Al-Fatlawi, Zainab Muhi;
(2025)
Development of a Tissue Engineered Three Dimensional (3D) Gingival Model to Replicate the Native Human Gingival Tissue.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Periodontal diseases, including gingivitis and periodontitis, and peri-implant mucositis are plaque-induced inflammations that can progress to irreversible tissue destruction. They result from poor oral hygiene and risk factors modifiable (e.g., tobacco, diabetes) and non-modifiable (e.g., age, genetics) influencing immune and inflammatory responses. Given the biological complexity and multifactorial nature of these conditions, in vitro models are essential for studying disease mechanisms and testing potential therapies. To evaluate the current state of such models, a systematic review was conducted, analysing 37 different 3D gingival and peri-implant models reported across 22 studies. However, no single model emerged as the best for studying 3D gingival or peri-implant tissues. Substrate selection is crucial for gingival model construction, requiring biocompatibility, porosity, and mechanical stability. Ten different substrates were reviewed, with most being animal derived. Rat tail collagen type I was the most frequent substrate used, supporting epithelial stratification but prone to shrinkage, high cost, and structural differences from human ECM. To identify potential target genes in periodontitis, NanoString GeoMx DSP was applied to tissue samples, comparing healthy and diseased gingival tissue. Results revealed similar functionally relevant gene expression in both tissues, providing novel insights for tissue characterization and laying the groundwork for developing a 3D gingival model as an in vitro tool using cell culture techniques. Experimental investigations evaluated candidate hydrogel biomaterials, focusing on gelatin methacryloyl (GelMA) and sodium alginate (SA) composites. Characterization demonstrated tunable mechanics, biocompatibility, and ECMmimicking features. Crosslinking methods (UV and CaCl₂) optimized scaffold stability and bioactivity. GelMA-SA composites supported fibroblasts and epithelial cells, with histological analysis confirming epithelial stratification and demonstrating superior structural integrity and cellular organization in specific formulations. Challenges remained with fibroblast migration, epithelial adhesion, and differentiation, particularly under air-liquid interface conditions, but the optimized composites provided a suitable microenvironment for gingival tissue engineering.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of a Tissue Engineered Three Dimensional (3D) Gingival Model to Replicate the Native Human Gingival Tissue |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215841 |
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