• Hyaluronan Hydrogel Reinforced with Drug-Loaded Chitosan Nanoparticles for Cartilage Tissue Regeneration
  • Zahra Nabizadeh,1,* Davood Nasrabadi,2
    1. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran


  • Introduction: Cartilage lesions, especially osteoarthritis, usually arise from aging, trauma, or obesity and require medical intervention due to the poor self-healing capacity of articular cartilage. Two major challenges need to be addressed in the repair of cartilage tissue. The first is the regeneration of articular cartilage in an active inflammatory environment. The second is to fill the space of the defect with tissue that has the same mechanical properties as articular cartilage tissue.
  • Methods: This study selected chitosan and oxidized hyaluronic acid (oxi-HA) to synthesize nanoparticles and an injectable hydrogel. Chitosan nanoparticles were loaded with a small anti-inflammatory molecule (fisetin) and a chondrogenic and chondroprotective agent (kartogenin). Oxidized hyaluronic acid was cross-linked with adipic acid dihydrazide (ADH) to form an injectable hydrogel. Then, the different concentrations of chitosan nanoparticles were embedded in oxi-HA/ADH hydrogel to investigate their effect on mechanical properties, gelation time, and controlled release of drugs.
  • Results: The results showed that incorporating drug-loaded chitosan nanoparticles into the oxi-HA/ADH hydrogel improved its drug release and increased its mechanical properties. Real-time PCR results showed that the COL2A1 mRNA expression was significantly increased in the hydrogel containing both drug-loaded chitosan nanoparticles compared to others. In contrast, INOS, TNF-α, and MMP-13 expression was significantly reduced in this group compared to the other groups.
  • Conclusion: In conclusion, based on the results of this study, this injectable nanoparticle hydrogel system may be a promising technique for repairing damaged cartilage tissue by rapidly suppressing inflammation and supporting cartilage regeneration and requires further investigation in an animal model of OA.
  • Keywords: Chitosan Nanoparticles, Drug Delivery System, Cartilage Tissue Engineering