Compartmentalized Dual-Drug Injectable Hydrogel for Anti-Inflammatory Activity and Osteoarthritic Cartilage Repair

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Osteoarthritis Therapeutics

Background:

• Cartilage's limited healing capacity and joint inflammation pose challenges for osteoarthritis (OA) treatment.
• Minimally invasive, multifunctional biomaterials are needed to modulate the joint microenvironment in OA.

Purpose of the Study:

• To develop a compartmentalized dual-drug injectable hydrogel (DD gel) for simultaneous inflammation control and chondroprotection in OA.
• To create a biomaterial that addresses the complex pathological features of osteoarthritis.

Main Methods:

• Designed a crosslinker-free hydrogel matrix with two compartments: celecoxib for immediate anti-inflammatory effects and chondroitin sulfate-loaded GelMA microspheres for sustained chondroprotection.
• Evaluated hydrogel properties including injectability, mechanical strength, and shear-thinning behavior.
• Assessed the DD gel's effects on chondrocyte function, inflammation, oxidative stress, and extracellular matrix (ECM) degradation in vitro and cartilage regeneration in vivo using a rabbit model.

Main Results:

• The DD gel exhibited rapid physiological gelation, good injectability, and mechanical properties.
• In vitro studies showed the DD gel enhanced chondrocyte proliferation, migration, and ECM synthesis while reducing inflammation and oxidative stress.
• In vivo implantation in a rabbit OA model promoted significant cartilage regeneration, nearing native tissue quality by 8 weeks.

Conclusions:

• The developed DD gel is a promising injectable system for combinatorial osteoarthritis therapy.
• This multifunctional biomaterial effectively controls inflammation and promotes cartilage repair, addressing key challenges in OA treatment.