Building a Poly(amino acid)/Chitosan-Based Self-Healing Hydrogel via Host–Guest Interaction for Cartilage Regeneration

Abstract

Cartilage injury is a very common joint disease, and cartilage repair is a great challenge in clinical treatment due to the specific structure of cartilage tissue and its microenvironment <i>in vivo</i>. The injectable self-healing hydrogel is a very promising candidate as a cartilage repair material because of its special network structure, high water retention and self-healing properties. In this work, a self-healing hydrogel cross-linked by host-guest interaction between cyclodextrin and cholic acid was developed. The host material was composed of β-cyclodextrin and 2-hydroxyethyl methacrylate-modified poly(l-glutamic acid) (P(LGA-<i>co</i>-GM-<i>co</i>-GC)), while the guest material was chitosan modified by cholic acid, glycidyl methacrylate, and (2,3-epoxypropyl)trimethylammonium chloride (EPTAC) (QCSG-CA). The host-guest interaction self-healing hydrogels, named as HG hydrogels (HG gel), exhibited excellent injectability and self-healable property, and the self-healing efficiency was greater than 90%. Furthermore, in order to enhance the mechanical properties and slow down the degradation of the HG gel <i>in vivo</i>, the second network was constructed by photo-cross-linking <i>in situ</i>. Biocompatibility tests showed that the enhanced multi-interaction hydrogel (MI gel) was extremely suitable for cartilage tissue engineering both <i>in vitro</i> and <i>in vivo</i>. In addition, the adipose derived stem cells (ASCs) in MI gel were able to differentiate cartilage effectively <i>in vitro</i> in the presence of inducing agents. Subsequently, the MI gel without ASCs was transplanted into rat cartilage defects <i>in vivo</i> for the regeneration of cartilage. After 3 months postimplantation, new cartilage tissue was successfully regenerated in a rat cartilage defect. All results indicated that the injectable self-healing host-guest hydrogels have important potential applications in cartilage injury repair.