Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Engineering Science

Program

Biomedical Engineering

Supervisor

Gillies, Elizabeth R.

Abstract

The development of tunable polymers has become increasingly important for both tissue engineering and drug delivery. This thesis investigates the development of water-soluble polyesters that contain both natural and synthetic components. These polymers offer tunable chemical structures, as well as functional groups for the conjugation of crosslinking moieties or cell signaling molecules. The first series of polymers was synthesized from poly(ethylene glycol) (PEG) and aspartic acid (Asp) via a titanium catalyzed transesterification method to provide polymers with molar masses of 12 kg/mol. After deprotection, the pendent functional groups of Asp were reacted with methacrylic, maleic, and itaconic anhydride to introduce crosslinkable functional groups. A thermally-initiated crosslinking method was used to prepare hydrogels from the methacrylamide-functionalized polymers. The resulting hydrogels were assessed based on their physical and mechanical properties. High cell content (> 95%) and Young’s moduli of 6 – 9 MPa were obtained were obtained for selected systems. Adipose derived stromal cells were encapsulated within these hydrogels and high cell viabilities indicated that they are promising as scaffolds for potential therapeutic or cell delivery. A second series of polyesters was prepared from PEG, Asp, and itaconic acid, thereby providing polymers with both crosslinkable moieties as well as functional groups for further bioconjugation. The backbone itaconate groups were crosslinked via thermally-initiated free radical crosslinking. Hydrogels were obtained, but the gel content was relatively low, indicating that further optimization of the polymer structure or crosslinking conditions will be needed in the future.

Summary for Lay Audience

Polymers offer an exciting area of research in the field of biomedical engineering because they can break down naturally in the body. This is especially important in the field of tissue engineering, which uses polymers to act as delivery vehicles for cells and drugs to enter the body. This thesis describes the formation of polymers that contain both amino acids and synthetic polymers. The combination of both natural and synthetic components can provide polymers that are both mechanically compatible with the body and non-toxic. The polymers were prepared containing components that can be obtained from renewable resources such as algae. To mimic the environment found within the body, these polymers are made to be water-soluble. They were then used to form a hydrogel, which is 3-dimensional network comprised of polymer chains. Hydrogels have a high-water content and mechanical properties which are similar to living tissue found within the body. The process used to form the hydrogel was initiated by heat, which potentially allows for the solution to be injected into the body as a liquid and form a gel once inside the body. Different polymer systems were used to synthesize various hydrogels and they were assessed based on their physical properties, such as how much the hydrogel swells. Hydrogels that formed a dense network were further analyzed. Stem cells derived from fat tissue were then encapsulated into the gel and the survival of the cells was assessed. The cells survived within the gel, which indicates that the gel itself is not toxic. Overall, this thesis lays the foundation for a new series of gel scaffolds that can be used to encapsulate cells and deliver them into the body.

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