title: Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model.
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 microg 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 (microCT) 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.
authors.affiliation: Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore. biewma@nus.edu.sg
authors.forename: Maria Ann
authors.initials: MA
authors.lastname: Woodruff
authors.forename: Subha Narayan
authors.initials: SN
authors.lastname: Rath
authors.forename: Evelyn
authors.initials: E
authors.lastname: Susanto
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.forename: Victor
authors.initials: V
authors.lastname: Nurcombe
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cool
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D010012:Osteogenesis / Q000502:physiology*; D010294:Parietal Bone / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D014945:Wound Healing
chemical_list: D000469:Alkaline Phosphatase; D050659:Core Binding Factor Alpha 1 Subunit; D015718:Fibrin Tissue Adhesive; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; C493717:Runx2 protein, rat