Curcumin-Loaded GelMA Microspheres Alleviate Osteoarthritis: Transcriptomic Evidence for Immune Microenvironment...

Area of Science:

• Biomaterials Science
• Immunology
• Rheumatology

Background:

• Osteoarthritis (OA) pathogenesis involves joint inflammation and immune cell imbalance.
• Curcumin (Cur) has therapeutic potential but suffers from poor solubility and short half-life.
• Developing effective drug delivery systems is crucial for OA treatment.

Purpose of the Study:

• To develop injectable curcumin-loaded GelMA microspheres (Cur-MS) for sustained local delivery.
• To evaluate the therapeutic efficacy of Cur-MS in preclinical OA models.
• To investigate the impact of Cur-MS on chondrocytes, cartilage, and the joint immune microenvironment.

Main Methods:

• Fabrication and characterization of Cur-MS for size, biocompatibility, and drug release.
• In vitro assessment using IL-1β stimulated chondrocytes and cartilage organoids.
• In vivo evaluation in a monosodium iodoacetate (MIA)-induced rat OA model.
• Analysis of gene expression and inflammatory markers.
• Complementary analysis of public transcriptomic data (GSE114007).

Main Results:

• Cur-MS exhibited uniform size, good biocompatibility, and sustained curcumin release.
• In vitro, Cur-MS reduced chondrocyte apoptosis, oxidative stress, and hypertrophy, while restoring matrix synthesis and downregulating MMP13.
• In vivo, Cur-MS alleviated OA symptoms, reduced joint inflammation (macrophages, IL-6, TNF-α), and improved cartilage markers.
• Transcriptomic analysis supported the modulation of key OA-related genes (MMP13, SOX9).

Conclusions:

• Cur-MS provides effective, localized, and sustained delivery of curcumin for OA treatment.
• The microspheres protect chondrocytes, restore extracellular matrix homeostasis, and modulate the joint immune response.
• Cur-MS represents a promising therapeutic strategy for managing osteoarthritis progression.