Hydrogels have been widely explored for cell therapy applications due to their favourable
biochemical and mechanical properties. However, the dimensions of bulk hydrogels limit
the diffusion of nutrients to cells and cell products to the surrounding environment,
negatively affecting cell viability and the therapeutic potential of the encapsulated cells. In
addition, invasive procedures are often required for the administration of bulk hydrogels
into patients that pose a practical barrier to cell therapy. To address these issues, micrometer
sized hydrogels (microgels) have been designed with controlled shapes, sizes, and
structures to enable sufficient biomolecule diffusion and injectable administration. In this
thesis, in situ gelling poly(oligoethylene glycol methacrylate) (POEGMA) and zwitterionic
microgels are fabricated based on delayed dynamic hydrazone crosslinking between cell friendly functionalized polymers without the need for any additional crosslinking agents.
Two microgel fabrication strategies were explored: (1) droplet-based microfluidics and (2)
droplet extrusion printing. In the first case, microgels with controlled degrees of porosity
were fabricated via the incorporation of a non-toxic evaporable porogen into a microfluidic
device. Porous microgels had significantly improved diffusion of small molecules
compared to nonporous microgels, and cells encapsulated in the porous microgels showed
significantly increased viability over 10 days. In the second case, droplet extrusion printing
was employed to print a bioink on a hydrophobic surface, resulting in the fabrication of
disk-shaped microgels with a height below the maximum pathlength of oxygen and nutrient
diffusion. Cells encapsulated in the microgels maintained high viability, with the microgels
also supporting effective cell proliferation over 10 days. Overall, the work presented in this
thesis poses solutions to challenges around nutrient/cell product diffusion and the invasive
procedures typically associated with hydrogel-based cell therapy, providing potentially new
translatable therapeutic options for disease treatment. / Thesis / Master of Applied Science (MASc) / Cell therapy is used to improve or replace the function of damaged cells or tissues that
currently exist in the body by delivering healthy cells and the therapeutic products they
naturally produce to the site of interest. Delivering these cells to the body has many
challenges, including attacks from the immune system and substantial cell death caused by
mechanical forces applied upon injection. To overcome these problems, the cells can be
loaded into hydrogel-based microparticles (microgels), highly hydrated polymer networks
that can protect the encapsulated cells from the immune system and mechanical forces
while providing an environment that can support cell viability and growth. This thesis is
focused on designing microgels with suitable dimensions and structures that allow for
nutrients to flow from the environment to the cells and wastes/cell products from the cells
to the environment while also supporting long-term cell viability, allowing the therapeutic
molecules the cells produce to potentially treat diseases.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29881 |
| Date | January 2024 |
| Creators | Neely, Laura |
| Contributors | Hoare, Todd, Biomedical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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