Interfacing cells with microengineered scaffolds for neural tissue reconstruction

The development of cellular microenvironments suitable for neural tissue engineering purposes involves a plethora of research fields ranging from cell biology to biochemistry, neurosciences, physics, nanotechnology, mechanobiology. In the last two decades, this multi-disciplinary activity has led to the emergence of numerous strategies to create architectures capable of reproducing the topological, biochemical and mechanical properties of the extracellular matrix present in the central (CNS) and peripheral nervous system (PNS). Some of these approaches have succeeded in inducing the functional recovery of damaged areas in the CNS and the PNS to address the current lack of effective medical treatments for this type of injury. In this review, we analyze recent developments in the realization of two-dimensional and three-dimensional neuronal scaffolds following either top-down or bottom-up approaches. After providing an overview of the different fabrication techniques employed for tailoring the biomaterials, we draw on specific examples to describe the major features of the developed approaches. We then conclude with prospective proof of concept studies on guiding scaffolds and regenerative models on macro-scale brain implants targeting neural regeneration.