Development of novel hydrogel based composites for bone tissue engineering applications.

Abstract

The process of tissue engineering involves replacing and assisting in the healing of damaged tissues. Specifically for bone tissue repair, a clinical demand has developed for alternative materials to replace the existing bone grafting treatments. To date, various materials have been proposed, synthesised and fabricated as potential replacements, but none have been successful. Due to the continued deficiencies of current commercially available biological bone grafts, the search for alternative substitutes has recently come to the forefront of tissue engineering. The primary objective of this thesis involved the synthesis, photopolymerisation and characterisation of novel hydrogels and hydrogel based composite scaffolds for bone regeneration. Poly(ethylene) glycol dimethacrylate (PEGDMA) was chosen as the main macromolecular monomer for the work described herein. The first stage of the work consisted of investigating the effect of varying the concentration and molecular weight of the macromolecular monomer PEGDMA on the properties of the resultant hydrogels. Results showed the mechanical properties were tunable and predictably altered by varying the pore size and crosslink density of the hydrogel. Additionally, biocompatibility studies on selected hydrogels revealed that cell viability was greater than 86% for all extraction concentrations. Further characterisation was carried out on polymer blends of PEGDMA and polypropylene glycol dimethacrylate (PPGDMA), since homopolymers are often insufficient in terms of mechanical strength. Following these studies, there was an attempt to develop hydrogels that mimic bone in terms of water content. This resulted in the use of a hydrophobic material, i.e. polypropylene glycol. Results revealed that the incorporation of PPG into the system decreases the mechanical strength of the hydrogels, which was observed for both the compression and rheological studies. The toxicological results showed that the aforementioned set of hydrogels was not suitable for implantation unless numerous time-consuming washing steps were performed. Following from this, the next stage of the research, synthesis of photopolymerisable maleic polyvinyl alcohol was conducted through a one step reaction between maleic anhydride and polyvinyl alcohol (PVA) in toluene sulfonic acid/formamide mixed solvent. Synthesis was confirmed by nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). NMR results showed the hydroxyl groups of PVA were acylated by maleic anhydride. Subsequent photopolymerisation of the maleic PVA hydrogels resulted in a weak material that dissolved easily. As a result, PEGDMA was incorporated into the system to improve the material’s strength. In the final body of work, mechanical and bioactive properties for novel hydrogel based composites were investigated. Bioactive glass, β-tricalcium phosphate and hydroxyapatite were incorporated at varying ratios. Compression tests and rheological studies revealed that each individual bioceramic improved the compressive strength for each of the hydrogel based composites compared to the control hydrogel. The increase in compressive strength was subject to the XIV concentration of bioceramic and the crosslinking between individual bioceramics and PEGDMA. Biomineralisation studies revealed that the control hydrogels did not exhibit bioactive properties, as shown by the absence of an apatite layer after being submerged in simulated body fluid. An apatite layer was formed on all hydrogel based composites where a bioceramic was incorporated. Drug release studies showed that the release of the drug varied depending on the concentration of the bioceramic as well as the molecular weight of the polymer and the drug. Antibacterial studies demonstrated the ability of the hydrogel based composites to control the release of incorporated antibiotics, which could potentially reduce the risk of osteomyelitis by enabling bacterial inhibition.