3D vertical extrusion cryo(bio)printing strategies for guiding endogenous osteochondral regeneration

Osteochondral defect is a common orthopedic disease that can lead to more serious joint degeneration. Although the 3D extrusion bioprinting method is a promising tool for osteochondral repair, it has limitations in creating anisotropic tissues, such as the vertically aligned microstructure of the knee joint. Here, we developed a versatile strategy, 3D vertical extrusion cryo(bio)printing, which allows convenient 3D bioprinting and simultaneous generation of anisotropic microstructures. Using this method, we fabricated a bionic scaffold with vertical, uniform, and continuous microchannels that mimic the normal bone trabecula alignment of the knee joint. To repair osteochondral defects, we printed a bi-layer osteochondral scaffold (3 mm in height), consisting of an osteogenesis-induced layer (2 mm in height) and a chondrogenesis-induced layer (1 mm in height). The cryoprinted bioink for the osteogenesis-induced part was prepared by mixing a 5% (m/v) GelMA solution, 1% (m/v) hydroxyapatite (HA), and microspheroids constructed from GelMA with osteogenic peptides. The bioink for the chondrogenesis-induced layer consisted of 5% (m/v) GelMA and microspheroids constructed from GelMA with chondrogenic peptides. In vitro, the osteochondral scaffold guided BMSC migration into the vertical microchannels, and the different peptides induced osteogenic and chondrogenic differentiation of BMSCs. In vivo, the 3D vertical extrusion cryo(bio)printed scaffold guided endogenous osteochondral regeneration. These results may inspire the development of innovative materials for not only osteochondral defect repair but also various other anisotropic tissue engineering and bio-implantation applications.

Gao Zhiqiang, a Ph.D. student at Tongji University, School of Medicine. My research focuses on fabricating bionic scaffolds and drug-loading nanoparticles.