Recent advances in injectable hydrogels for osteoarthritis treatments

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone alterations, poses significant challenges due to its high prevalence and associated disability. Injectable hydrogels have emerged as promising candidates for OA treatment due to their ability to deliver bioactive molecules directly to the affected joint, enhancing local efficacy while minimizing systemic side effects. This review focuses on recent advances in injectable hydrogels for OA treatment, emphasizing their structural design, functional properties, and therapeutic applications. We further discuss the advantages and limitations of natural, synthetic, and composite hydrogels, as well as innovative cross-linking strategies and stimuli-responsive behaviors. Thermosensitive, pH-responsive, enzyme-responsive, and multi-responsive hydrogels are highlighted for their potential to achieve intelligent drug delivery, inhibit cartilage degradation, and reduce inflammation. Overall, injectable hydrogels hold great promise for OA treatment and become an effective therapeutic option with further research and innovation.

Keywords: biocompatibility; injectable hydrogels; osteoarthritis; stimuli-responsive hydrogels; therapeutic hydrogels.

FIGURE 1

Overview of design strategies of Injectable hydrogels for OA treatment.

FIGURE 2

VOS viewer map of injectable hydrogels for OA treatment.

FIGURE 3

Schematic illustrations of thermosensitive hydrogel systems for treating OA through controlled release of therapeutic agents. (a) P-HA releases rapamycin at 37°C, polarizing macrophages to reduce OA inflammation (Chen et al., 2023). (b) Pluronic F-127/HA delivers drugs, easing OA via anti-inflammation (Zhang J. et al., 2024). (c) Chitosan gel with Dex-DSLip/Cro targets RA macrophages, lowering ROS (Liu H. et al., 2024). (d) Ozone-rich gel releases D-mannose, inhibiting MMP13 to protect OA cartilage (Wu H. et al., 2024).

FIGURE 4

pH-responsive hydrogel systems for OA treatment, illustrating stimuli-triggered drug release and therapeutic mechanisms. (a) HA-PRP hydrogel releases BSA-BM nanoparticles under acidic OA conditions via Schiff base cleavage, scavenging ROS to reduce inflammation (Jia M. et al., 2024). (b) IA-ZIF-8@HMs microspheres respond to OA’s acidity, releasing IA to inhibit oxidative stress and inflammatory factors in chondrocytes (Yu et al., 2023). (c) MXenzyme-based hydrogel intelligently releases metformin in acidic environments, scavenging ROS to protect chondrocyte mitochondria (Zhang Z. et al., 2024).

FIGURE 5

Enzyme-responsive hydrogel systems for targeted OA therapy, showing MMP-triggered drug release and cartilage repair. (a) Bilayer ChsMA + CLX@Lipo@GelMA microspheres: MMPs degrade GelMA, releasing CLX (anti-inflammatory) and ChsMA (cartilage repair) (Miao et al., 2024). (b) MMP13-responsive HA methacrylate microspheres degrade in high MMP13 environments, releasing celecoxib-loaded liposomes for precise anti-inflammation (Xiang et al., 2024).

FIGURE 6

Multi-responsive hydrogel systems for OA, integrating temperature, pH, and ROS responsiveness to enhance therapeutic precision. (a) Thermo/enzyme-responsive hydrogel releases drugs via temperature rise and enzyme activation, boosting OA treatment efficacy (Sun et al., 2025). (b) pH/ROS-responsive APBA-SF/PVA hydrogel releases IFN-γ under OA’s acidity and high ROS, reducing inflammation (Lei et al., 2024). (c) Dual-responsive OSPPB hydrogel inhibits neurovascularization in OA via stimulus-triggered drug release (Qin et al., 2025). (d) ZIF-8-based hydrogel responds to pH/ROS, releasing quercetin to remodel OA’s microenvironment and promote repair (Salama et al., 2025).