A drug-loaded nano chitosan/hyaluronic acid hydrogel system as a cartilage tissue engineering scaffold for drug delivery

Cartilage lesions, especially osteoarthritis (OA), usually arise from aging, trauma, or obesity and require medical intervention due to the damaged site's inflammation and the cartilage tissue's poor self-healing capacity. This study aimed to prepare a drug-loaded nanoparticle hydrogel system with anti-inflammatory and chondroprotective effects to treat OA. First, hyaluronic acid (HA) was oxidized to create aldehyde functional groups and then cross-linked with adipic acid dihydrazide (ADH) to form a hydrogel. Next, chitosan nanoparticles (CS NPs) loaded with an anti-inflammatory molecule (fisetin) and or a chondrogenic and chondroprotective agent (kartogenin) were incorporated into the hyaluronan hydrogel to improve the release profile of the drug and increase its retention time in the joint cavity. Incorporating drug-loaded NPs into the hyaluronan hydrogel provided the hydrogel with controlled release features and improved properties. In addition, the real-time PCR (polymerase chain reaction) results showed that the hyaluronan hydrogel containing both drug-loaded NPs performed better than either constituent alone on an in vitro model of OA. Finally, based on the results of in vitro evaluation, this drug-loaded nanoparticle hydrogel system can be a promising technique for treating OA by rapidly suppressing inflammation and supporting cartilage regeneration and requires further investigation in an animal model of OA. Meanwhile, this study investigated, for the first time, the effect of the simultaneous use of fisetin and kartogenin together with a nano CS/HA hydrogel system to treat OA.