Targeted tissue engineering: hydrogels with linear capillary channels for axonal regeneration after spinal cord injury

Abstract

Spinal cord injury (SCI) frequently results in the permanent loss of function below the level of injury due to the failure of axonal regeneration in the adult mammalian central nervous system (CNS). The limited intrinsic growth capacity of adult neurons, a lack of growth-promoting factors and the multifactorial inhibitory microenvironment around the lesion site contribute to the lack of axonal regeneration. Strategies such as transplantation of cells, delivery of bioactive compounds and gene transfer have been investigated as a means to promote axonal regrowth through the lesion, to form new synaptic connections and to improve functional outcomes. Although growth of some axonal populations can be robustly enhanced by cellular implants alone or in combination with neurotrophic factors, axons usually extend in random orientation and even reverse growth direction in the lesion site (Figure 1A) (Gros et al., 2010; Günther et al., 2015). Thus, regenerating axons often fail to approach the distal edge of the lesion site, a pre-requisite for proper contact with spared host neurons. The lack of a 3-dimensional organization in the injury site is therefore an additional barrier for successful axonal bridging. Two approaches, physical guidance through structured scaffolds and chemical guidance by growth factor gradients, have emerged as potential means to provide directional cues for axonal growth through the lesion.