Saudi Cultural Missions Theses & Dissertations
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Item Restricted Corneal Expansion for Blindness Prevention(Imperial College London, 2020-09) Banaama, Saeed; Stevens, MollyCorneal shortage is a major issue, which limits the number of corneal transplant procedures performed worldwide. It is estimated that only one cornea is available per every seventy needed. Approximately 200,000 vision-saving CTs take place annually worldwide, but there are another 12 million people waiting for corneas. The majority of these patients are located in India and China. The number of people in need of corneas is expected to rise due to the aging population. Corniplex has developed a novel approach for addressing this shortage using stem cell and regenerative medicine technologies. There are currently no biosynthetic corneas on the market. The product is currently in the development stages and the preclinical trials are expected to be completed in 2024. The device is classified as a combination product under FDA guidelines and is anticipated to enter the market in 2030, following the successful completion of an international phase III clinical trials. Corniplex is targeting India as its initial market. We anticipate annual peak sales in 2040, with revenues reaching up to $7 million dollars annually. To achieve this objective, we attempted to optimise the printing conditions of Gelatin Methacryloyl (GelMA) , one of the most widely used materials in bio-applications due their biocompatibility and biodegradability profile. In the technical part of this thesis, the photo-rheology of GelMA is investigated to determine its suitability to be used as a bioink in Stereolithography based 3D printing. The impact of changing the degree of functionalisation (DOF, 42 vs. 93%), photoinitiator concentration (0.2-1% wt), and GelMA concentrations (50, 100, and 200 mg/mL) on growth rate and time to halfway point (thwp) is examined and compared semi-empirically using a Gompertz function. The results show a higher growth rate (0.007 vs. 0.01) and a decrease in thwp with higher photoinitiator concentration (394 vs. 240 s) – indicating a more rapid polymerisation. Higher GelMA concentrations showed a higher growth rate for lower concentrations (0.025 at 50 mg/mL vs. 0.01 for 100 and 200 mg/mL). On the other hand, the increase in GelMA concentration resulted in decrease to thwp (315 vs. 196 s, for 50 and 200 mg/mL, respectively). The greatest effect of the DOF was observed at 200 mg/mL with regards to thwp (210 vs. 280 s, the former being the sample with 93% DOF). The growth rate was slightly higher in the samples with higher DOF in the 100 mg/mL GelMA. However, this effect seems to subside with the 200 mg/mL GelMA, indicating the possibility that DOF is might be less relevant with higher GelMA concentrations.21 0Item Restricted The Utilisation of GelMA-based Surface-patterned Scaffolds for Craniofacial Muscle Regeneration Applications(University College London (UCL), 2024-03-28) Aljaber, Mohammad; Knowles, JonathanIn the circumstances of volumetric muscle loss of craniofacial muscles, which can happen due to accidents, for instance, the functionality of muscle tissue could be completely lost. Although muscle flap surgery is the current standard treatment utilised, a novel approach is the use of “tissue engineering” in which scaffolds, cells and additional biomolecules are exploited to aid the muscle regeneration process. In this project, gelatin methacryloyl (GelMA) was synthesised and optimised for muscle regeneration applications. Various parameters involved in the reaction, such as reaction time and methacrylic anhydride (MA) concentration, GelMA concentration, photo-initiator concentration and ultraviolet (UV) exposure time were optimised. The mechanical and biological properties were evaluated and reported for a number of formulations/processing conditions. The data suggested that using 10-15% (w/v) GelMA mixed with 0.1% (w/v) LAP and crosslinked for 2 minutes had the optimum balance between mechanical and biological properties for skeletal muscle regeneration applications. The investigation also thoroughly examined the impact of both the source and the bloom number of gelatin on the properties of the laboratory-synthesised GelMA. Specifically, porcine, bovine, and fish-derived gelatin sources were evaluated, along with porcine gelatin of 175 versus 300 bloom number. Extensive assessment of the mechanical and biological characteristics was carried out using various techniques. The results concluded that bovine-derived GelMA demonstrated superior mechanical properties compared to other groups, while no significant differences were observed in terms of biological properties. All groups showed relatively high metabolic activity and low LDH release which suggests high cell viability and a low cytotoxic response. Additionally, the ability of GelMA hydrogels (derived from porcine, bovine or fish) to promote myoblast differentiation of C2C12 muscle cells and myotube formation was evaluated. Results showed that all groups succeeded in promoting differentiation of myoblasts into myocytes and myotubes, and presented similar myogenesis ability with no significant differences after 21 days of differentiation. A key challenge in skeletal muscle regeneration is enhancing the alignment of the myocytes and myotubes. Therefore, three-dimensional (3D) printed moulds with specific sizes of grooves and ridges (300 µm, 600 µm or 900 µm) were printed using biocompatible commercial resin before GelMA hydrogels and C2C12 cells were cast in the moulds and crosslinked via UV. The influence of these patterns was characterised using DAPI and phalloidin F-actin staining to study the impact of the surface patterns on the alignment of myotubes. The Z-stack images obtained by confocal microscope illustrated that using surface patterns of 300 µm helped in improving the alignment of myotubes in comparison with the other groups. To this end, the investigation of GelMA hydrogels from different species concluded that bovine-GelMA (B-GelMA) presented the greatest mechanical properties in which all groups presented excellent biological properties in terms of promoting cell growth and attachment, as well as cellular differentiation into myocytes and myotubes. The surface pattern of 300 µm grooves and ridges demonstrated the highest cell and myotube alignment compared to larger-sized grooves and ridges. In addition, this myotube alignment, as documented by the RT-qPCR, led to enhanced gene expression of MyoG and MyoD-1.9 0