LAUSR

Osteochondral defect (OCD) regeneration remains challenging because of the hierarchy of the native tissue including both the articular cartilage and the subchondral bone. Constructing an osteochondral scaffold with biomimetic composition, structure and biological functionality is the key to achieve its high-quality repair. In the present study, we developed an injectable and 3D printable bilayered osteochondral hydrogel (BLH) based on compositional gradient of methacrylated sodium alginate (SAMA), gelatin methacryloyl (GelMA) and β-tricalcium phosphate (β-TCP), as well as the biochemical gradient of kartogenin (KGN) in the two well-integrated zones of chondral layer hydrogel (CLH) and osseous layer hydrogel (OLH). In vitro and subcutaneous in vivo evaluations revealed that apart from the chondrogenesis of the embedded bone mesenchymal stem cells (BMSCs) induced by CLH with a high concentration of KGN, a low concentration of KGN with β-TCP in the OLH synergistically achieved superior osteogenic differentiation by endochondral ossification, instead of the intramembranous ossification using OLH with only β-TCP. The biomimetic construct leveraging KGN as the only biochemical inducer could facilitate cartilage and subchondral bone restoration in the in vivo osteochondral defect. This one-stone-two-birds strategy opens up a new facile approach for OCD regeneration by exploiting the biological functions of the bioactive drug molecule KGN. This article is protected by copyright. All rights reserved.