Bridging the lesion-engineering a permissive substrate for nerve regeneration

Biomaterial-based strategies to restore connectivity after lesion at the spinal cord are focused on bridging the lesion and providing an favourable substrate and a path for axonal re-growth. Following spinal cord injury (SCI) a hostile environment for neuronal cell growth is established by the activation of multiple inhibitory mechanisms that hamper regeneration to occur. Implantable scaffolds can provide mechanical support and physical guidance for axon re-growth and, at the same time, contribute to alleviate the hostile environment by the in situ delivery of therapeutic molecules and/or relevant cells. Basic research on SCI has been contributing with the description of inhibitory mechanisms for regeneration as well as identifying drugs/molecules that can target inhibition. This knowledge is the background for the development of combined strategies with biomaterials. Additionally, scaffold design is significantly evolving. From the early simple hollow conduits, scaffolds with complex architectures that can modulate cell fate are currently being tested. A number of promising pre-clinical studies combining scaffolds, cells, drugs and/or nucleic acids are reported in the open literature. Overall, it is considered that to address the multi-factorial inhibitory environment of a SCI, a multifaceted therapeutic approach is imperative. The progress in the identification of molecules that target inhibition after SCI and its combination with scaffolds and/or cells are described and discussed in this review.