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.

Arbutin-Modified Microspheres Prevent Osteoarthritis Progression by Mobilizing Local Anti-Inflammatory and Antioxidant Responses

“…Due to the negatively charged surface of articular cartilage [42], cationic Liposomes selectively accumulate on cartilage without diffusing into the synovial tissues. Furthermore, the positively charged Liposome penetrates deep into the cartilage matrix and controllably releases ARB to regulate the cartilaginous in ammation-redox balance [43]. Additionally, our in vitro assays indicated a superb cell-microsphere complex, in which cells proliferated stably and produced abundant levels of cartilage-related matrix components.…”

Transporting Hydrogel via Chinese Acupuncture Needles for Lesion Positioning Therapy

“…The advantage of lesion positioning therapy is that it can precisely localize drugs to the lesion and produce an enrichment effect, which can greatly improve drug efficacy and significantly reduce the side effects caused by treatment. [ 1 , 2 , 3 , 4 ] At present, lesion positioning treatment of various diseases has been achieved through the application of functional biological materials, such as hydrogel microspheres [ 5 ] and electrospinning. [ 6 ] However, the physical barrier of the physiological structure of some tissues or organs (such as intervertebral discs [ 7 ] and cartilage [ 8 ] ) greatly hinders the implementation of lesion positioning therapy.…”

Microcarriers in application for cartilage tissue engineering: Recent progress and challenges

“…Feng et al introduced an adhesive hydrogel MC characterized with positively charged nanostructure that allowed it to penetrate deeply into the cartilage with charge guidance ( Fig. 6 B) [ 318 ]. Articular cartilage lesions are often accompanied by the appearance of an acidic environment.…”

“…2019, Wiley Periodicals, Inc. B: Schematic illustration of charge-guided micro/nano-hydrogel MCs with ROS-responsive drug release for treating OA. Reproduced with permission [ 318 ]. 2021, Wiley-VCH GmbH.…”