Microfluidic liposomes-anchored microgels as extended delivery platform for treatment of osteoarthritis

Immobilizing liposomes in the hydrogel matrix network has become an effective strategy to protect liposomes against rapid clearance in the body, thus facilitating their localized drug delivery in a controlled and sustained manner for a long period. However, the low efficiency of drug delivery and short joint retention time seriously weaken its therapeutic efficacy. Herein, an efficient delivery platform was designed to anchor liposomes by integrating them with photo-crosslinkable GelMA matrix, rapidly forming monodisperse GelMA@Lipo hybrid microgels under ultraviolet light using a one-step innovational microfluidics technology. The liposomes were firmly anchored within microgels by the physical network hindrance and non-covalent interaction. Due to the double impediment from the lipid membrane and the hydrogel matrix network, kartogenin (KGN) encapsulated in GelMA@Lipo microgel presented notable extended release kinetics. Compared with KGN-loaded liposomes (Lipo@KGN), KGN-loaded GelMA@Lipo microgels (GelMA@Lipo@KGN) could extend KGN release for over three weeks and remarkably promote chondrocyte differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Furthermore, the in vivo study demonstrated that GelMA@Lipo@KGN, with enhanced joint residence over five weeks, could effectively reduce osteophyte burden and prevent articular cartilage degeneration as well as subchondral bone changes when intraarticularly injected in a surgically induced rat osteoarthritis model. Collectively, GelMA@Lipo microgel, as an innovative extended delivery platform, holds tremendous potential for osteoarthritis treatment.