite on artificial material is induced by functional groups, such as Si-OH, Ti-OH, Zr-OH, Nb-OH, Ta-OH, -COOH, and PO4H2. These groups have specific structures revealing negatively charge, and induce apatite formation via formations of an amorphous calcium compound, e. g, calcium silicate. calcium titanate, and amorphous calcium phosphate. These fundamental findings provide methods for preparing new bioactive materials with different mechanical properties. Tough bioactive materials can be prepared by the chemical treatment of metals and ceramics that have high fracture toughness, e.g., by the Naoh and heat treatments of titanium metal, titanium alloys, and tantalum metal, and by H3 PO4 treatment of tetragonal zirconia Soft bioactive materials can be synthesized by the sol-gel process, in which the bioactive silica or titania is polymerized with a flexible polymer, such as polydimethylsiloxane or polytetramethyloxide, at the molecular level to form an inorganic-organic nano-hybrid. The biomimetic process has been used to deposit nano-sized bone-like apatite on fine polymer fibers, which were textured into a three-dimensional knit framework. This strategy is expected to ultimately lead to bioactive composites that have a bone-like structure and, hence, bone-like mechanical properties. C 2003 Elsevier Science Ltd. All rights reserved Keywords: Bioactivity: Bone; Apatite: Simulated body fluid(SBF); Biomimetic process; Titanium: Hybrid; Apatite-polymer composite 1. Introduct do not damage healthy tissue, do not pose any viral or bacterial risk to patients, and can be supplied at any Bone disease is a serious health condition that directly time in any amount. However, artificial materials mpacts on the quality of life of sufferers, particularly implanted into bone defects are generally encapsulated among the aged. In most cases, the treatment of bone by a fibrous tissue, and become isolated from the defects requires a bone graft, and sometimes in extensive surrounding bone. Consequently, they do not adhere to amount. In the EU and the USA, bone grafts have used bone, and this has been a critical problem in their use in mainly autogenous and allogenic bones. However, bone repair. Since the early 1970s, this issue has been collecting autogenous bones damages healthy body, ly, overcome by using bioactive ceramics that sponta and the amount that can be collected is severely limited. neot The recipients of allogenic bones sometimes succumb to body y bond to and integrate with bone in the living viral and bacterial infections from the donors and, in Various types of bioactive ceramics have been addition, the amount of allogenic bone that can be given developed over the last three decades. Among these, is limited. As a result, there is an impetus for thethe main bioactive ceramics used clinically are: the development of artificial bone substitute materials that Bioglass in the Na20-Cao-SiOr-P2O5 system [1] sintered hydroxyapatite(HA)(CaIo(PO4)6(OH)2 [2, 3 482 Orresponding author. Tel:+81-75-753-5527: fax: +81-75-753. sintered B-tricalcium phosphate(TCP)(Ca3 (PO4)2 []. HA/TCP bi-phase ceramic [5, and glassceramic A-W E-mail address: kokubo@sung. kuic kyoto-u ac jp(T. Kokubo containing crystalline oxyfluoroapatite(Calo(PO4)(O, 0142-9612/03/Ssee front matter o 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0142-9612(03)0004-9Biomaterials 24 (2003) 2161–2175 Novel bioactive materials with different mechanical properties Tadashi Kokubo*, Hyun-Min Kim, Masakazu Kawashita Department of Material Chemistry, Faculty of Engineering, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan Received 29 October 2002; accepted 19 January 2003 Abstract Some ceramics, such as Bioglasss, sintered hydroxyapatite, and glass-ceramic A-W, spontaneously bond to living bone. They are called bioactive materials and are already clinically used as important bone substitutes. However, compared with human cortical bone, they have lower fracture toughness and higher elastic moduli. Therefore, it is desirable to develop bioactive materials with improved mechanical properties. All the bioactive materials mentioned above form a bone-like apatite layer on their surfaces in the living body, and bond to bone through this apatite layer. The formation of bone-like apatite on artificial material is induced by functional groups, such as Si–OH, Ti–OH, Zr–OH, Nb–OH, Ta–OH, –COOH, and PO4H2. These groups have specific structures revealing negatively charge, and induce apatite formation via formations of an amorphous calcium compound, e.g., calcium silicate, calcium titanate, and amorphous calcium phosphate. These fundamental findings provide methods for preparing new bioactive materials with different mechanical properties. Tough bioactive materials can be prepared by the chemical treatment of metals and ceramics that have high fracture toughness, e.g., by the NaOH and heat treatments of titanium metal, titanium alloys, and tantalum metal, and by H3PO4 treatment of tetragonal zirconia. Soft bioactive materials can be synthesized by the sol–gel process, in which the bioactive silica or titania is polymerized with a flexible polymer, such as polydimethylsiloxane or polytetramethyloxide, at the molecular level to form an inorganic–organic nano-hybrid. The biomimetic process has been used to deposit nano-sized bone-like apatite on fine polymer fibers, which were textured into a three-dimensional knit framework. This strategy is expected to ultimately lead to bioactive composites that have a bone-like structure and, hence, bone-like mechanical properties. r 2003 Elsevier Science Ltd. All rights reserved. Keywords: Bioactivity; Bone; Apatite; Simulated body fluid (SBF); Biomimetic process; Titanium; Hybrid; Apatite-polymer composite 1. Introduction Bone disease is a serious health condition that directly impacts on the quality of life of sufferers, particularly among the aged. In most cases, the treatment of bone defects requires a bone graft, and sometimes in extensive amount. In the EU and the USA, bone grafts have used mainly autogenous and allogenic bones. However, collecting autogenous bones damages healthy body, and the amount that can be collected is severely limited. The recipients of allogenic bones sometimes succumb to viral and bacterial infections from the donors and, in addition, the amount of allogenic bone that can be given is limited. As a result, there is an impetus for the development of artificial bone substitute materials that do not damage healthy tissue, do not pose any viral or bacterial risk to patients, and can be supplied at any time, in any amount. However, artificial materials implanted into bone defects are generally encapsulated by a fibrous tissue, and become isolated from the surrounding bone. Consequently, they do not adhere to bone, and this has been a critical problem in their use in bone repair. Since the early 1970s, this issue has been overcome by using bioactive ceramics that sponta￾neously bond to and integrate with bone in the living body. Various types of bioactive ceramics have been developed over the last three decades. Among these, the main bioactive ceramics used clinically are: the Bioglasss in the Na2O–CaO–SiO2–P2O5 system [1], sintered hydroxyapatite (HA) (Ca10(PO4)6(OH)2 [2,3], sintered b-tricalcium phosphate (TCP) (Ca3(PO4)2 [4], HA/TCP bi-phase ceramic [5], and glassceramic A-W containing crystalline oxyfluoroapatite (Ca10(PO4)6(O, *Corresponding author. Tel.: +81-75-753-5527; fax: +81-75-753- 4824. E-mail address: kokubo@sung7.kuic.kyoto-u.ac.jp (T. Kokubo). 0142-9612/03/$ - see front matter r 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0142-9612(03)00044-9