Some of the current and recent research projects within the group. See Publications for more details about the outcomes of these studies.

Engineered Neural Tissue (EngNT) for peripheral nerve repair

EngNT technology provides a simple two-step method for the construction of aligned cellular materials that can act as artificial tissues. These have applications in regenerative medicine and as model tissues for research. Following initial development and successful testing of EngNT for peripheral nerve repair (Georgiou et al., 2013), more recent projects have focussed on translating the approach towards the clinic. This has involved close collaboration with clinical and commercial sector partners as well as academic researchers in Sweden, Belgium, Spain, Austria and the US. We have now generated EngNT using a range of clinically relevant cell types and materials and have developed production technology to facilitate future commercial and clinical applications.

Mathematical modelling to inform the design of repair constructs

In collaboration with Dr Rebecca Shipley‘s group (UCL Mechanical Engineering) we are taking an exciting new multidisciplinary approach to peripheral nerve injury research. Our aim is to combine experimental tools with mathematical modelling to inform the design of repair constructs. We are particularly interested in the role of both chemical (e.g. oxygen, growth factors) and mechanical cues (e.g. material stiffness) in influencing both neurite and vascular growth during peripheral nerve repair.

Drugs to improve regeneration and functional recovery following peripheral nerve damage

There is a clear clinical need to develop drug treatments that can improve outcomes in patients recovering from peripheral nerve injuries. We are using a range of advanced in vitro and in vivo models to explore small molecules that might promote regeneration and improve functional recovery. This programme of research includes experimental work conducted by Melissa Rayner in collaboration with Dr Jess Healy (UCL School of Pharmacy), and clinical translation conducted by Mr Tom Quick (consultant peripheral nerve surgeon, Royal National Orthopaedic Hospital).

Stabilising and repairing the damaged spinal cord

The aim of this research is to develop mechanically appropriate tissue-engineered constructs aimed at promoting repair and recovery of function. It involves understanding the mechanical environment of the spinal cord as well as constructing engineered tissues from biomaterials and therapeutic cells. This is a collaboration with Mr David Choi (UCL Institute of Neurology) and experimental work is being undertaken by Richard Bartlett.

Development of novel, robust 3D CNS tissue models for neurobiological studies and drug discovery

This project developed unique CNS tissue models and then used them to address specific neuroscience questions. It was a collaboration with TAP Biosystems and involved an innovative platform technology (RAFT™) for the generation of complex 3D model tissues. The model system used glial cells and neurons arranged within a hydrogel matrix to resemble living nervous system tissue. These models are now being used to monitor the responses of neurons and glia to simulated damage, and as a screening technology for potential neuroprotective therapies. The ultimate goal is that this type of technology will provide researchers in academia and industry with the means to produce robust and reliable tissue models that avoid the cost and variability associated with current 3D culture systems and will reduce their reliance on animal models.

Optimising photochemical internalisation to avoid neuronal toxicity

Photochemical Internalisation (PCI) is a novel drug delivery technology founded upon Photodynamic Therapy (PDT). In PCI, low dose PDT can selectively rupture endo/lysosomal membranes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release. PCI is currently being tested in patients at UCLH with advanced head and neck cancer (HNC) undergoing Bleomycin chemotherapy (more information). For PCI to be developed further, it is essential to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. This study aims to investigate the effect of PCI on mammalian peripheral nerve cells using advanced cell culture models, with proven utility for translational PDT research, to identify a PCI treatment approach that minimises nerve toxicity. The project is a collaboration with Dr Josephine Woodhams (UCL Surgery) and Mr Colin Hopper (Consultant Oral & Maxillofacial Surgeon) and the Research Assistant who worked on the project until 2016 was Caitriona O’Rourke.

Modelling and overcoming the biological interfaces that prevent nerve regeneration

Biological interfaces in the CNS that inhibit neuronal growth form around lesions, implanted spinal cord repair grafts and at the CNS-PNS boundary. This project aimed to understand and overcome these interfaces in order to improve neuronal regeneration during repair. The approach used was to develop powerful 3D culture models to understand interface formation and persistence. The models are now being used as a test-bed for developing novel therapies to overcome inhibitory interfaces and improve spinal cord repair. This project received funding from the Wellcome Trust and the postdoctoral researcher who worked on this project between 2007 and 2010 was Dr Emma East.

The response of astrocytes to cell and molecular therapies being developed to treat CNS injuries.

Understanding the response of astrocytes to potential treatments for CNS damage is important in the development of new therapies. Our 3D astrocyte culture models offer a useful means to assess changes in astrocyte reactivity. For example, potential cell therapies (e.g. stem cells) can be screened to determine the likelihood that they will elicit reactive gliosis in host astrocytes when administered to treat CNS damage. Furthermore, reactive gliosis and formation of a glial scar can be simulated in the models to enable the effect of potential treatments on this specific aspect of CNS damage to be understood.

Remodelling microglia in vitro in a 3D collagen construct

This was an international collaboration with Dr Sharmili Vidyadaran’s lab at Universiti Putra Malaysia to investigate microglial responses in 3D cell culture models. The PhD student who worked on the project (based in Malaysia) is Tong Chih Kong.

Modelling cellular responses to mechanical forces in the spinal cord

Developing advanced 3D cell culture and computational models to understand the response of spinal cord cells to forces generated during movement and impact. This is a multidisciplinary collaboration with Prof Richard Hall and Dr Joanne Tipper at University of Leeds and the PhD students working on the project are Jenny Smith and Stephen Goode.

Investigating the response of neural cells to debris from prostheses

This project uses cell culture models to explore the response of CNS cells to debris generated using simulated wear of spinal implants. It is a collaboration with Dr Joanne Tipper at University of Leeds and the PhD student working on the project is Helen Lee.

Peripheral nerve biomechanics

This project investigates the structural features of peripheral nerves that enable them to bend and stretch during normal movement without compromising their function. Understanding nerve biomechanics will not only give an insight into some fundamental anatomy, it will also be of value to clinicians treating nerve injury and physiotherapists involved in rehabilitation. The project has involved mechanical testing of nerve tissue, electron microscopy to investigate peripheral nerve ultrastructure and ultrasound imaging technologies to study variations in nerve movement at different anatomical locations in human volunteers. It has involved collaboration with physicists, engineers and surgeons and the PhD student who worked on the project until 2011 was Sarah Mason.

The effects of photodynamic therapy on the nervous system

Clinical observations have led to the suggestion that photodynamic therapy (PDT) may spare the nerve damage which is often associated with the surgical removal of tumours. This could make PDT particularly valuable in the treatment of cancers located within or adjacent to the nervous system. This project has explored the effects of PDT on cells of the nervous system by growing neurones in a 3-dimensional cell culture model to investigate the effects of a panel of photosensitiser drugs. Uptake, metabolism and mode of action of drugs can be studied using fluorescence microscopy, pharmacology and molecular approaches. This project benefits from a collaboration with the National Medical Laser Centre, UCL, providing an applied clinical aspect to a basic science project. The PhD student who worked on this ongoing project until 2009 was Kathleen Wright.

Selective detection and destruction of cancer cells

Cancer cells are often characterised by their rapid rate of division and over-expression of certain proteins, but many normal cells can also divide rapidly and express detectable levels of these same proteins. Consequently, current anti-cancer drugs cannot be used at their most effective concentration, for fear of destroying normal healthy tissues. This project aims to develop PDT approaches that preferentially target cancer cells, allowing tumours to be located and destroyed by focused laser illumination without affecting surrounding healthy tissues. This multidisciplinary project was supervised by James Phillips and Jon Golding in Life Sciences, and James Bruce in Chemistry at the OU, and benefits from collaboration with the National Medical Laser Centre, UCL. The PhD student who worked on this project until 2011 was Stanley Kimani.

Lanthanide complexes as reporters of drug induced toxicity

This industrial collaboration aims to develop and test luminescent lanthanide complexes as reporters of drug induced toxicity. It involves the design, synthesis and characterisation of novel lanthanide metal complexes targetted at specific cell organelles. The project involves synthetic chemistry and cell biology and is an interdisciplinary collaboration with James Bruce and Jon Golding at the OU and Andrew Nicholls at GlaxoSmithKline. The PhD student working on the project since 2013 is Bianca Vitiello.

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