Design Strategies for Polysaccharide Hydrogels Used in Soft Tissue Engineering : Modification, Testing and Applications of Gellan Gum
Gering, Christine (2023)
Gering, Christine
Tampere University
2023
Biolääketieteen tekniikan tohtoriohjelma - Doctoral Programme in Biomedical Sciences and Engineering
Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology
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Väitöspäivä
2023-06-16
Julkaisun pysyvä osoite on
https://urn.fi/URN:ISBN:978-952-03-2901-3
https://urn.fi/URN:ISBN:978-952-03-2901-3
Tiivistelmä
Hydrogels are water-swollen polymer networks which provide an aqueous, three- dimensional environment and can mimic the biological cell environment and tissue architecture. Therefore, hydrogels are a valuable class of biomaterials for tissue engineering purposes that can be modified to support a specific application, such as the encapsulation of cells or as implantable device. Gellan gum is a microbial polysaccharide that readily forms self-supporting hydrogels in the presence of ions, and that has been investigated for medical applications due to its biocompatibility. However, due to its lack of innate cell recognition sites in its structure, gellan gum is highly inert and does not elicit any cell response required for in vitro cell culture or in vivo tissue integration.
Here, the possibilities to chemically modify gellan gum and render it bioactive for cell culture purposes are explored. The investigated modifications include purification, oxidation, reductive scissoring, as well as blending and chemical crosslinking, and are initially reviewed for their biocompatibility and ability to form hydrogels. The modified materials were assessed for their mechanical and viscoelastic properties, and basic cell response using the human fibroblast line WI-38. The cells were seeded either 2D on the surface of a gelated sample or encapsulated in the 3D hydrogel. Similarly, more advanced cell lines, such as human adipose stem cells, bone marrow-derived stem cells and a vascular co-culture model, were investigated using some of the formulations, and evaluated using different microscopic techniques. Furthermore, extrusion bioprinting was investigated as biofabrication method, and tissue response in vivo of cell-free hydrogels was ascertained by subcutaneous implantation.
In conclusion, the aim of thesis was to examine different modification approaches for the hydrogel gellan gum, but also to present a wholistic assessment protocol of modified hydrogel. Gellan gum acts as model polymer with the intent of projecting the design strategies and evaluation insights onto other polysaccharides and hydrogels. It has proven to be a suitable base polymer to create a material library with various mechanical and bioactive properties.
Here, the possibilities to chemically modify gellan gum and render it bioactive for cell culture purposes are explored. The investigated modifications include purification, oxidation, reductive scissoring, as well as blending and chemical crosslinking, and are initially reviewed for their biocompatibility and ability to form hydrogels. The modified materials were assessed for their mechanical and viscoelastic properties, and basic cell response using the human fibroblast line WI-38. The cells were seeded either 2D on the surface of a gelated sample or encapsulated in the 3D hydrogel. Similarly, more advanced cell lines, such as human adipose stem cells, bone marrow-derived stem cells and a vascular co-culture model, were investigated using some of the formulations, and evaluated using different microscopic techniques. Furthermore, extrusion bioprinting was investigated as biofabrication method, and tissue response in vivo of cell-free hydrogels was ascertained by subcutaneous implantation.
In conclusion, the aim of thesis was to examine different modification approaches for the hydrogel gellan gum, but also to present a wholistic assessment protocol of modified hydrogel. Gellan gum acts as model polymer with the intent of projecting the design strategies and evaluation insights onto other polysaccharides and hydrogels. It has proven to be a suitable base polymer to create a material library with various mechanical and bioactive properties.
Kokoelmat
- Väitöskirjat [4945]