MIMIT seminar series - nerve repair

Regenerating nerves after injury: A novel polymer conduit for peripheral nerve repair –
Professor Sandra Downes

The human nervous system is made of the peripheral and the central nervous system. Damage to the peripheral nerve can lead to loss of sensation and function and affects about 1 in 1000 people. Nerve repair is an ongoing area of research and damage to the peripheral nerve can be repaired and regenerated unlike the central nerves. Current methods involve nerve autography but this process is ineffective with a number of problems such as loss of function at the donor site, sub optimal recovery and grafts are often the wrong diameter. A better method is required and tissue engineering allows the combination of cell based therapies with biomaterials.

Previous work has shown that nerve regeneration can be enhanced by using artificial nerve conduits to transplant Schwann cells; which are essential for repair as they multiply rapidly, secret growth factors and clear debris. Clinical use of Schwann cells is limited however as sufficient numbers are hard to produce in a short time and so methods are being sought to solve this problem. Alternative methods would be to use adult multi-potent stem cells that can be differentiated into functional Schwann cells for therapeutic use. There are other ongoing projects investigating nerve repair and results from different materials used will hopefully help to produce a scaffold with the best properties. The aim of this study was to create a polymer conduit that protects the nerve during healing and as the nerve repairs itself, the conduit degrades overtime.

The biocompatibility and biodegradability of the conduit are essential points and the group produced a novel material composition along with a new seal of the conduit. The material has a unique molecular structure that allows the conduit to degrade from the surface inwards, thus avoiding an acidic burst of polymers such as PCA. The conduit is minimally invasive, non toxic, sterilized, low cost, highly efficient and has a controllable microenvironment. It allows the ability to control surfaces, grow Schwann cells and nerve cells together and attract the appropriate growth factors. Early preclinical work in rats has shown no scarring, correct muscle attachment and a lack of inflammation. The nerve regeneration was illustrated by staining nerves with antibodies to show the area of cell repair. This early work has allowed FDA approval and further physiology tests, such as the grip test can be run on animals to see of the functionality of the nerves has been restored.

With FDA approval already in place, the conduits can be patented and have tremendous commercial potential. The route to market has been identified as producing a cluster of patents that can be licensed out to appropriate manufacturers. Future aims are to develop the material to improve directional growth and patent these new surfaces. Work on topographical nerve direction has already begun using processes such as in vitro testing, photolithography and wet etching. There is also the possibility of making the conduits electro-conductive in order to help directional growth and kick start nerve activity. Other ideas are to use the conduit to repair nerves in the central nervous system and tackling problems such as optical nerve blindness in newborns. To conclude, the conduit is a suitable solution to a current clinical problem and has many opportunities for future development and applications.