Bone engineering by phosphorylated-pullulan and β-TCP composite

Tomohiro Takahata, Takumi Okihara, Yasuhiro Yoshida, Kumiko Yoshihara, Yasuyuki Shiozaki, Aki Yoshida, Kentarou Yamane, Noriyuki Watanabe, Masahide Yoshimura, Mariko Nakamura, Masao Irie, Bart Van Meerbeek, Masato Tanaka, Toshifumi Ozaki, Akihiro Matsukawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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.

Original languageEnglish
Article number065009
JournalBiomedical Materials (Bristol)
Issue number6
Publication statusPublished - Nov 20 2015


  • bone formation
  • phosphorylated-pullulan
  • β-TCP

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Biomedical Engineering


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