Nervous system repair

Repair devices are designed to encourage growth of host neurons through an area of damage. They don’t contain any neurons, but often include aligned materials and glial cells in order to guide and support regenerating neurons. They need to be made from materials and cells suitable for safe therapeutic use, and as well as promoting neuronal growth they must restore the biomechanical functionality of the tissue.

Engineered Neural Tissue for nervous system repair

Engineered neural tissue mimics key features of cellular and extracellular nervous system components. Rather than culturing cells within artificial biomaterial scaffolds, glial cells are maintained within a natural extracellular matrix hydrogel. Careful control of their mechanical environment causes the glial cells to align (using the same principles described for aligned tissue models), then plastic compression is used to stabilise the aligned tissues.

 

 

 

The result is a robust hydrogel material packed with highly aligned glial cells that can support and guide neuronal regeneration (see Georgiou et al., 2013 and Phillips 2014).

A flat sheet of Engineered Neural Tissue contains aligned glial cells (green) that support and guide neuronal regeneration

Sheets of this versatile cellular biomaterial can be rolled into fibres and packed together to form a stable repair conduit.

Repair devices fabricated in this way can be tailored towards repair of specific parts of the nervous system. This involves selecting the appropriate glial cell type and adapting the extracellular matrix components to ensure integration of the implant and support of neuronal regeneration. For example we have used differentiated stem cells from adipose tissue and dental pulp as components of engineered neural tissue.

Self-aligning tissue growth guide for peripheral nerve repair

Peripheral nerve repair devices have been developed that supply aligned Schwann cells in a collagen gel, tethered within an outer tube.

The self-aligning tissue growth guide (Patent WO2004087231) has been tested using a silicone tube as the outer element in a preclinical model of peripheral nerve injury.

Regenerating neurons (green) grow through the implanted repair device (left), supported and guided by aligned Schwann cells (red, centre) and penetrate the distal stump (right).

Our current aim is to identify clinically relevant sources of Schwann cells for incorporation into this device, and to replace the silicone tube with a resorbable material.

 

 

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