In situ injectable hydrogels for spinal cord regeneration: advances from the last 10 years

Spinal cord injury (SCI) is a tremendously devastating disorder with no effective therapy. Neuroprotective strategies have been applied aiming to prevent secondary cell death but no successful and robust effects have been observed. Recently, combinatorial approaches using biomaterials with cells and/or growth factors have demonstrated promising therapeutic effects because of the improvement of axonal growth and in vivo functional recovery in model organisms. In situ injectable hydrogels are a particularly attractive neuroregenerative approach to improve spinal cord repair and regeneration since they can be precisely injected into the lesion site filling the space prior to gelification, decrease scarring and promote axon growth due to the hydrogel's soft structure. Important advances regarding the use of hydrogels as potential therapeutic approaches has been reported during the last 10 years. Injectable alginate hydrogel loaded with GDNF, thermoresponsives heparin-poloxamer loaded with NGF and imidazole-poly(organophosphazenes) hydrogels are just three examples of biomaterials that can promote neurite, axon growth and improve functional recovery in hemisected and resected rats. Here we will review the status of in situ injectable hydrogels for spinal cord regeneration with special focus in the advantages of using hydrogel scaffolds, the ideal polymers to be used, the gelification process and the cells or growth factors combined. The in vitro and in vivo results reported for those biomaterials will be presented, compared and discussed.