Chitosan tubes help regenerate peripheral nerves

In contrast to the central nervous system, peripheral nerves show regenerative capacities. However, regeneration after substantial nerve loss is very poor and can lead to loss of function of the interacting muscle. This necessitates the development of innovative therapies for repair and regeneration of peripheral nerve injuries.

The EU-funded BIOHYBRID (Biohybrid templates for peripheral nerve regeneration) project is developing a device to enable long-distance repair of injured nerves. This novel graft device made of Chitosan, a biopolymer present in the shell of crabs, is designed to overcome the gap due to lost nerve tissue and activate nerve regeneration between the proximal and distal nerve stumps. An integrated experimental approach includes prefabrication of a biohybrid nerve device, its transplantation into nerve gaps in an animal model and evaluation of the regenerative outcome.

After three years of work, BIOHYBRID partners tested 3D scaffolds based on chitosan hollow tubes. One comprehensive and one medium-scale in vivo study evaluating chitosan hollow tubes with different degrees of acetylation resulted in the Reaxon® Nerve Guide, approved as a medical device.

In vitro studies of scaffold functionalisation showed that iron oxide nanoparticle-conjugated neurotrophic factors convey the necessary properties to the scaffolds, resulting in a patent application. In vivo evaluation revealed that seeding the scaffold with fibroblast growth factor-2 overexpressing Schwann cells promoted axonal regeneration. The differences in peripheral nerve regeneration between healthy and diabetic, male and female rats were also characterised.

BIOHYBRID developed a comprehensive clinical investigation plan for evaluating repair of median and ulnar nerve lesions in humans using an implanted Reaxon® Nerve Guide. The Reaxon® Nerve Guide was implanted in a few patients with peripheral nerve defects in Germany after its market entry in June 2014. The results of the clinical trial will support future applications of advanced composite chitosan conduits. Clinical use of the developed innovative bio-engineered nerve device is expected to shorten recovery times and speed up return to quality of life for affected patients.