Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Chemistry

Supervisor

Gillies, Elizabeth

2nd Supervisor

Flynn, Lauren

Co-Supervisor

Abstract

Tissue engineering using adipose-derived stromal cells (ASCs) shows promise for soft tissue regeneration. Biodegradable polymers are potential biomaterials as they support the growth and delivery of cells. Specifically, poly(ester amide)s (PEAs) are a class of biodegradable polymers with tunable structures that have been shown to exhibit low cytotoxicity and support the growth of various cell types. This thesis involved the development of new water soluble amino acid-based PEAs with crosslinkable moieties to enable formation of hydrogel scaffolds for ASC encapsulation. These hydrophilic phenylalanine-based and alanine-based PEAs were synthesized by solution polycondensation and photo-crosslinked into a series of hydrogels with and without poly(ethylene glycol) dimethacrylate, methacrylated chondroitin sulphate or decellularized adipose tissue, and hydrogel properties including gel content, equilibrium water content, and swelling were examined. ASC viability and adipogenesis were studied in selected PEA hydrogels, and the overall results demonstrated the potential of these new water soluble PEAs as biomaterials for adipose tissue engineering, as they provided a supportive environment for ASCs survival and adipogenic differentiation in culture.

Summary for Lay Audience

Using cells to regenerate lost or damaged tissues is a promising alternative to current transplant approaches. In particular, adipose-derived stromal cells (ASCs), which can be isolated from waste fat tissue, are a special type of cells that can be converted into fat cells, and hold promise for fat regeneration for soft tissue reconstruction and cosmetic plastic surgery purposes. To aid in the delivery of these cells into the body and to support their growth, materials that are able to break down into nontoxic elements can be used to hold the cells. In this project, we have picked a class of materials called poly(ester amide)s (PEAs) that are capable of producing nontoxic components as they break down. The PEAs were made to be able to dissolve in water and to contain specific chemical features in order to form a hydrogel, which is a gel material that can take in a large amount of water and resembles the structure of soft tissues such as fat. ASCs were incorporated in these PEA hydrogels and observed for their behaviors inside the gels in terms of their survival and conversion to fat cells. However, using natural biological materials can often help with directing cell behaviors. Therefore, we added a material that has features similar to the environment of fat cells called decellularized adipose tissue (DAT) to the PEA hydrogels, which was also extracted from fat tissue. DAT was proposed to provide beneficial qualities to the overall hydrogels and better support the survival and fat cell conversion of the ASCs inside the gels. Based on the results, we found that the ASCs inside the hydrogels made from PEAs and PEAs with DAT survived well in culture and were able to convert into fat cells. As a result, the materials that we developed in this work showed potential to be used for fat regeneration.

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