Cartilage injury is a very common joint disease, andcartilagerepair is a great challenge in clinical treatment due to the specificstructure of cartilage tissue and its microenvironment invivo. The injectable self-healing hydrogel is a very promisingcandidate as a cartilage repair material because of its special networkstructure, high water retention and self-healing properties. In thiswork, a self-healing hydrogel cross-linked by host-guest interactionbetween cyclodextrin and cholic acid was developed. The host materialwas composed of & beta;-cyclodextrin and 2-hydroxyethyl methacrylate-modifiedpoly(l-glutamic acid) (P(LGA-co-GM-co-GC)), while the guest material was chitosan modifiedby cholic acid, glycidyl methacrylate, and (2,3-epoxypropyl)trimethylammoniumchloride (EPTAC) (QCSG-CA). The host-guest interaction self-healinghydrogels, named as HG hydrogels (HG gel), exhibited excellent injectabilityand self-healable property, and the self-healing efficiency was greaterthan 90%. Furthermore, in order to enhance the mechanical propertiesand slow down the degradation of the HG gel in vivo, the second network was constructed by photo-cross-linking in situ. Biocompatibility tests showed that the enhancedmulti-interaction hydrogel (MI gel) was extremely suitable for cartilagetissue engineering both in vitro and in vivo. In addition, the adipose derived stem cells (ASCs) in MI gel wereable to differentiate cartilage effectively in vitro in the presence of inducing agents. Subsequently, the MI gel withoutASCs was transplanted into rat cartilage defects in vivo for the regeneration of cartilage. After 3 months postimplantation,new cartilage tissue was successfully regenerated in a rat cartilagedefect. All results indicated that the injectable self-healing host-guesthydrogels have important potential applications in cartilage injuryrepair.