title: Bone engineering by phosphorylated-pullulan and β-TCP composite.
abstract: A multifunctional biomaterial with the capacity bond to hard tissues, such as bones and teeth, is a real need for medical and dental applications in tissue engineering and regenerative medicine. Recently, we created phosphorylated-pullulan (PPL), capable of binding to hydroxyapatite in bones and teeth. In the present study, we employed PPL as a novel biocompatible material for bone engineering. First, an in vitro evaluation of the mechanical properties of PPL demonstrated both PPL and PPL/β-TCP composites have higher shear bond strength than materials in current clinical use, including polymethylmethacrylate (PMMA) cement and α-tricalcium phosphate (TCP) cement, Biopex-R. Further, the compressive strength of PPL/β-TCP composite was significantly higher than Biopex-R. Next, in vivo osteoconductivity of PPL/β-TCP composite was investigated in a murine intramedular injection model. Bone formation was observed 5 weeks after injection of PPL/β-TCP composite, which was even more evident at 8 weeks; whereas, no bone formation was detected after injection of PPL alone. We then applied PPL/β-TCP composite to a rabbit ulnar bone defect model and observed bone formation comparable to that induced by Biopex-R. Implantation of PPL/β-TCP composite induced new bone formation at 4 weeks, which was remarkably evident at 8 weeks. In contrast, Biopex-R remained isolated from the surrounding bone at 8 weeks. In a pig vertebral bone defect model, defects treated with PPL/β-TCP composite were almost completely replaced by new bone; whereas, PPL alone failed to induce bone formation. Collectively, our results suggest PPL/β-TCP composite may be useful for bone engineering.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Takahata
authors.forename: Takumi
authors.initials: T
authors.lastname: Okihara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shiozaki
authors.forename: Aki
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamane
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Masahide
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Irie
authors.forename: Bart
authors.initials: B
authors.lastname: Van Meerbeek
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsukawa
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000008:administration & dosage* / Q000138:chemical synthesis*; D002130:Calcium Phosphates / Q000737:chemistry*; D019245:Compressive Strength; D005260:Female; D005936:Glucans / Q000737:chemistry*; D015552:Injections, Intralesional; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D058726:Nanoconjugates / Q000737:chemistry* / Q000648:ultrastructure; D010766:Phosphorylation; D011817:Rabbits; D033081:Shear Strength; D013314:Stress, Mechanical; D013718:Tensile Strength; D016896:Treatment Outcome; D014458:Ulna Fractures / Q000473:pathology / Q000628:therapy*
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D005936:Glucans; D058726:Nanoconjugates; C485817:beta-tricalcium phosphate; C009109:pullulan