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The strategy of using a combination of scaffold-based physical and biochemical cues to repair spinal cord injury (SCI) has shown promising results. However, integrating conductivity and neurotrophins into a scaffold that recreates the electrophysiologic and nutritional microenvironment of the spinal cord (SC) remains challenging. In this study we investigated the therapeutic potential of a soft thermo-sensitive polymer electroactive hydrogel (TPEH) loaded with nerve growth factor (NGF) combined with functional electrical stimulation (ES) for the treatment of SCI. The developed hydrogel exhibits outstanding electrical conductance upon ES, with continuous release of NGF for at least 24 days. In cultured nerve cells, TPEH loaded with NGF promoted the neuronal differentiation of neural stem cells and axonal growth, an effect that was potentiated by ES. In a rat model of SCI, TPEH combined with NGF and ES stimulated endogenous neurogenesis and improved motor function. These results indicate that the TPEH scaffold that combines ES and biochemical cues can effectively promote SC tissue repair.

Although the mortality rates of patients suffering from spinal cord injury (SCI) have decreased as the modalities of clinical therapy have been improved, the recovery of motor and sensory functions remains a challenge, ultimately leading to paraplegia or quadriplegia. Recently, neural tissue engineering scaffolds with appropriate physical and biological functions have been extensively developed to promote nerve regeneration and improve motor and sensory functions during SCI therapy. In this work, we summarized the physical support and bioelectrical signal conduction of polymer scaffolds for SCI repair from the aspects of biocompatibility, biodegradation, internal structure, mechanical performance, and conductivity. In addition, the biological functions of the polymer scaffolds were reviewed for the reversal of adverse pathophysiological factors to improve the microenvironments of the injured site and promote endogenous neurogenesis during SCI therapy. Moreover, the future development of these engineered scaffolds for potential clinical applications was predicted.