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Title: Development of thermoresponsive polymeric hydrogels as in vitro 3D cell culture matrices
Author: Mahboubian, AliReza
ISNI:       0000 0004 6423 3962
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2015
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Historically, the examinations of cell and tissue physiology and pathophysiology have been carried out in 2D cell cultures outside of the human body. However, recently, it has been demonstrated that the functionality of cells cultured in two dimensions is very different to that of similar cells cultured in three dimensional cell cultures. Also cells cultured in three dimensions can represent better the native tissue. Therefore, it is important to create 3D growth conditions that can mimic a native tissue closely in vitro. Some 3D models have been developed, however, they are typically costly to prepare, have a complex 3D preparation method, or originates from animal sources with significant batch to batch variations. Hence, there is a general need to develop new 3D cell models with a simple preparation process and reliable performance that are cost effective. Initially in this research, a series of physical blends composed of hyaluronic acid (HA) and cellulose derivatives were prepared and screened in terms of gel formation with different salt excipients using an inverted vial test and turbidity measurements. As a result, methylcellulose (MC) A15, a thermoresponsive polymer, was selected as a polymer with promising characteristics. Furthermore, the effect of HA and salt excipients at various concentrations on the final MC-HA hydrogel characteristics was then further investigated, by means of turbidity, stability, rheology, and morphology measurements. The optimal combinations of components and conditions to produce a stable MC-HA hydrogel at 37°C i.e., 5.0 and 7.0% w/w MC, 0.45-2.00% w/v HA and 0.159 mol Li sodium citrate (SC) were selected. The stability, in terms of number of washes after which the gel preserved its structure, increased with increasing concentration of HA in the hydrogel. Also, rheology data (deformation oscillatory shear measurements) indicated that the combination of HA with MC enhances the elastic material response of the hydrogel. In terms of morphology, the addition of HA at a level between 0.22 and 0.45% w/v produced a mesh-like structure, while at higher concentrations no explicit structure was noticed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available