Soft tissue engineering has become increasingly relevant in efforts to create complex, functional tissues for tissue replacement in tissue engineering applications or for the development of more complex tissue models for drug screening or fundamental research. Tissue engineering of micro- and nano-scale structures has been explored through a number of biofabrication techniques but most successfully on the nano-scale through electrospinning. Electrospun nanofibers represent one of the most similar structures to natural extracellular matrix (ECM), while electrospinning of hydrogel nanofibers is particularly relevant given that such nanofibers support the high water content environment required by cells to survive. Herein, a reactive cell electrospinning process is demonstrated based on dynamic hydrazone-crosslinked poly(oligoethylene glycol methacrylate (POEGMA) hydrogel nanofibers that can be electrospun from an aqueous solution, allowing for the generation of cell-loaded hydrogel nanofibers in a single fabrication/cell-seeding step. Using the proper collectors, the fabrication of aligned and/or multi-layered scaffolds is demonstrated without the risk of layer delamination due to the dynamic crosslinking of POEGMA hydrogels. Co-electrospun NIH 3T3 fibroblasts and Psi2 12S6 epithelial cells were found to proliferate over 14 days within the networks, while electrospun C2C12 myoblasts were found to align along the direction of aligned fibers. POEGMA hydrogels provide a suitable environment for cells and can be expanded to multi-layer, multi-cellular networks with tunable micro-architectures to better mimic more complex aligned (e.g. muscle) and/or multi-layer (e.g. smooth muscle vasculature, esophageal) tissues. / Thesis / Master of Applied Science (MASc) / Successful regeneration of diseased tissues relies first on understanding the healthy tissue structures and functions that currently exist within the body, and second, how to synthetically replicate those structures using biomaterials. Re-creating the natural networks that cells use to attach and grow has many challenges, including the challenge of creating nano-scale structures, controlling any immune response to the biomaterial(s) used, and ensuring the correct response of cells to the fabricated structures. One method of generating suitable nano-scale structures is through a process called electrospinning, specifically when it is used to produce hydrogel-based nanofibers which can bind large amounts of water. When implanted, hydrogels swell to form a hydrated environment suitable for cells. These nanofibers are generated on a scale that is smaller than the encapsulated cells to allow for guided cell responses to the material. Furthermore, the use of cell-friendly polymer solutions allows for cells to be in contact with the biomaterial without resulting in high cell death. In this thesis, aligned and/or multi-layered nanofiber structures are generated to replicate the naturally existing support structures seen in the body. These fibers are also loaded with cells to create semi-functional body tissues that in the future can serve to replace non-functional tissues or used to better understand cell interactions with their environment.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28255 |
| Date | January 2023 |
| Creators | Dawson, Chloe |
| Contributors | Hoare, Todd, Chemical Engineering |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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