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Strategies for neural tissue repair heavily depend on our ability to temporally reconstruct the natural cellular microenvironment of neural cells. Biomaterials play a fundamental role in this context, as they provide the mechanical support for cells to attach and migrate to the injury site, as well as fundamental signals for differentiation. This review describes how different cellular processes (attachment, proliferation, and (directional) migration and differentiation) have been supported by different material parameters, in vitro and in vivo. Although incipient guidelines for biomaterial design become visible, literature in the field remains rather phenomenological. As in other fields of tissue regeneration, progress will depend on more systematic studies on cell-materials response, better understanding on how cells behave and understand signals in their natural milieu from neurobiology studies, and the translation of this knowledge into engineered microenvironments for clinical use.

The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant.