A triphasic biomimetic BMSC-loaded scaffold for osteochondral integrated regeneration in rabbits and pigs

Osteochondral tissue involves cartilage, calcified cartilage and subchondral bone. These tissues differ significantly in chemical compositions, structures, mechanical properties and cellular compositions. Therefore, the repairing materials face different osteochondral tissue regeneration needs and rates. In this study, we fabricated an osteochondral tissue-inspired triphasic material, which was composed of a poly(lactide-co-glycolide) (PLGA) scaffold loaded with fibrin hydrogel, bone marrow stromal cells (BMSCs) and transforming growth factor-β1 (TGF-β1) for cartilage tissue, a bilayer poly(L-lactide-co-caprolactone) (PLCL)-fibrous membrane loaded with chondroitin sulfate and bioactive glass, respectively, for calcified cartilage, and a 3D-printed calcium silicate ceramic scaffold for subchondral bone. The triphasic scaffold was press-fitted into the osteochondral defects in rabbit (cylindrical defects with a diameter of 4 mm and a depth of 4 mm) and minipig knee joints (cylindrical defects with a diameter of 10 mm and a depth of 6 mm). The μ-CT and histological analysis showed that the triphasic scaffold was partly degraded, and significantly promoted the regeneration of hyaline cartilage after they were implanted in vivo. The superficial cartilage showed good recovery and uniformity. The calcified cartilage layer (CCL) fibrous membrane was in favor of a better cartilage regeneration morphology, a continuous cartilage structure and less fibrocartilage tissue formation. The bone tissue grew into the material, while the CCL membrane limited bone overgrowth. The newly generated osteochondral tissues were well integrated with the surrounding tissues too.