Bone engineering by phosphorylated-pullulan and β-TCP composite

Biomed Mater. 2015 Nov 20;10(6):065009. doi: 10.1088/1748-6041/10/6/065009.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness
  • Animals
  • Bone Regeneration
  • Bone Substitutes / administration & dosage*
  • Bone Substitutes / chemical synthesis*
  • Calcium Phosphates / chemistry*
  • Compressive Strength
  • Female
  • Glucans / chemistry*
  • Injections, Intralesional
  • Materials Testing
  • Mice
  • Mice, Inbred C57BL
  • Nanoconjugates / chemistry*
  • Nanoconjugates / ultrastructure
  • Phosphorylation
  • Rabbits
  • Shear Strength
  • Stress, Mechanical
  • Tensile Strength
  • Treatment Outcome
  • Ulna Fractures / pathology
  • Ulna Fractures / therapy*

Substances

  • Bone Substitutes
  • Calcium Phosphates
  • Glucans
  • Nanoconjugates
  • beta-tricalcium phosphate
  • pullulan