Self-disintegrating electrospun short fibers as intra-articular drug depots for gouty arthritis

Effective intra-articular therapy requires injectable depots that persist in the synovial space and modulate local inflammatory and oxidative microenvironments. Here, we developed a high-aspect-ratio short-fiber platform based on acid-labile acetalated dextran (AcDEX) for sustained intra-articular drug delivery. Continuous AcDEX fibermats electrospun from low-molecular-weight (10 kDa) dextran self-disintegrated within seconds into injectable short fibers (average aspect ratio ~ 30) upon mild agitation in aqueous media, enabling on-demand preparation without post-processing. Resveratrol (RES), a hydrophobic antioxidant and anti-inflammatory compound, was encapsulated into AcDEX by blend electrospinning. RES@AcDEX fibers remained chemically intact during disintegration and provided sustained, pH-accelerated RES release (pH 6.8 vs 7.4) together with prolonged intra-articular retention, as evidenced by joint-confined fluorescence detectable for up to 10 days after injection. Released RES scavenged reactive oxygen species (ROS) in a dose-dependent manner, reduced intracellular ROS in lipopolysaccharide (LPS)-stimulated macrophages, and modulated inflammatory macrophage phenotypes in vitro. In a gouty arthritis model, a single intra-articular injection of RES@AcDEX short fibers reduced swelling, improved gait performance, downregulated proinflammatory cytokines, and upregulated anti-inflammatory cytokines in periarticular tissues. Overall, self-disintegrating AcDEX short fibers offer a simple and tunable, shape-engineered intra-articular depot for local modulation of ROS and inflammation, with potential utility for gouty arthritis and other inflammatory joint disorders.