Thesis
Functionalised gelatin for vascular graft sealant applications
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T16908
- Person Identifier (Local)
- 201989705
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Gelatin is one of the most widely used biopolymers with many desirable properties including: it is biodegradable, non-toxic, biocompatible, non-immunogenic, easily modified and exhibits good cell adhesion. These characteristics are often tailored and applied in the food, biomedical and pharmaceutical industries. Gelatin hydrogels are often used in the medical field for tissue engineering, drug delivery and as sealants in medical devices. Gelatin is formed by the partial hydrolysis of collagen. The resulting gelatin material is naturally polyampholytic, dissolves readily in water and forms a thermoreversible sol-gel upon cooling. The behaviour of these hydrogels is influenced by the charges located on the amino acid side chains throughout the gelatin molecules. The presence and distribution of ionisable side chains influences the surface activity of gelatin and ultimately determines the material properties. Side chain modifications can also be performed to achieve the optimum hydrogel properties. Physical gelatin hydrogels are held together by non-covalent interactions which can easily be broken down above 30 °C. Therefore, chemical crosslinking is often carried out to introduce strong covalent interactions into the gelatin network, improving the material mechanical properties and thermal stability. When acting as a vascular graft sealant, the role of gelatin is to decrease the permeability of the graft upon implantation and to serve as a temporary scaffold for cell attachment. The sealant is gradually resorbed by the patient during healing and replaced with human tissue. The infiltration of human tissue is dependent on the extent of crosslinking within the sealant. Therefore, the sealant and its degree of crosslinking influence the patient healing process. The initial aim of this research was to develop a greater understanding of gelatin modifications, with a primary focus on the succinylation modification at the ε-amino group of lysine. The reaction conditions were investigated by altering the pH and mass of reagents. When strict pH was maintained throughout the duration of the reaction, consistently high levels of modification were achieved. Once optimised at the laboratory scale, these reaction parameters were implemented in a series of development runs at pilot scale for company material validation studies. The succinylation reaction was also successful at this scale and subsequent development work focussed on material purification solutions. The ionisable side chains present throughout gelatin influences the material properties of the hydrogel and makes them susceptible to changes at various pH values and salt concentrations. The influence of pH and salt species on the mechanical properties and underlying material morphology were investigated. When adjusted to more acidic or alkaline pH values, larger swelling ratios and softer gelatin blocks were observed due to unbalanced surface charges and increased electrostatic repulsion. Conversely, at pH values close to the isoelectric point, the materials exhibited lower swelling ratios and firmer gelatin blocks due to balanced surface charges and minimised electrostatic repulsion. These Coulombic interactions dictate the hydrogel properties. The presence of salt species of different concentrations and valency were also found to have an influence on gelatin properties. The ionic species had the largest influence on material swelling, while gelatin block firmness and gelling temperatures were only notably impacted at the highest salt concentration tested. It was very difficult to discern any distinct trends from the data as the values fluctuated. However, it was observed that divalent salt species had more of an impact on the hydrogel properties compared to the monovalent salts. The multivalent salt species displayed crosslinking abilities that limited gelatin solubility. Alternative side chain modifications were performed and optimised to study the influence of different side chain chemistries on the hydrogel properties. As with the succinylation reaction, the modifications were reproducible when strict pH was maintained and high degrees of modification were achieved. As a result of different side chain hydrophilicity and steric bulk, the materials exhibited different swelling behaviour, mechanical properties and specific rotation. Glyoxal crosslinking was explored as an alternative to formaldehyde. However, after glyoxal crosslinking the materials exhibited different trends in terms of material swelling and firmness. Inverse swelling behaviour was observed, while hydrogel softening was exhibited by all samples. To satisfy the manufacturing element of this PhD, vascular grafts were made using laboratory succinylated gelatin. The 50:50 blend of non-succinylated and laboratory succinylated gelatin was an effective sealant for the Terumo Aortic Gelweave™ vascular grafts. The sealant blend showed excellent properties, preventing blood leakage while degrading within the required timeframe.
- Advisor / supervisor
- Liggat, John J.
- Davidson Christine M.
- Resource Type
- DOI
- Date Created
- 2023
- Embargo Note
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File | 2024-05-07 | Embargo |