Students

I am working on the manufacturing of light-controlled soft robots. These are not the classically known robots made of steel and wires. On the contrary, they are hydrogels made soft and squishy, yet tough and elastic. The greatest feature is their application as smart scaffolds for tissue engineering.

My project involves the development of artificial membrane binding proteins (AMBPs) for the modification of synthetic vesicles to enhance in vivo cardiovascular repair. My project involves the rational design and comprehensive biophysical characterisation of both the vesicles, AMBPs and modified vesicles. This work is a step towards building a modular homing system to target synthetic vesicles towards various specific sites in vivo.

My research project is focused on the development of a smart microporous biological 3D printable ink (bioink) that can be used in both in vitro and in vivo tissue engineering. The structural component of the bioink is a viscoelastic hydrogel that has a highly tuneable temperature-dependent phase transition. In practice, this allows it to be extruded from nozzles (e.g. a needle) as a liquid at room temperature, which subsequently transforms into a self-supporting hydrogel at body temperature. Housed within this biomaterial-based hydrogel, is a cell-free expression system, which can be developed to produce growth factors that are essential for bone healing. Significantly, the delivery of these factors will be controlled using transcription regulation, such that the growth factor expression levels can be systematically modulated. The resulting smart bioink will be 3D printed in the presence of mesenchymal stem cells to control differentiation. This method of stem cell differentiation stimulation into osteoblasts has potential as a powerful technique in tissue engineering research and as a clinical tool for bone fracture repair.

3D response of cancer to chemotherapies can be modelled using cancer spheroids, which grow from single cancer cells in a 3D matrix. High throughput bioprinting, coupled with high content microscopy and image analysis, allows for the screening of different therapeutic combinations against thousands of cancer spheroids in a controlled manner. In the future, this approach could be used to reduce the need for animals in drug testing, or to personalise cancer therapies for patients by analysing treatment combinations to find an optimal therapy.

My research work is in the area of 3D-printable engineered living materials (ELMs). ELMs are a type of biohybrid material that combine whole living cells with non-biological components/scaffolds. The idea is to combine the best of both worlds. The autonomous capabilities of cells with the tractability of synthetic materials (may they be polymers/gels/ceramics/metals etc.) to create materials with novel biologically-derived feedback properties and embedded intelligence. In my project, I aim develop a 3D printable E. coli-laden bioink ELM. This will become a new platform for patterned bacterial microreactor synthesis (constructs augmented with the abilities of transformed E. coli). Current bacterial microreactor applications being investigated include organophosphate bioremediation and hybrid gel synthesis.

Periodontitis is an oral disease characterised by the persistent inflammation of periodontal tissues which, if left untreated, ultimately leads to alveolar bone dissolution and tooth loss. My project aims to create an in vitro model of the human periodontium in order to elucidate potential growth mechanisms which may inform the development of regenerative therapies. This work combines bioprinting and tissue engineering approaches to generate a 3D tissue model amenable to high throughput testing.

My doctoral and postdoctoral work has centered around building a 3D model of the renal glomerular filtration barrier, using conditionally immortalised podocytes and endothelial cells first established at the University of Bristol. I broadly followed two approaches to achieve this aim, one using 3D bioprinting and the other using fibrin gels and protein engineering. In the latter, I co-developed a method generating 3D fibrin scaffolds from purified and modified thrombin. By chemically modifying thrombin so it had a surfactant corona, the enzyme could be embedded in the membrane of several cell types. In the presence of fibrinogen in solution, this membrane bound thrombin would form a hydrogel from the very surface of the cells, serving as a kind of extracellular matrix (ECM) mimic. Conditionally immortalised podocytes and endothelial cells in these 3D fibrin gels produced ECM specific to the glomerular basement membrane, which was verified using lightsheet microscopy. The second major aim of my PhD was to develop new 3D bioprinting methods to build a 3D renal model. I have also developed methodologies relating to fluorescence imaging (namely confocal microscopy), image processing, electron microscopy and immunohistochemistry.

I’m working on the fabrication of engineered living materials towards the development of bioreactors. This project involves the 3D bioprinting of bacteria laden hydrogels that can be precisely deposited into predesigned architectures. These structures both shelter the cells and maintain their metabolic function. The genetic tractability of bacteria permits the expression of a wide range of recombinant enzymes to tailor these materials for bespoke application in bioremediation.

Cytoseek Partnered Project