Scheme 1.

Lineage-specific multifunctional double-layer scaffolds accelerate the integrated regeneration of cartilage and subchondral bone. The upper layer is composed of an HA-based hydrogel loaded with starved BMSCs-Evs and sVEGF. By releasing starved BMSCs-Evs and sVEGF, the hydrogel can activate the activity of chondrocytes, promote the proliferation and biosynthesis of a small number of chondrocytes in the cartilage defect after in situ implantation, and reduce the cartilage hypertrophy, thus forming stable cartilage. The lower layer is composed of collagen-based hydrogel containing calcium and thrombin. By optimizing the structure of the gel and the content of thrombin, the blood in the bone marrow cavity can be quickly absorbed and solidified to form a haematoma after being implanted into the body to promote bone formation and prevent the blood vessels in the bone marrow cavity from invading the cartilage layer.