Currently an autograft is the gold standard for peripheral nerve injuries that cannot be repaired by surgical suturing. Autografts remain insufficient for full recovery from a large injury to the sciatic nerve or brachial plexus nerves. Synthetic nerve guidance conduits (NGCs) have been investigated for these injuries  to guide axonal regeneration and lead to functional recovery. We have designed a hydrogel multi-channel conduit with defined microscale features to guide axonal outgrowth. To aid vascular infiltration into the conduit and integration with the regenerating axons, we also designed a multi-channel conduit with defined regularly spaced micropores along the side wall, orthogonal to the guidance channels. Using our in-house continuous digital light projection 3D printing platform, we are able to fabricate each hydrogel conduit within minutes from a milliliter prepolymer vat. With our state-of-the-art printing platform, we have achieved NGCs with a consistent channel wall width of 10 microns. The NGC mechanical properties can be tuned during the printing process by varying the photoinitiator concentration and light intensity. We implanted the NGCs for 16 weeks in a murine sciatic nerve transection injury model. The mice transgenically express CFP in their motor and sensory neurons for visualization. We assessed the functional recovery by dynamic gait analysis throughout the recovery period and by compound muscle action potential (CMAP) electrophysiology before NGC harvesting. Additionally, the neural tissue regeneration was assessed via histology for axon density, myelination, and vascularization.

Bottom-up design of a 3D-printed multi-microchannel nerve conduit for axonal guidance and vascular integration

ACS Spring Meeting 2021

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