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

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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.

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Acknowledgments

The authors would like to thank Amber Annettte Sawyer for training with Bioquant image analysis software.

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Authors and Affiliations

  1. Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore, 119260, Singapore

    Maria Ann Woodruff, Subha Narayan Rath, Evelyn Susanto & Dietmar W. Hutmacher

  2. Stem Cells and Tissue Repair Group, Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore

    Larisa M. Haupt, Victor Nurcombe & Simon M. Cool

  3. Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore

    Dietmar W. Hutmacher, Victor Nurcombe & Simon M. Cool

Authors
  1. Maria Ann Woodruff
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  2. Subha Narayan Rath
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  3. Evelyn Susanto
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  4. Larisa M. Haupt
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  5. Dietmar W. Hutmacher
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  6. Victor Nurcombe
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  7. Simon M. Cool
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Corresponding author

Correspondence to Simon M. Cool.

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Maria Ann Woodruff and Subha Narayan Rath contributed equally to this work.

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Woodruff, M.A., Rath, S.N., Susanto, E. et al. Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model. J Mol Hist 38, 425–433 (2007). https://doi.org/10.1007/s10735-007-9137-y

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  • DOI: https://doi.org/10.1007/s10735-007-9137-y

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