Abstract
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.
Highlights
Spinal cord injury (SCI) disrupts the connection between the brain and peripheral organs, leading to sensory motor dysfunction [1]
Characterization of Poly(ethylene glycol) methyl ether (mPEG)‐PLV‐TA copolymer The electroactive copolymer was synthesized by condensation crosslinking of mPEG-PLV and capped aniline tetramer (CTA)
All peaks in the copolymer were clearly assigned (Fig. 1A), demonstrating successful synthesis
Summary
Spinal cord injury (SCI) disrupts the connection between the brain and peripheral organs, leading to sensory motor dysfunction [1]. The endogenous bioelectric signals and neurotrophins in the spinal cord (SC) are indispensable in maintaining. Liu et al J Nanobiotechnol (2021) 19:286 to promote endogenous neurogenesis for SCI repair. Hydrogels are an ideal candidate scaffold for this purpose because of their high water content, biocompatibility, 3-dimensional (3D) porous structure, and mechanical properties similar to SC, which meet the requirements of nerve cell adhesion, metabolic substance exchange, and bioactive substance loading for SC regeneration [11, 12]. Hydrogel scaffolds have electrical conductivity and can simulate the electrophysiologic environment of nerve tissue in combination with exogenous ES. Hydrogels have been used for nerve repair through the delivery of small molecule drugs in a rat brachial plexus injury model [13]
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