Bioengineered Zinc Oxide Nanoparticle-Loaded Hydrogel for Combinative Treatment of Spinal Cord Transection.

Sen Lin,Chang Xu,Shu-Rui Chen,Da-Hao Wang,Zi-Peng Zhou,Xi-Fan Mei,Hao-Sen Zhao

doi:10.3389/fbioe.2021.796361

Sen Lin, Chang Xu + Show 5 more

Open Access

https://doi.org/10.3389/fbioe.2021.796361

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Abstract

Spinal cord injury (SCI) is one of the most destructive diseases. The neuroinflammation microenvironment needs comprehensive mitigation of damages. Thus, regulation of local, microenvironment drugs could be a potential effective treatment. However, clinical studies on SCI with common treatment have reported it to cause systemic toxicity and side effects. Zinc oxide nanoparticles (ZnONPs) have been widely reported to have satisfying anti-inflammation function. Furthermore, green synthesis procedures can improve the capability and possible utilization of ZnONPs. However, the efficient administration and underlying mechanism of ZnONPs in SCI treatment remain unclear. Herein, an innovative approach was built by utilizing ZnONPs loaded in a skeletal muscle-derived adhesive hydrogel (ZnONPs-Gel). Different from the systemic application of ZnONPs, the local administration of ZnONPs-Gel offered the ZnONPs-loaded extracellular matrix with beneficial biocompatibility to the injured spinal cord, thereby promoting effective function recovery. Mechanistically, the ZnONPs-Gel treatment not only markedly reduced ROS production but also decreased apoptosis in the injured spinal cord. Therefore, the strategy based on local administration of the ZnONPs-Gel in the early stage of SCI may be an effective therapeutic treatment.

Highlights

Spinal cord injury (SCI) is a destructive disease of the central nervous system (CNS) (McDonald and Sadowsky, 2002), accompanied by motor and/or sensory dysfunctions
The result showed that green production of Zinc oxide nanoparticles (ZnONPs) significantly reduced cell toxicity
The results indicated that the injured spinal cord tissue repaired by ZnONPs-Gel exhibited a higher expression of Tuj1 in different segments, accompanied by fewer astrocytes

Summary

INTRODUCTION

Spinal cord injury (SCI) is a destructive disease of the central nervous system (CNS) (McDonald and Sadowsky, 2002), accompanied by motor and/or sensory dysfunctions. Local application of ZnONPs will ameliorate the inflammatory microenvironments and attenuate injured spinal cord dysfunction. We presented a novel promising treatment for the local delivery of ZnONPs in injured spinal cord based on skeletal muscle-derived hyaluronic acid (HA) hydrogel (ZnONPs-Gel). The implantation of ZnONPs-Gel effectively recovered the hindlimb motor function in SCI mice via regulating the focus microenvironment and suppressing inflammation and ROS. This study developed an innovative strategy for the local delivery of ZnONPs for SCI treatment

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RESULTS AND DISCUSSION

CONCLUSION

ETHICS STATEMENT