Novel thermoresponsive particle gels for tissue engineering applications

Cheikh Al Ghanami, Racha (2011) Novel thermoresponsive particle gels for tissue engineering applications. PhD thesis, University of Nottingham.

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Biomaterials play an important role in tissue engineering, where they are used as scaffolds for the 3D culture of cells, to help the generation of neo tissues in-vitro and achieve superior tissue engraftment and regeneration in-vivo.

The work presented in this thesis describes how thermoresponsive particle gels, a class of materials not previously investigated for tissue engineering applications, can find important applications in this field.

The main gels developed and studied were the aqueous thermoresponsive particle gels prepared from poly(poly(ethylene glycol) methacrylate ethyl ether) (polyPEGMA246-EE) together with polycaprolactone (PCL) microparticles.

The thermoresponsive polymer polyPEGMA246-EE, synthesised by free radical polymerisation, was employed as an adsorbing steric stabiliser for polycaprolactone microparticles prepared by the single emulsion solvent evaporation method. The resulting suspensions exhibited reversible temperature induced gelation based on incipient flocculation, where they switched from being free flowing at temperatures below 19°C to form space filling gels at body temperature (37°C) over periods of ~1 minute. On cooling, the suspensions returned to a fluid state.

The viscoelastic properties of the particle gels could be controlled by varying the temperature and composition, enabling these gels to be tailored for specific applications.

Using NIH3T3 as a model cell line, PCL/polyPEGMA246-EE particle gels exhibited key characteristics advantageous for the 3D culture of cells. These were mainly the ability to assemble around the cells at temperatures, above the LCST of polyPEGMA246-EE, and the provision of a supportive scaffold with appropriate mechanical properties for growth, along with good cytocompatibility enabling cell spreading and proliferation over extended culture times, as well as the rapid return to a flowable state on cooling allowing for suspension transfer, for cell subculture and harvesting, without the need for enzymes. The latter property would also allow for the injectable delivery of the in-vitro conditioned cell-gel constructs for therapeutic applications.

Another variant of thermoresponsive particle gels has also been presented in this thesis. Thermoresponsive magnetic-particle gels were developed from the combination of magnetic polystyrene microparticles and the thermoresponsive polymer polyPEGMA246-EE.

These exhibited reversible thermogelling behaviour which allowed for cell encapsulation, while their magnetic sensitivity allowed for cell recovery through simple magnetic particle separation.

The novel concept of scaffold deconstruction by temperature, and cell recovery through magnetic-particles separation is significant for applications where a scaffold-free outcome would be desired such as the commercial expansion of therapeutic cells.

In this thesis, the preparation and application of first generation biocompatible thermoresponsive particle gels is described.

The combination of ease of preparation, the potential for scale-up and positive cell response make thermoresponsive particle gels promising as a new class of materials for applications in cell culture, as supports for tissue growth and in cell delivery systems.

The materials developed and studied in this thesis are believed to represent a significant contribution to the fields of biomaterials, drug delivery and tissue engineering.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Alexander, C.
Shakesheff, K.
Keywords: Biomaterials Tissue engineering Colloid particle gel microparticle scaffolds 3D cell culture Thermoresponsive
Subjects: R Medicine > R Medicine (General) > R855 Medical technology. Biomedical engineering. Electronics
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 12318
Depositing User: EP, Services
Date Deposited: 13 Jul 2012 19:38
Last Modified: 20 Dec 2017 19:52

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