Bioengineered osteoinductive systems for surgical applications

Shields, David (2020) Bioengineered osteoinductive systems for surgical applications. PhD thesis, University of Glasgow.

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Abstract

Despite significant improvements in surgical implant manufacturing there remains a clinically unmet need for implantable bone regenerating scaffolds. Current clinical solutions such as the use of pelvic autologous bone graft give rise to additional symptoms and are unpredictable. An engineered customisable osteoinductive coating has been developed within this research group, however the translatable aspects have not yet been explored. As an orthopaedic surgeon with a clinical interest in complex trauma and limb reconstruction, an invested interest in the practical aspects in the application of this technology is maintained.

In this work, an engineered osteoinductive coating consisting of poly (ethyl acrylate) with fibronectin and bone morphogenetic protein 2 (BMP-2) is evaluated as a potential coating for surgical implantation. Firstly, it was found that the use of ethylene oxide to sterilise the system (on a variety of base materials) could be employed without significant detriment to the fibronectin network, however BMP-2 was not resilient enough to the process to warrant addition prior to sterilisation. The use of decellularised bone chips commercially available as a transport medium for the osteoinductive coating was explored using an in vivo critical defect model which demonstrated evidence of mature bone formation with BMP-2. In vivo experiments were carried out in the University of Glasgow Veterinary Research Facility and performed under personal (n°I44130F69) and project license (n°70/8638) issued by the Home Office under the Animals (Scientific Procedures) ACT 1986. A fully synthetic transport medium by way of a polymer (poly caprolactone) scaffold was investigated with mechanical compression testing and in vitro cell biocompatibility. Scaffold materials were found to accommodate cell adhesion and differentiation. Despite changes in scaffold pore size, density and addition of hydroxy apatite as a composite filler, mechanical properties did not reach those of current commercial products, specifically poly (methyl methacrylate) bone cement.

The findings of this work demonstrate potential translatable aspects of this osteoinductive scaffold. However further rigorous in vivo assessment of retained osteoinductive function following sterilisation is required, followed by analysis of safety and efficacy. Further work on the improvement on mechanical properties of a bioresorbable polymer scaffold are warranted.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Bioengineering, osteoinductive, scaffolds, growth factors, fibronectin, BMP-2, ethylene oxide.
Subjects: Q Science > Q Science (General)
R Medicine > RD Surgery
T Technology > TA Engineering (General). Civil engineering (General)
Colleges/Schools: College of Science and Engineering > School of Engineering > Biomedical Engineering
Supervisor's Name: Salmeron-Sanchez, Professor Manuel and Dalby, Professor Matthew and Virginia, Dr. Llopis-Hernandez
Date of Award: 2020
Depositing User: Mr David Shields
Unique ID: glathesis:2020-79053
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 25 Feb 2020 09:46
Last Modified: 19 Mar 2020 11:12
Thesis DOI: 10.5525/gla.thesis.79053
URI: http://theses.gla.ac.uk/id/eprint/79053
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