Sustained gene delivery from inflammation-responsive anti-inflammatory hydrogels promotes extracellular matrix metabolism balance in degenerative nucleus pulposus. (1st May 2022)

• Record Type: Journal Article
• Authors: Wang, Yu; Deng, Mingyan; Wu, Ye; Hu, Cheng; Zhang, Bo; Guo, Chuan; Song, Haoyang; Kong, Qingquan; Wang, Yunbing
• Is Part Of: Composites. Number 236(2022)
• Publication Date: 2022-05-01
• Subjects: Inflammation-responsive hydrogel -- Nucleus pulposus -- Antagomir-21 -- Curcumin -- Sustained release; Composite materials -- Periodicals; Materials science -- Periodicals; Composite materials; Periodicals; Electronic journals; 620.118
• DOI: 10.1016/j.compositesb.2022.109806
• Languages: English
• ISSNs: 1359-8368

Abstract

Abstract: The progression of intervertebral disc degeneration (IDD) is characterized by an initial chronic local inflammatory response and ultimately leads to unbalanced anabolic/catabolic activity within the nucleus pulposus (NP). Injectable inflammation-responsive hydrogels have great potential in treating IDD through on-demand local drug delivery. Here, we designed an injectable inflammation-responsive gelatin-based hydrogel for local and sustained delivery of the naturally extracted anti-inflammatory curcumin and a cholesterol-modified miRNA-21 inhibitor (Antagomir-21) to treat IDD. We successfully demonstrated the robust biocompatibility and ideal inflammation-responsive and on-demand drug release properties of hydrogels, as well as the great potential of IDD regeneration. This work proposes the novel inflammation-responsive hydrogel-based curcumin and miRNA delivery systems for the treatment of IDD. Graphical abstract: Image 1 Highlights: The hydrogel exhibited sensitve inflammation-responsive property (low pH and high ROS). The on-demand delivered curcumin played strong anti-inflammatory role. Cholesterol-modified miRNA would sustained release owing to the host-guest interactions with CD. Antagomir-21 persistently promoted ECM regeneration of NPCs by promoting autophagy activation. The anti-inflammation and ECM regeneration behavior of hydrogel positively promoted IDD repair.