Decellularized nerve matrix hydrogel scaffolds with longitudinally oriented and size-tunable microchannels for peripheral nerve regeneration

The scaffolding biomaterials and their internal structures are crucial in constructing growth-permissive microenvironment for tissue regeneration. A functional bioscaffold not only requires sufficient extracellular matrix components, but also provides topological guidance by mimicry of the ultrastructure of the native tissue. In our laboratory, a decellularized nerve matrix hydrogel derived from porcine sciatic nerve (pDNM-G) is successfully prepared, which shows great promise for peripheral nerve regeneration. Herein, longitudinally oriented microchannel structures were introduced into pDNM-G bioscaffolds (A-pDNM-G) through controlled unidirectional freeze-drying. The axially aligned microchannels effectively directed and significantly promoted neurite extension and Schwann cell migration, assessed by culturing dorsal root ganglion explants on the longitudinal sections of A-pDNM-G scaffolds. Such regenerative cellular responses can be further optimized by tuning the channel sizes. In vivo studies confirmed that the implanted nerve guidance conduits containing A-pDNM-G scaffolds significantly facilitated axonal extension, myelination, and reached considerable functional recovery in 15-mm rat sciatic nerve defects. The incorporation of nerve growth factor further improved the overall performance in the grafted nerve. The bioactive pDNM-G enables controlled release of neurotrophic factor and easy integration of topological cue provided by the axially aligned microchannels into implantable bioscaffolds, which may serve in future clinical treatments of peripheral nerve injury.