Journal of Molecular Histology

, Volume 38, Issue 5, pp 425–433

Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

  • Maria Ann Woodruff
  • Subha Narayan Rath
  • Evelyn Susanto
  • Larisa M. Haupt
  • Dietmar W. Hutmacher
  • Victor Nurcombe
  • Simon M. Cool
Original Paper

DOI: 10.1007/s10735-007-9137-y

Cite this article as:
Woodruff, M.A., Rath, S.N., Susanto, E. et al. J Mol Hist (2007) 38: 425. doi:10.1007/s10735-007-9137-y

Abstract

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 μg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (μCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factor-based therapies.

Keywords

Glycosaminoglycans Bone regeneration Biomaterials CT scanning 

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Maria Ann Woodruff
    • 1
  • Subha Narayan Rath
    • 1
  • Evelyn Susanto
    • 1
  • Larisa M. Haupt
    • 2
  • Dietmar W. Hutmacher
    • 3
    • 1
  • Victor Nurcombe
    • 2
    • 3
  • Simon M. Cool
    • 2
    • 3
  1. 1.Division of Bioengineering, Faculty of EngineeringNational University of SingaporeSingaporeSingapore
  2. 2.Stem Cells and Tissue Repair GroupInstitute of Molecular and Cell BiologySingaporeSingapore
  3. 3.Department of Orthopaedic Surgery, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

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