Kyoseva, Ana Yuliyanova (2022) A novel scaffold for cell-based lung tissue engineering. Doctoral thesis, Keele University.

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Abstract

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and numbers are rising. Tissue engineering approaches have the potential to improve lung function and treat diseases such as COPD. Our aim is to investigate a highly porous and elastic gelatine scaffold, Surgispon®, for potential uses in cell-based lung tissue engineering by generating an alveolar-like structure. Surgispon scaffolds were crosslinked for stability, and their pore size, pore connectivity, and cytotoxicity were investigated. Human lung epithelial (A549) and fibroblast (35FLH) cell lines and primary porcine lung cells were cultured on Surgispon scaffolds, both separately and in co cultures. Surgispon was used to create an airliquid interface (ALI) to differentiate primary lung cells, and migration studies were performed in combination with decellularised lung tissue. Uncrosslinked Surgispon dissolved rapidly in solution, crosslinking promoted stability beyond 60 days in cell culture conditions. Pore size and interconnectivity were determined via imaging and μCT analysis, establishing similarity to alveolar diameter. Surgispon scaffolds supported cell attachment and growth, with no requirement for chemical coating. Primary lung epithelial cells differentiated into ciliated cells and self-organised into bronchospheres/organoids when cultured on Surgispon with an ALI. Cell migration occurred both from scaffold to tissue and vice versa, demonstrating the potential use of Surgispon scaffolds in clinical COPD research. In summary, Surgispon® scaffolds are an effective alveolar mimic due to being suitable for 3D cell culture, differentiation, and featuring interconnective pores of a size approximate to alveolar diameter. These features promote the prospect of Surgispon scaffolds as a potential scaffold and/or cell delivery system for use in lung tissue engineering and to help combat respiratory disease.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Contributors: Forsyth, NR (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 17 Mar 2022 09:01
Last Modified: 17 Mar 2022 09:01
URI: https://eprints.keele.ac.uk/id/eprint/10377

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