A new technology platform for neuro-regeneration: Next generation electroactive bioprostheses for spinal cord injury (SCI)

Repairing the injured spinal cord is a challenging task with several obstacles facing clinicians and scientists. This is because the injured spinal cord has very little ability to heal itself after injury. This means there are many serious and difficult consequences for patients and their carers, and a huge cost of care for the NHS.

The use of materials that can be surgically delivered into injury areas- in particular jelly-like structures called 'hydrogels' - have shown great promise for increasing repair in spinal injuries. These are soft materials which can be moulded into injury sites by clinicians, and allow for repairing cells in injury areas, such as nerve cells or blood vessels, to grow inside the implant.

Research has also shown that electrical stimulation that is currently used in clinical neuro-rehabilitation treatments can improve repair and movement after spinal injury. However, there is very little research that investigates combined use of soft hydrogels with electrical stimulation for spinal cord injury. The aim of this project is to lay the groundwork for development of highly sophisticated versions of hydrogels to function as devices that can be implanted into the patient and electrically stimulated to increase spinal repair. It will do this by allowing the applicant (a biologist with a background in repair of spinal cord injuries) to undergo a bespoke training programme with engineering teams at the University of Cambridge.

First, the applicant will be trained in the use of new digital printing methods to generate soft 3D hydrogels which have patterns created in them. The goal of the first stage is to create pattern 'guides' within the hydrogels which will help repairing cells grow in a particular, targeted direction, and recreate the organised structure of the spinal cord that has been disrupted by the injury.

In the second stage, the applicant will be trained in producing and testing soft materials that can deliver electrical stimulation.

The materials from the two stages will then be combined to create a 'hybrid implant' for delivery into the spinal cord, that is capable of guiding the growth of repairing nerve cells and be electrically stimulated at the same time. The approach we intend to take could lay the groundwork for the development of a very advanced class of materials that have a better ability to increase repair than the materials currently available. It is hoped that such work will result in a major new field of research to develop soft and electrically active implants for the repair of spinal cord injury, and develop new treatments for such injuries.

The potential future beneficiaries from this work are the following:

(1) Patients with spinal injury and their carers will benefit as this will be an important step in the development of novel classes of hybrid, patterned biomaterials and devices to optimize clinical use of implantable materials following injury. If successful, such an approach could have a significant impact on patient quality of life.

(2) Any effective clinical therapy that can be proven to enhance CNS repair, could reduce future costs to the NHS in terms of patient care and rehabilitation. Various biomaterials are being tested in clinical trials for neurological applications. Development of next generation versions of these materials, that can facilitate targeted cell growth and deliver electrical stimulation in rehabilitation protocols will be a novel and significant advance.

(3) The use of patterned and electroactive materials can be expanded easily to the repair of other types of pathology for example in Parkinsons disease and stroke, for delivery of stem cells in encapsulating materials with electrical stimulation. In addition, materials/devices can be used effectively in both the neonatal and adult CNS in a range of experimental model organisms and be expanded to the study of regenerative mechanisms in peripheral nerve injury and disease.

(4) If the new hybrid materials can be further developed and tested in collaboration with industrial partners, particularly those developing electroceuticals and novel devices for clinical rehabilitation or polymer biomaterials for regenerative applications, then this could have commercial implications for the UK economy by development of new business ventures and investment opportunities.

(5) Polymer chemists will benefit as the work will identify parameters in terms of stiffness matching and patterning of hydrogel based implants. This work can then be expanded to test a range of polymers and pattern combinations for different neuro-regenerative applications. Potentially, such materials will find wider application for regeneration in pathologies such as orthopaedic injuries.

(6) The project will take an important step towards establishing a cross disciplinary and cross university collaboration, for development of novel neuromaterials. Through the impact programme specified, the applicant intends to lay the foundations for development of a UK network of complementary researchers in the Physical and Life Sciences, investigating new materials and the repair of neurological injuries. The impact programme also outlines outreach activities to educate school students in the next generation of materials for neural injury, and medical interventions of the future.

(7) The applicant has a background in repair of spinal injuries. This project will provide her with an invaluable training opportunity to gain an interdisciplinary understanding of cutting edge approaches to develop new strategies for spinal repair.

(8) Future generations of student engineers and life scientists will benefit through the training and educational impact activities identified, and will benefit from engagement with a highly novel area of research.