Cell‐Free Bilayered Porous Scaffolds for Osteochondral Regeneration Fabricated by Continuous 3D‐Printing Using Nascent Physical Hydrogel as Ink

Abstract Cartilage is difficult to self‐repair and it is more challenging to repair an osteochondral defects concerning both cartilage and subchondral bone. Herein, it is hypothesized that a bilayered porous scaffold composed of a biomimetic gelatin hydrogel may, despite no external seeding cells, induce osteochondral regeneration in vivo after being implanted into mammal joints. This idea is confirmed based on the successful continuous 3D‐printing of the bilayered scaffolds combined with the sol‐gel transition of the aqueous solution of a gelatin derivative (physical gelation) and photocrosslinking of the gelatin methacryloyl (gelMA) macromonomers (chemical gelation). At the direct printing step, a nascent physical hydrogel is extruded, taking advantage of non‐Newtonian and thermoresponsive rheological properties of this 3D‐printing ink. In particular, a series of crosslinked gelMA (GelMA) and GelMA‐hydroxyapatite bilayered hydrogel scaffolds are fabricated to evaluate the influence of the spacing of 3D‐printed filaments on osteochondral regeneration in a rabbit model. The moderately spaced scaffolds output excellent regeneration of cartilage with cartilaginous lacunae and formation of subchondral bone. Thus, tricky rheological behaviors of soft matter can be employed to improve 3D‐printing, and the bilayered hybrid scaffold resulting from the continuous 3D‐printing is promising as a biomaterial to regenerate articular cartilage.