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Title: pH-responsive hydrogel composites containing microgels : restoring intervertebral disc height through polymer composition
Author: Lally, Sarah Joanne
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2012
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This thesis presents a study into the use of microgels to restore degenerated intervertebral discs (IVDs). This was undertaken using a pH-triggered microgel which was able to form self-supporting gels through an increase in pH. The microgels were based on the poly(A/MAA/X) formulation, where MAA is methacrylic acid and A is the structural and X is the crosslinking monomer. The microgel particles were also used to construct composite poly(ethylene glycol) dimethacrylate (PEGD) hydrogels. The properties of the microgels and the composite hydrogels were then investigated. Microgel particles were synthesised based on poly(EA/MAA/BDD) (poly(ethyl acrylate/MAA/butanediol diacrylate). These were able to swell on increasing pH. Concentrated dispersions formed a gel with a high elastic modulus. The EA and BDD were replaced with related monomers and gave gels with different properties. Using monomers with high glass transition temperatures reduced the rate of swelling, and using monomers with similar reactivity ratios appeared to produce more uniformly crosslinked particles. It is proposed from the data presented that those with a large difference in reactivity ratio resulted in microgel particles with a change in crosslinking gradient through the radius of the particle. In some cases this produced microgels which appeared to fragment on increasing pH. The microgels investigated were based on poly(EA/MAA/X), (E-X) with BDD, EGD (ethylene glycol dimethacrylate) and PEGD. The EGD and PEGD microgels were shown to fragment with increasing pH. Poly(EA/MAA/PEGD) dispersions were able to form a gel at a pH below the pKa which appeared to be an electrostatically repulsive gel. Following this work, it became apparent that the E-BDD microgel was the most ideal of all the microgels with gels giving low values tanδ and frequency dependence of tanδ (tanδ = G"/G', where G" is the viscous modulus and G' is the elastic modulus). It also appeared to give physical gels with the highest elastic modulus. This microgel was therefore used for the composite gels. The poly(EA/MAA/BDD) microgel was then used to form covalently-linked composite hydrogels with PEGD of different molecular weights. PEGD with a molecular weight less than 550 formed a hydrogel-linked microgel, with interpenetrating polymer chains. These composites had high G' values and swelling ratios. Using PEGD with molecular weights higher than 550 produced microgel-filled hydrogels which had high values for G' and swelling ratios. Furthermore, due to osmotic deswelling of the microgel particles, the dispersions underwent a gel-to-fluid transition prior to being heated with initiator and crosslinked. This meant that some of the formulations were injectable. The mixture of high molecular weight PEGD and microgel was therefore combined with an accelerator which enabled gel formation and crosslinking at physiological temperature. Composites formed under physiological conditions were then tested for their ability to support biomechanically meaningful loads using degenerated IVDs. The discs were then compressed and the compressive strain to measured. The results showed that the composite was able to restore the mechanical modulus and height of the degenerated disc, showing favourable results for future research.
Supervisor: Saunders, Brian; Freemont, Anthony Sponsor: Not available
Qualification Name: Thesis (Ent.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available