Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti ‐Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus

Degradation of the HAS2@DexP-Gel results in the release of the HAS2 lentivirus and DexP molecules. Transfected FLS shows increased endogenous HA production facilitated by the HAS2 lentivirus. Furthermore, DexP molecules inhibit M1 macrophages through modulation of the PI3K/AKT/mTOR/HIF-1 α pathway. Synergistic effects of HAS2@DexP-Gel collectively suppress synovitis and delay cartilage degeneration. AbstractOsteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra-articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel-based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus-encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP-Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra-articular injection of HAS2@DexP-Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP-Gel reduces subchondral bone resorption in the anterior cruciate ligament transection-induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP-Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP-Gel a...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research