Dual-dynamic-bond cross-linked injectable hydrogel of multifunction for intervertebral disc degeneration therapy

用于治疗椎间盘退变的多功能双动态交联可注射水凝胶

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作者:Linjun Yang #, Congcong Yu #, Xuhui Fan, Tianni Zeng, Wentao Yang, Jiechao Xia, Jianle Wang, Litao Yao, Chuan Hu, Yang Jin, Yutao Zhu, Jiaxin Chen, Zhijun Hu

Abstract

Developing smart hydrogels with integrated and suitable properties to treat intervertebral disc degeneration (IVDD) by minimally invasive injection is of high desire in clinical application and still an ongoing challenge. In this work, an extraordinary injectable hydrogel PBNPs@OBG (Prussian blue nanoparticles@oxidized hyaluronic acid/borax/gelatin) with promising antibacterial, antioxidation, rapid gelation, and self-healing characteristics was designed via dual-dynamic-bond cross-linking among the oxidized hyaluronic acid (OHA), borax, and gelatin. The mechanical performance of the hydrogel was studied by dynamic mechanical analysis. Meanwhile, the swelling ratio and degradation level of the hydrogel was explored. Benefiting from its remarkable mechanical properties, sufficient tissue adhesiveness, and ideal shape-adaptability, the injectable PBNPs containing hydrogel was explored for IVDD therapy. Astoundingly, the as-fabricated hydrogel was able to alleviate H2O2-induced excessive ROS against oxidative stress trauma of nucleus pulposus, which was further revealed by theoretical calculations. Rat IVDD model was next established to estimate therapeutic effect of this PBNPs@OBG hydrogel for IVDD treatment in vivo. On the whole, combination of the smart multifunctional hydrogel and nanotechnology-mediated antioxidant therapy can serve as a fire-new general type of therapeutic strategy for IVDD and other oxidative stress-related diseases.

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