Open Access Te Herenga Waka-Victoria University of Wellington
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Modified Heparins for Bone Repair

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posted on 2023-05-18, 22:03 authored by Liam Sargison

Bone repair is a multifaceted and complex biological process with a high rate of failure. This can be improved with the assistance of heparan sulfate (HS) that can complex with important growth factors, particularly bone morphogenetic protein 2 (BMP2) to enhance bone repair. Unfortunately, commercially available HS populations are inconsistent in structure, biological activity, availability and price. Given these challenges, an opportunity exists to generate HS-mimicking glycosaminoglycan populations from readily available commercial supplies of pharmaceutical-grade heparin that retain many of the biological properties of heparin yet lack its anticoagulant effects. Importantly, the modified populations would be consistent in structure and bioactivity, and cheaper to produce than comparable heparan sulfate materials. Thus, several chemical modifications of heparin were explored, including changes to degrees of sulfation, polymerisation, N-substitution and carboxyl reduction, to generate 21 glycosaminoglycan populations. These populations were screened for their ability to bind BMP2, enhance BMP2 thermal stability, improve BMP2-mediated alkaline phosphatase expression, and screened for reduced anticoagulant activity. The most promising candidate, 18f, was further compared with an HS population (HS3) that has established bone healing activity. This 18f population was screened for protein-binding affinity by surface plasmon resonance and found to bind with high affinity to eight relevant growth factors and support in vitro bone matrix mineralisation in osteogenic conditions. However, the activation of appropriate bone-inducing cell signalling pathways and the expression of key osteogenic genes was less conclusive. This study affirms that HS-mediated bone healing can be replicated using heparin-derived populations in vitro. Analysis of 18f and other generated populations offers support that protein-specific sequences within an HS population may exist. Further in vitro and in vivo analysis is warranted, as well as elucidation of the glycan sequence of 18f.


Copyright Date


Date of Award



Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Chemistry; Cell and Molecular Bioscience

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level


Degree Name

Doctor of Philosophy

Victoria University of Wellington Unit

Ferrier Research Institute

ANZSRC Socio-Economic Outcome code

240803 Human pharmaceutical treatments; 280103 Expanding knowledge in the biomedical and clinical sciences; 280105 Expanding knowledge in the chemical sciences; 209999 Other health not elsewhere classified

ANZSRC Type Of Activity code

4 Experimental research

Victoria University of Wellington Item Type

Awarded Doctoral Thesis



Victoria University of Wellington School

School of Chemical and Physical Sciences


Hinkley, Simon; Daines, Alison; Cool, Simon; Smith, Raymond Alexander Alfred

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