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

Lack of intrinsic healing potential in cartilage, accompanied by accelerated inflammation and oxidative stress, creates a major clinical challenge for effective treatment of osteoarthritis (OA). This highlights the need for the development of minimally invasive, multifunctional biomaterials capable of tuning the degenerative joint microenvironment. Herein, we designed a compartmentalized dual-drug injectable hydrogel (DD gel) matrix offering rapid inflammation control and sustained chondroprotective function to address the multifaceted challenges of OA. The hydrogel incorporating celecoxib acts as a primary compartment to attain an immediate anti-inflammatory response, whereas the chondroitin sulfate encapsulated GelMA microspheres act as a secondary compartment to facilitate chondroprotection and joint homeostasis. Moreover, the simple and crosslinker-free technique offers rapid gelation at physiological temperature, ensuring good injectability, mechanical strength, and shear-thinning properties. Further, the DD gel significantly improves chondrocyte proliferation, migration, and extracellular matrix (ECM) synthesis while effectively alleviating LPS-induced inflammation, oxidative stress, and ECM degradation. Additionally, in vivo implantation of DD gel stimulates the regeneration of cartilage tissue in a rabbit full-thickness cartilage defect model up to 8 weeks and achieves healing close to the native cartilage tissue. This single injectable system presents a promising approach for the combinatorial therapy for OA.