3d micro-structured collagen conduits for nerve repair

Abstract

Introduction. Peripheral nerve injury leads to sensation and movement loss that is devastating to the patient. In cases of complete nerve transection (neurotmesis), it is often necessary to use an autologous nerve graft to bridge the injury site. Various attempts have been made to develop artificial conduits that can replace autologous grafts, but such conduits are usually only effective at bridging short gaps. Here, we have developed and tested a new form of nerve repair conduit, based on 3D microstructured collagen. Methods. Two forms of conduit were fabricated using different thicknesses of plastic compressed collagen sheet. Low density (LD) guidance-surface conduits were made from spiralling a single standard thickness (100ìm) collagen sheet. High density (HD) conduits were made from spiralling three thin collagen sheets. The HD conduits have 3x as many layers (and guidance interface) as the LD conduits. For assessment in vivo, a segment of the rat sciatic nerve was removed and a HD or LD conduit (0.5 cm in length) was implanted. Separate control experiments involved either direct repair of a sciatic nerve injury by coaptation, or insertion of an autologous graft. At 2 weeks, the implanted conduit and attached proximal and distal nerve portions were removed, fixed in formaldehyde and processed for immunocytochemistry. Results. Transverse and longitudinal sections revealed immunoreactive axons within the conduits, with axons confined to the interfaces between the spiralled collagen sheets. In the same regions an extensive cellular infiltration was present, which included numerous Schwann cells. Conclusions. The results indicate that interfaces between spiral layers of plastic compressed collagen can act as guidance and support structures for Schwann cell migration and axon regeneration. Ongoing studies are analysing the differences between the HD and LD conduits, and the topographical cues that maximise axon growth