In situ biomimetic lyotropic liquid crystal gel for full-thickness cartilage defect regeneration

There is a great challenge in regenerating cartilage defects, which usually involve absent bearing capacity and poor adaptation to joint movement, further exacerbating subchondral bone damage. Therefore, ideal tissue-engineering cartilage scaffolds should be endowed with biomimetic and sustained-release function for promoting long-term chondrogenesis while protecting subchondral bone. Herein, in situ self-assembling gel based on glyceryl monooleate (GMO)-hyaluronic acid (HA) composite lyotropic liquid crystal (HLC) was developed as the biomimetic scaffold to deliver kartogenin for long-term cartilage regeneration. Compared to the GMO based (LLC) gel, HLC gel with modified lattice structure exhibited improved rheological properties for better joint protection by increasing mechanical strength, elasticity and lubrication. Besides, HLC gel successfully prolonged drug release and retention in the joint cavity over 4 weeks to provide combined effect of kartogenin and HA for cartilage repair. Pharmacodynamic studies demonstrated that HLC gel was the most effective to promote chondrogenesis and protect subchondral bone, making the damaged bone tissue restored to normal in divergent features as evidenced by the MRI, Micro-CT and histological results. Therefore, the HLC gel with joint protection and controlled drug release can serve as a firm scaffold for providing long-term cartilage repair.