Development of Amphiphilic Biohybrid Hydrogels for Cell Delivery to the Nucleus Pulposus
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Authors
Brissenden, Amanda
Date
Type
thesis
Language
eng
Keyword
Biomaterials , Hydrogel
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Abstract
Restoration of the nucleus pulposus (NP) by cell therapy has emerged as a promising treatment for intervertebral disc degeneration. Hydrogel scaffolds have been used as vehicles to deliver cells to the NP, but their efficacy has been limited by brittleness, degradation, and swelling. This thesis focused on the development of amphiphilic, biohybrid hydrogels with controlled swelling for cell delivery.
The polymerization mechanisms for an amphiphilic poly(trimethylene carbonate) bearing methoxyethoxy side groups was investigated to allow for the synthesis of a well-defined backbone for the hydrogel. Monomer purity and catalyst selection were important factors in achieving a heterobifunctional architecture and predictable molecular weight as they could reduce the degree of autoinitiation during polymerization. These findings allowed for the synthesis of poly(trimethylene carbonate) bearing methoxyethoxy side chains with terminal methacrylate and vinyl sulfone groups. This heterobifunctional polymer could then be incorporated into a triblock copolymer with the pattern ABA, where A is the heterobifunctional polymer and B is a MMP cleavable peptide.
The triblock copolymer was crosslinked using ammonium persulfate and sodium bisulfite to initiate radical crosslinking. The thermal initiation system was minimally cytotoxic with cell viability above 75 % and did not cause side reactions with the peptide sequence. The resulting hydrogels were macroporous due to a thermoresponsive phase separation and were able to support NP cell proliferation and the deposition of collagen type II.
The triblock structure limited molecular weight control, as the copolymer depended on the molecular weight achieved in the preliminary ring-opening polymerization. To allow for more flexibility in a similarly modular system, a suite of multiblock copolymers with the pattern (AB)x, where is A is a synthetic polymer and B is the peptide, were synthesized. A base catalyzed thio-acrylate reaction was used to achieve chain extension of pre-synthesized A and B blocks. Using poly(trimethylene carbonate) and poly( -caprolactone) as model synthetic blocks, it was demonstrated that the extent of the chain extension depended on the size of the blocks but not on their composition. Preliminary assessment demonstrated the hydrophobic residues in the peptide created physical crosslinks leading to hydrogel formation.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.