Injectable pathological microenvironment-responsive anti-inflammatory hydrogels for ameliorating intervertebral disc degeneration

Liu，Lei1; Wang，Wantao1,2,3; Huang，Lin1; Xian，Yiwen1; Ma，Wenzheng1,2,3; Fan，Jinghao1; Li，Yixi1; Liu，Hongmei1; Zheng，Zhaomin2,3; Wu，Decheng1

2024-04-01

10.1016/j.biomaterials.2024.122509

Biomaterials   影响因子和分区

0142-9612

1878-5905

Chronic local inflammation and resulting cellular dysfunction of nucleus pulposus (NP) cells are important pathogenic factors of intervertebral disc degeneration (IDD). Injectable pathological microenvironment-responsive hydrogels hold significant potential for treating IDD by adapting to dynamic microenvironment of IDD. Herein, we proposed an injectable gelatin-based hydrogel drug delivery system that could respond to the pathological microenvironment of IDD for controlled release of anti-inflammatory drug to promote degenerative NP repair. The hydrogel system was prepared by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with the naturally extracted anti-inflammatory drug epigallocatechin-3-gallate (EGCG) through dynamic boronic esters. The hydrogel exhibited excellent degradability, injectability, antioxidant properties, anti-inflammatory effects, and biocompatibility. It also displayed responsive-release of EGCG under high reactive oxygen species (ROS) levels and acidic conditions. The hydrogel demonstrated remarkable cytoprotective effects on NP cells in both hyperactive ROS environments and inflammatory cytokine-overexpressed environments in vitro. In vivo studies revealed that the hydrogel injected in situ could effectively ameliorate the intervertebral disc degeneration by maintaining the disc height and NP tissue structure in a rat IDD model. The hydrogel system exhibited excellent biocompatibility and responsive-release of diol-containing drugs in pathological microenvironments, indicating its potential application as a drug delivery platform.

Gelatin hydrogel Inflammatory regulation Intervertebral disc degeneration repair Minimally invasive injection Responsive release

SCI ; EI

英语

第一 ; 通讯

MATERIALS SCIENCE

2-s2.0-85186263685

Scopus

1.Guangdong Provincial Key Laboratory of Advanced Biomaterials,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China
2.Department of Spine Surgery,The First Affiliated Hospital,Sun Yat-Sen University,Guangzhou,510080,China
3.Pain Research Center,Sun Yat-Sen University,Guangzhou,510080,China

Liu，Lei,Wang，Wantao,Huang，Lin,et al. Injectable pathological microenvironment-responsive anti-inflammatory hydrogels for ameliorating intervertebral disc degeneration[J]. Biomaterials,2024,306.

Liu，Lei.,Wang，Wantao.,Huang，Lin.,Xian，Yiwen.,Ma，Wenzheng.,...&Wu，Decheng.(2024).Injectable pathological microenvironment-responsive anti-inflammatory hydrogels for ameliorating intervertebral disc degeneration.Biomaterials,306.

Liu，Lei,et al."Injectable pathological microenvironment-responsive anti-inflammatory hydrogels for ameliorating intervertebral disc degeneration".Biomaterials 306(2024).