2. Academic Validation
  3. Locally delivered modified citrus pectin - a galectin-3 inhibitor shows expected anti-inflammatory and unexpected regeneration-promoting effects on repair of articular cartilage defect

Locally delivered modified citrus pectin - a galectin-3 inhibitor shows expected anti-inflammatory and unexpected regeneration-promoting effects on repair of articular cartilage defect

  • Biomaterials. 2022 Dec;291:121870. doi: 10.1016/j.biomaterials.2022.121870.
Yiyun Zhang 1,  Danning Su 1,  Yimeng Wang 1,  Ziqiang Wang 1,  Ying Ren 1,  Rui Liu 1,  Bo Du 1,  Ruiping Duan 1,  Yanping Shi 2,  Lingrong Liu 1,  Xuemin Li 3,  Qiqing Zhang 4
Affiliations

Affiliations

  • 1 The Key Laboratory of Biomedical Material of Tianjin, Biomedical Barriers Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Biomedical Engineering, Tianjin, 300192, PR, China.
  • 2 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, PR, China.
  • 3 The Key Laboratory of Biomedical Material of Tianjin, Biomedical Barriers Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Biomedical Engineering, Tianjin, 300192, PR, China. Electronic address: [email protected].
  • 4 The Key Laboratory of Biomedical Material of Tianjin, Biomedical Barriers Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Biomedical Engineering, Tianjin, 300192, PR, China. Electronic address: [email protected].
PMID: 36343609 DOI: 10.1016/j.biomaterials.2022.121870
Abstract

Treating the concomitant inflammation in the process of injury and repair, and simultaneously promoting cartilage regeneration is very important for the repair of articular cartilage (AC) defects. Nevertheless, this remains a massive challenge. To address this issue, a collagen membrane-based modified citrus pectin (MCP) delivery system (MCP-C) was developed in this study by targeting Galectin-3 (Gal-3), an upstream proinflammatory factor. As expected, MCP shows anti-inflammatory effects; it downregulates the expressions of IL-1β, MMP13, Gal-3, and COL1A2, inhibits the degenerative effects of Gal-3 on chondrocytes in vitro, and protects chondrocytes from degeneration and death in vivo. Unexpectedly, MCP promotes the proliferation of chondrocytes, upregulates the expression of COL2A1 and SOX9 in the chondrocytes in vitro, and enhances the repair of AC defect in rabbit knee, especially MCP500-C with a complete release of the loading amount of approximately 500 μg/cm2 in a day. Mechanistically, MCP upregulates the expressions of multiple endogenous growth factors for chondrogenesis via the transcriptome sequencing of MCP-treated chondrocytes, and downregulates the expressions of various inflammatory factors. These findings demonstrate that locally delivered MCP can simultaneously modulate both regenerative and inflammatory responses, and can enhance the repair of AC defects.

Keywords

Articular cartilage; Collagen; Galectin-3; Local delivery; Modified citrus pectin (MCP).

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