RESUMO
The treatment of spinal cord injury aims to reconstruct the fiber connection and restore the interrupted neural pathways. Adipose mesenchymal stem cells (ADSCs) can promote the recovery of motor functions in spinal cord injury. However, poor survival of ADSCs and leakage outside of the injury site after local transplantation reduce the number of cells, which seriously attenuates the cumulative effect. We performed heterotopic transplantation on rats with severe spinal cord injury using human ADSCs loaded within self-assembly hydrogel RADA16-RGD (R: arginine; A: alanine; D: aspartic acid; G: glycine). Our results indicate that the combined transplantation of human ADSCs with RADA16-RGD improved the survival of ADSCs at the injured site. The inflammatory reaction was inhibited, with improved survival of the neurons and increased residual area of nerve fibers and myelin protein. The functional behaviors were promoted, as determined by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale score and electrophysiological measurements. ADSCs can promote the repair of spinal cord injury. This study provides new ideas for the treatment of spinal cord injury.
RESUMO
The harsh local micro-environment following spinal cord injury (SCI) remains a great challenge for neural regeneration. Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable functions has thus been an area of concern. Herein, a hybrid hydrogel was developed using Fmoc-grafted chitosan (FC) and Fmoc peptide (FI). Dynamic reversible π-π stacking interactions of the fluorenyl rings enabled the FC/FI hybrid hydrogel to exhibit excellent injectable and self-healing properties, as characterized by visual appearances and rheological tests. Furthermore, the FC/FI hybrid hydrogel showed a slow and persistent release of curcumin (Cur), which was named as FC/FI-Cur hydrogel. In vitro studies confirmed that with the support of FC/FI-Cur hydrogel, neurite outgrowth was promoted, and Schwann cell (SC) migration away from dorsal root ganglia (DRG) spheres with enhanced myelination was substantiated. The FC/FI-Cur hydrogel well reassembled extracellular matrix at the lesion site of rat spinal cord and exerted outstanding effects in modulating local inflammatory reaction by regulating the phenotypes of infiltrated inflammatory cells. In addition, endogenous SCs were recruited in the FC/FI-Cur graft and participated in the remyelination process of the regenerated nerves. These outcomes favored functional recovery, as evidenced by improved hind limbs movement and enhanced electrophysiological properties. Thus, our study not only advanced the development of multifunctional hydrogels but also provided insights into comprehensive approaches for SCI repair.
RESUMO
Electrical stimulation (ES) can be used to manipulate recovery after peripheral nerve injuries. Although biomaterial-based strategies have already been implemented to gain momentum for ES and engineer permissive microenvironments for neural regeneration, the development of biomaterials for specific stimuli-responsive modulation of neural cell properties remains a challenge. Herein, we homogeneously incorporate pristine carbon nanotubes into a functional self-assembling peptide to prepare a hybrid hydrogel with good injectability and conductivity. Two-dimensional (on the surface) and three-dimensional (within the hybrid hydrogel) culturing experiments demonstrate that ES promotes axon outgrowth and Schwann cell (SC) migration away from dorsal root ganglia spheres, further revealing that ES-enhanced interactions between SCs and axons result in improved myelination. Thus, our study not only advances the development of tailor-made materials but also provides useful insights into comprehensive approaches for promoting nerve growth and presents a practical strategy of repairing peripheral nerve injuries.
