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Title: Multilayer poly(glycerol sebacate urethane) scaffold with biomimetic properties for oral mucosa tissue engineering
Author: Samourides, Andreas
ISNI:       0000 0004 7964 537X
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
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Defects in the oral cavity, caused from gingival recessions, trauma, chronic infections and oral cancer, have demonstrated a great challenge to treat because of the limitation of donor oral tissue. Oral mucosa tissue engineering is a science that aims to engineer a three-dimensional oral mucosa able to reconstruct the native oral mucosa tissue to treat defects in the oral cavity. Within the tissue engineering field biomaterials are used, called scaffolds, to support and promote the cell growth. Until now, no synthetic scaffolds have been used for oral mucosa tissue engineering clinically. Thus, the aim of this thesis was to develop synthetic poly(glycerol sebacate urethane) (PGSU) scaffolds that mimic the native oral mucosa's structure for potential oral mucosa tissue graft. Large three-dimensional PGSU scaffolds were successfully fabricated, demonstrating high porosity and water permeability. The freeze drying protocol was characterised, illustrating that the pore size, pore structure and mechanical properties can vary significantly between different protocols. However, the porosity and water permeability were not affected by the freeze drying protocol. The scaffolds were sterilised and found that these scaffolds were not affected by the sterilisation method, however, the microstructure and mechanical properties of the scaffold were not suitable for tissue engineering oral mucosa tissue. To optimise both the microstructure and mechanical properties of the scaffold the polymer concentration was altered and the freeze drying technique improved. It was found that the pore size and porosity of the scaffolds could be closely controlled using these techniques which led to the generation of scaffolds with improved mechanical properties. The scaffolds made with higher polymer concentration had smaller pore sizes and porosity but higher mechanical properties. The enhanced mechanical properties of the scaffolds were closer to the oral mucosa's biomechanical properties and it was demonstrated that the shape and strength of the scaffolds can be recovered after loading. During in vitro cell culture the cell metabolic activity significantly increased over time and the microstructure did not affect the metabolic activity but did affect the cell distribution. The cells could not penetrate the smaller pore size scaffolds; therefore the cell distribution was poor. Cells deposited significantly more collagen in scaffolds with higher porosity compared to those which were less porous during in vitro cell culture. In the final chapter more complex scaffold structures were fabricated by combining freeze drying, mould technology and airbrushing fabrication techniques. Novel PGSU isotropic, anisotropic and hierarchical multilayer scaffolds were developed by altering the freeze drying mould while a two-layer scaffold with a layer that mimics the basement membrane of the oral mucosa was generated using airbrushing. The basement membrane-like layer of the scaffold successfully acted as a cell barrier with limited infiltration from the epithelium layer and a multilayer epithelium was evident after co-culture with oral fibroblasts. The collagen production from the multilayer scaffold was higher than the one-layer scaffolds characterised previously in this study. In this thesis we fabricated a synthetic, elastomeric, biomimetic PGSU scaffold with potential to be used in oral mucosa tissue engineering and other areas of soft tissue engineering.
Supervisor: Hearnden, Vanessa ; Biqiong, Chen ; Claeyssens, Frederik Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available