Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering
<p>Elastin, although a small constituent of heart valves, plays a significant role in its functionality and the maintenance of tissue homeostasis. It is due to its low abundance that its significance has been overlooked in favour of collagen and glycosaminoglycans. However, repeatedly, the fai...
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| Format: | Thesis |
| Language: | English |
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2020
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| _version_ | 1797107370252304384 |
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| author | Iftekhar, S |
| author2 | Czernuszka, J |
| author_facet | Czernuszka, J Iftekhar, S |
| author_sort | Iftekhar, S |
| collection | OXFORD |
| description | <p>Elastin, although a small constituent of heart valves, plays a significant role in its functionality and the maintenance of tissue homeostasis. It is due to its low abundance that its significance has been overlooked in favour of collagen and glycosaminoglycans. However, repeatedly, the failure of biological prostheses has been associated with the disruption of elastic fibres. The incorporation of exogenous forms of elastin has been challenging due to the intrinsic insolubility and poor processability of polymeric forms. This has led to the precedence of applications of soluble forms of elastin, which, although are tailorable, do not offer sufficient structural integrity or bioactivity (once cross-linked).</p>
<p>This thesis reports a method for the isolation of a novel form of natural elastin, termed Fibrillar Elastin Gel (FEG), which was discovered during the course of the DPhil. A method was developed to modify polymeric elastin to a processable form with improved polymer-solvent interactions. FEG is a thermally induced aggregated gel, composed of rod-like fibres (4-6µm) with improved intermolecular interactions as shown by the appearance of a shoulder at 1618cm-1 by infrared spectroscopy. The material exhibits a low loss factor (~0.1 at 1Hz) and has been hypothesised to be applicable as a biomaterial for tissue engineering of heart valves. </p>
<p>Porous (>94%) scaffolds of multiple compositions were fabricated by freeze-casting. Swelling studies revealed a negative thermosensitivity and contraction of FEG above the inverse transition temperature (30°C). Tensile testing showed a strong positive correlation between the concentration of FEG and the strain-to-failure of composites which increased from 37% to 94% as the concentration increased. In vitro studies revealed FEG contains cell-binding sites and did not hinder the attachment or viability of induced pluripotent stem cell-derived cardiomyocytes. The elastogenic capability of FEG was assessed by studying the gene expression of lysyl oxidase (LOX), elastin (ELA), and fibrillin-1 (FIB-1) which upregulated significantly on scaffolds with higher FEG content, suggesting that FEG would be a suitable material to use to design templates that promote elastogenesis. In addition, layer-specific tri-layer scaffolds were shown to stimulate layer-specific gene expression of extracellular matrix markers such as collagen type I (COL), hyaluronan synthase-2 (HAS-2) and ELA. Tri-layer scaffolds exhibited a non-linear mechanical response as well as bending anisotropy, a key deformation characteristic of native valves. </p>
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| first_indexed | 2024-03-07T07:13:37Z |
| format | Thesis |
| id | oxford-uuid:42f9e8f1-76dc-42d5-97a6-f7c01ca3f20a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:13:37Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | oxford-uuid:42f9e8f1-76dc-42d5-97a6-f7c01ca3f20a2022-07-27T14:38:20ZIsolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineeringThesishttp://purl.org/coar/resource_type/c_db06uuid:42f9e8f1-76dc-42d5-97a6-f7c01ca3f20aBiomaterialsEnglishHyrax Deposit2020Iftekhar, SCzernuszka, J<p>Elastin, although a small constituent of heart valves, plays a significant role in its functionality and the maintenance of tissue homeostasis. It is due to its low abundance that its significance has been overlooked in favour of collagen and glycosaminoglycans. However, repeatedly, the failure of biological prostheses has been associated with the disruption of elastic fibres. The incorporation of exogenous forms of elastin has been challenging due to the intrinsic insolubility and poor processability of polymeric forms. This has led to the precedence of applications of soluble forms of elastin, which, although are tailorable, do not offer sufficient structural integrity or bioactivity (once cross-linked).</p> <p>This thesis reports a method for the isolation of a novel form of natural elastin, termed Fibrillar Elastin Gel (FEG), which was discovered during the course of the DPhil. A method was developed to modify polymeric elastin to a processable form with improved polymer-solvent interactions. FEG is a thermally induced aggregated gel, composed of rod-like fibres (4-6µm) with improved intermolecular interactions as shown by the appearance of a shoulder at 1618cm-1 by infrared spectroscopy. The material exhibits a low loss factor (~0.1 at 1Hz) and has been hypothesised to be applicable as a biomaterial for tissue engineering of heart valves. </p> <p>Porous (>94%) scaffolds of multiple compositions were fabricated by freeze-casting. Swelling studies revealed a negative thermosensitivity and contraction of FEG above the inverse transition temperature (30°C). Tensile testing showed a strong positive correlation between the concentration of FEG and the strain-to-failure of composites which increased from 37% to 94% as the concentration increased. In vitro studies revealed FEG contains cell-binding sites and did not hinder the attachment or viability of induced pluripotent stem cell-derived cardiomyocytes. The elastogenic capability of FEG was assessed by studying the gene expression of lysyl oxidase (LOX), elastin (ELA), and fibrillin-1 (FIB-1) which upregulated significantly on scaffolds with higher FEG content, suggesting that FEG would be a suitable material to use to design templates that promote elastogenesis. In addition, layer-specific tri-layer scaffolds were shown to stimulate layer-specific gene expression of extracellular matrix markers such as collagen type I (COL), hyaluronan synthase-2 (HAS-2) and ELA. Tri-layer scaffolds exhibited a non-linear mechanical response as well as bending anisotropy, a key deformation characteristic of native valves. </p> |
| spellingShingle | Biomaterials Iftekhar, S Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering |
| title | Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering |
| title_full | Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering |
| title_fullStr | Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering |
| title_full_unstemmed | Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering |
| title_short | Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering |
| title_sort | isolation of fibrillar elastin gel feg and its application in heart valve tissue engineering |
| topic | Biomaterials |
| work_keys_str_mv | AT iftekhars isolationoffibrillarelastingelfeganditsapplicationinheartvalvetissueengineering |