Charge‐Guided Micro/Nano‐Hydrogel Microsphere for Penetrating Cartilage Matrix

Abstract The dense structure and the high‐density negative charge of the cartilage matrix impede drug penetration into the cartilage. Effectively breaking through these barriers and transporting target drugs to the cartilage is currently difficult. Herein, an adhesive hydrogel microsphere characterized by its positively charged nanosized secondary structure that allows it to penetrate deep into the cartilage through charge guidance is introduced as an efficient drug delivery system for cartilage adhesion, cartilage matrix penetration, and chondrocytes targeting and solves the problem of drug‐penetration impedance due to cartilage. The dopamine‐modified structure on the surface of the microspheres can attach the microspheres onto the cartilage surface, while the charge‐guided secondary structure can carry drugs to penetrate the cartilage matrix, release drugs under reactive oxygen species stimulation, act on chondrocytes. The experiments show that the injectable microspheres successfully deliver antioxidants to chondrocytes in osteoarthritis environments. The apoptosis rate of chondrocytes under oxidative stress decreases from 38.36 ± 5.48% to 12.86 ± 4.27%, which is significantly better than that in the direct drug treatment group (28.43 ± 5.87%). The micro/nano‐hydrogel microsphere effectively penetrates the cartilage matrix and releases the drug in ROS response, realizing the improvement of drug utilization and efficacy and thereby demonstrating the efficient delivery of cartilage drugs.