Targeting Macrophages via Ultrasonic Contrast Microspheres for Monitoring and Treatment of Knee Synovitis

Abstract The malignant cycle of synovitis considerably impacts the progression of osteoarthritis (OA). Therefore, the precise localization of synovitis, targeted disruption of the inflammatory cycle, and real‐time monitoring of its dynamics are crucial for the effective diagnosis and management of OA. Here, porous HAMA/GelMA microspheres are synthesized using microfluidic technology. Interleukin‐10 (IL‐10) nanobubbles, prepared via double emulsification, are grafted with folic acid (FA) via an amide reaction and subsequently impregnated and adsorbed onto the microspheres, thereby constructing an ultrasonic contrast microsphere system. This system facilitates not only ultrasonic imaging for accurate localization of synovitis but also the targeted and controlled delivery of IL‐10 under ultrasound conditions. In vitro, under ultrasound intensities of 0, 0.5, and 1.5 W, the system effectively releases IL‐10 at the rates of 19.95%, 30.95%, and 40.67%, respectively. In vivo, the biodegradability of the system facilitates real‐time tracking and monitoring of synovitis for at least 14 days. In summary, ultrasonic contrast microspheres enable precise localization and real‐time monitoring of synovitis. Under ultrasound conditions, these microspheres enable targeted and controlled drug delivery, effectively disrupting vicious inflammatory cycles. This strategy pioneers new pathways for the management and precise treatment of OA.