Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy

Linjie Chen, Ke Peng,He Huang, Zehua Gong, Jinyi Huang, Abdihafid Mohamud Mohamed,Qizhu Chen,Wan Ting Sow, Liting Guo,Kenny Yat Hong Kwan, Bin Li,Moonis Ali Khan, Pooyan Makvnadi,Morgan Jones,Shuying Shen,Xiangyang Wang,Chao Ma,Huaqiong Li,Aimin Wu

Advanced Functional Materials(2024)

引用 0|浏览1
暂无评分
摘要
AbstractThe treatment of intervertebral disc degeneration (IVDD) using bone marrow mesenchymal stem cell‐derived exosomes has shown success in alleviating inflammation and restoring the extracellular matrix (ECM), however, challenges persist due to the deficiency in mechanical support and controlled release. Herein, a carbon‐carbon double bond modified keratin (KeMA) is synthesized by 2‐isocyanatoethyl modification for exosomes wrapping. This injectable KeMA hydrogel, initiated by a biocompatible glucose/ glucose oxidase/ horse radish peroxidase enzymatic cascade reaction with acetylacetone and N‐vinylpyrrolidone, displayed rapid gelation, resembling nucleus pulposus (NP) elasticity, and excellent cytocompatibility. In vitro studies showcased that the exosomes‐loaded KeMA hydrogel (Exo@KeMA) enhanced exosome release kinetics, suppressed inflammation, fostered extracellular matrix (ECM) regeneration, and reinstated NP biomechanics. RNA‐seq analysis indicated Exo@KeMA's effects involved PI3K‐Akt signaling for matrix regeneration and NF‐κB signaling inhibition for anti‐inflammation. In vivo IVDD rat models demonstrated Exo@KeMA attenuated inflammation, maintained NP water content, preserved disc height, and promoted structural regeneration. This research introduces an injectable KeMA hydrogel as a promising therapy for IVDD, by facilitating biomechanics restoration, anti‐inflammatory response, and ECM regeneration.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要