Customized triphasic cartilage composite scaffold simulating hypoxic microenvironment for osteochondral regeneration

The regeneration of the osteochondral complex in situ presents a significant challenge. The inherent hypoxic microenvironment of cartilage plays a critical role in facilitating osteochondral repair. The successful regeneration of the osteochondral complex necessitates the utilization of materials and structures that closely mimic its composition. In this study, carboxymethyl chitosan (CCS), oxidized hyaluronic acid (OHA), and tannic acid (Ta) were employed to fabricate an injectable and self-healing hydrogel (Ta@gel). The incorporation of Ta within the hydrogel network enables preferential oxidation, thereby creating an anoxic microenvironment within the hydrogel. Bone marrow-derived mesenchymal stem cells (BMSCs) were encapsulated within microspheres composed of methacrylic anhydride gelatin (GelMA). These microspheres were subsequently loaded into a Ta@gel. The resulting bionic hydrogel composite was then combined with a three-dimensional (3D) printed hydroxyapatite (HAp) scaffold coated with poly-l-lysine (PLL). This combination resulted in the formation of a bionic three-layer composite structure (HAp@PLL + Ta@gel + GelMA@BMSCs) that closely resembles the complex composition and structure of natural osteochondral complex. The efficacy of this customized triphasic composite scaffold in promoting osteochondral complex regeneration has been demonstrated in vitro and in vivo. Consequently, this study provided a new sight for inducing the in situ regeneration of cartilage.