Bridging the gap in peripheral nerve repair

Posted by Georgina Al-Badri on 20 September 2018

Degeneration and atrophy

The most common types of incident resulting in nerve damage, such as car accidents, mean the average patient with this type of injury is under 35. Peripheral nerve injuries are debilitating and can result in loss of function and chronic pain that can severely impact a patient’s quality of life.

Peripheral nerves – the nerves that connect the brain and spinal cord to the rest of the body – do have some natural regenerative capacity. Unfortunately, in ‘long gap’ injuries (large region of damage to the nerve, more than 1-2cm in length) the time required for that recovery means degeneration and atrophy in the region isolated by the damage at the injury site. This ‘wastage’ prevents successful regaining of function, hence clinical intervention is required.

The clinical gold standard for nerve repair in this case is an autograft – a nerve graft from the patient’s own body – which bridges the gap at the injury site, offering physical and chemical support to regenerating neurons. However, this solution can be accompanied by some loss of function due to nerve damage at the donor site. Furthermore, the patient has a finite supply of nerve tissue, which limits the size and number of possible repairs.

Such clinical techniques, despite only achieving 40-50% of sensory and motor function recovery, have changed very little in the past few decades, which firmly establishes peripheral nerve repair as a clinical problem that requires transformation.

Engineering neural tissue

Alternatives to the autograft have been a focus of research for many years. In collaboration with researchers from many disciplines at the UCL Centre for Nerve Engineering, my project aims to aid the development of a tissue-engineered solution to this clinical problem.

Engineered neural tissue is being developed by James Phillips group at the UCL School of Pharmacy. Composed of aligned therapeutic cells within hydrogel materials, it is designed to emulate the support offered by an autograft to guide neurite regrowth across the injury site.

My project primarily aims to address the question of vascularisation of engineered tissue, which becomes a key factor when considering the survival and functionality of therapeutic cells once implanted in the patient. Further to providing oxygen and nutrients, a vascular structure is likely to also play a leading role as a physical template in nerve regeneration, providing a guide for other cell types involved in the repair. I focus on the formation of capillary-like structures by cells in vitro, which can then connect with the patient’s own vasculature upon implantation.

The number of variables involved in the choice of in vitro culture conditions and scaffold properties would be costly and time-consuming to fully explore the effect of experimentally. We therefore take an interdisciplinary approach, combining mathematical, computational and experimental techniques.

Mathematical modelling seeks to identify the key mechanisms and variables in vascular network formation, offering a shortcut when combined with experimental data. This enables more efficient optimisation of culture conditions to produce a pre-vascularised engineered tissue. Applying this to engineered neural tissue aids the design of a clinically relevant tissue-engineered construct for peripheral nerve repair. 

Author

In the following table, contact information relevant to the page. The first column is for visual reference only. Data is in the right column.

Name: Georgina Al-Badri
Job title: Doctoral student
Department: Department of Mathematics
Organisation: University College London

Georgina Al-Badri is a first year doctoral student in the Department of Mathematics at UCL. During her undergraduate, she undertook summer projects that introduced her to the potential of combining mathematical with experimental techniques, which ultimately led to her decision to pursue similar research as a doctoral project.

Her doctoral project is funded by EPSRC via the National Productivity Investment Fund (NPIF), which offers funding for new places for doctoral training aligned to the government’s Industrial Strategy. The aim of the funding is to support highly skilled researchers and develop the talent needed by British industries for a thriving and innovation-led economy