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Title: Engineering a tissue mimic for predictive nanoparticle assessment
Author: Tan, N. S.
ISNI:       0000 0004 5359 2433
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Bio-scientific research has relied heavily on models of cell monolayers cultured on plastic. For most cell types, this does not represent their in vivo tissue organisation well. As a result they behave differently in vitro from in vivo, leading to poorly predictive data. Plastic compression (PC) of collagen is used to engineer constructs with more tissue-like conditions. The aim of this study was to test the feasibility of using these constructs as a three-dimensional tissue model for assessing the fate of hyaluronan nanoparticles (HA-NP). Collagen hydrogels were seeded with cells and HA-NP and subjected to PC. Due to their small size, HA-NP retention following PC was investigated. HA-NP uptake by cells was then compared to conventional monolayer cell cultures. 19.1±1.2% of the initial HA-NP load was retained following PC, which could be increased to 31.1±3.1% by multi-layering. This entrapment was found to be largely physical as HA-NPs were released from the construct following cellular remodeling, but not without it. Cells in monolayer reached their maximum HA-NP uptake in 3 days whilst cells in collagen peaked at 7 days. This maximum uptake was 60.1 a.u., twice as large as that of 3D-cultured cells (32.8 a.u). A novel method was developed to analyse local collagen densities which revealed particular collagen distributions in micro-patterned constructs depending on the shape of template used; round grooves had a 21.4±4% increase in collagen density at their bases, whilst rectangular grooves displayed two peaks corresponding to their internal corners, which were 15.2±4% and 16.9±3% denser than the unpatterned regions. This work has enabled greater understanding of the PC and micro-moudling which will aid in creating more complex tissue constructs in a predictable and controlled way. The importance of 3D tissue organisation in in vitro models, particularly for nanoparticle testing, has also been demonstrated in this work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available