Growth factor delivery systems and repair strategies for damaged peripheral nerves

Artificial nerve conduits (NCs) are, in certain cases, instrumental for repairing damaged peripheral nerves, although therapeutic efficacy remains often suboptimal. Considerable efforts have been made to improve the therapeutic performance of NCs. This article reviews recent developments in NC-technology for peripheral nerve regeneration with a main focus on growth factors delivery systems and repair strategies. Commonly used materials for NC fabrication include collagen, silk fibroin, and biodegradable aliphatic polyesters. The basic NC structure, i.e., a hollow tube, can be manufactured by diverse methods: spinning mandrel technology, sheet rolling, injection-molding, freeze-drying, and electro-spinning. Polymeric and cellular delivery systems for growth factors can be integrated in the NC wall or within luminal structures such as gels, fibers, or biological materials providing binding affinity for the bioactive compounds. NCs with sustained growth factor delivery generally improve significantly the axonal outgrowth in nerve defect models, although restoration of sensory and motor functions remains inferior to that achieved with autologous nerve grafts. To improve therapeutic outcomes, further biofunctionalization of NCs will be needed, i.e., adjusting degradation kinetics of NC scaffolding to be compatible with axonal regeneration; delivering multiple growth factors at individually optimized kinetics; incorporating modality specific glial cells and furnishing NCs with guiding nanostructures.