A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM.

Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.