Maintaining the Cartilage Phenotype of Late-Passage Chondrocytes Using Salidroside, TGF-β, and Sulfated Alginate for Cartilage Tissue Engineering Applications

Int J Mol Sci. 2024 Dec 19;25(24):13623. doi: 10.3390/ijms252413623.

Abstract

The limited self-repair capacity of cartilage due to its avascular and aneural nature leads to minimal regenerative ability. Autologous chondrocyte transplantation (ACT) is a popular treatment for cartilage defects but faces challenges due to chondrocyte dedifferentiation in later passages, which results in undesirable fibroblastic phenotypes. A promising treatment for cartilage injuries and diseases involves tissue engineering using cells (e.g., chondrocytes), scaffolds (e.g., Alginate Sulfate (AlgSulf)), and biochemical signals (e.g., Salidroside and TGF-β). This study focuses on investigating the effects of AlgSulf scaffolds with varying degrees of sulfation, Salidroside, and TGF-β on the proliferation, viability, and phenotype maintenance of chondrocytes. The findings demonstrate that AlgSulf films with a degree of sulfation (DS) = 2, treated with a combination of Salidroside and TGF-β, significantly enhanced chondrocyte proliferation (p < 0.001 and p < 0.0001 in P2 and P4, respectively), preserved round cell morphology, and maintained cartilage-specific gene expression (Col2, Aggrecans, and SOX9) while downregulating fibroblastic markers (Col1, MMP13, IL-1β, and IL-6). Our findings suggest the potential of this combination for enhancing cartilage regeneration in tissue engineering applications.

Keywords: Salidroside; TGF-β; alginate sulfate; cartilage; chondrocytes; tissue engineering.

MeSH terms

  • Alginates* / chemistry
  • Alginates* / pharmacology
  • Animals
  • Cartilage / cytology
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes* / cytology
  • Chondrocytes* / drug effects
  • Chondrocytes* / metabolism
  • Glucosides* / pharmacology
  • Phenols* / pharmacology
  • Phenotype*
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Sulfates / metabolism
  • Tissue Engineering* / methods
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta* / metabolism
  • Transforming Growth Factor beta* / pharmacology

Substances

  • rhodioloside
  • Alginates
  • Phenols
  • Glucosides
  • Transforming Growth Factor beta
  • SOX9 Transcription Factor
  • Sulfates