Development of gelatin-silica hybrid hydrogels for bone tissue engineering and in vitro modelling

Lewns, Francesca K (2024). Development of gelatin-silica hybrid hydrogels for bone tissue engineering and in vitro modelling. University of Birmingham. Ph.D.

Lewns2024PhD.pdf Text - Accepted Version Restricted to Repository staff only until 1 August 2026. Available under License All rights reserved. Download (33MB) | Request a copy

Abstract

Naturally derived biopolymers have received considerable attention for use as hydrogel materials for tissue engineering due to their innate ability to mimic the natural extracellular matrix. However, low mechanical strength and uncontrolled degradation limit their use within bone tissue engineering applications. Hybrid hydrogels are interpenetrating networks of organic and inorganic moieties and, when made via sol-gel processing, present an attractive route to address the drawbacks of biopolymers. Hybrid hydrogels can be classified as Class I (weak non-covalent interactions) and Class II (covalent bonds) depending on the interactions between the organic and inorganic component. This thesis presents the development of gelatin-silica organic-inorganic hybrid hydrogels using various organosilane crosslinkers to functionalise gelatin to provide covalent coupling of the organic and inorganic moieties. The efficiency and degree of functionalisation of gelatin with organosilane crosslinker were studied with various techniques (\(^1\)H NMR spectroscopy, ninhydrin assay and titration). Significant challenges with the functionalisation reaction, including hydrolysis and condensation of trimethoxysilyl groups, led to a lack of efficiency and low degree of functionalisation. A novel alternative method was developed to synthesise organosilane-functionalised gelatin; the reaction was rapid. Mechanical tests revealed the yield stress and toughness significantly increased in Class II hydrogels during ageing, suggested to be due to the continuous formation of a covalent network. However, the compressive mechanical properties of the hybrid systems were still far from those of bone (15 to 20 MPa). CryoSEM imaging revealed subtle differences in the microarchitectures of the different hydrogel formulations. When seeded on the Class II hydrogels, Saos-2 cells demonstrated improved cell spreading over a seven-day culture when imaged using actin/DAPI staining and cell penetration to depths of up to ~2,300 um as observed by light sheet fluorescence microscopy, compared to the Class I hydrogel. It is hypothesised that the dynamic mechanical properties and differences in microarchitecture of the Class II hydrogels, compared to Class I, were able to influence cell behaviour. Thus, the hybrid materials developed in this thesis could be utilised in soft tissue applications, as well as minimally invasive injectable hydrogels in spinal fusion and fracture repair.

Type of Work:	Thesis (Doctorates > Ph.D.)
Award Type:	Doctorates > Ph.D.
Supervisor(s):	Supervisor(s) Email ORCID Poologasundarampillai, Gowsihan UNSPECIFIED UNSPECIFIED Cox, Liam UNSPECIFIED UNSPECIFIED Grover, Liam UNSPECIFIED UNSPECIFIED Wildman, Ricky UNSPECIFIED UNSPECIFIED
Licence:	All rights reserved
College/Faculty:	Colleges (former) > College of Medical & Dental Sciences
School or Department:	School of Dentistry
Funders:	Medical Research Council
Subjects:	Q Science > Q Science (General) R Medicine > RK Dentistry T Technology > TP Chemical technology
URI:	http://etheses.bham.ac.uk/id/eprint/15089

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