3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration.

Cartilage injury is extremely common and leads to joint dysfunction. Existing joint prostheses do not remodel with host joint tissue. However, developing large-scale biomimetic anisotropic constructs mimicking native cartilage with structural integrity is challenging. In the present study, we describe anisotropic cartilage regeneration by three-dimensional (3D) bioprinting dual-factor releasing and gradient-structured constructs. Dual-factor releasing mesenchymal stem cell (MSC)-laden hydrogels were used for anisotropic chondrogenic differentiation. Together with physically gradient synthetic biodegradable polymers that impart mechanical strength, the 3D bioprinted anisotropic cartilage constructs demonstrated whole-layer integrity, lubrication of superficial layers, and nutrient supply in deep layers. Evaluation of the cartilage tissue in vitro and in vivo showed tissue maturation and organization that may be sufficient for translation to patients. In conclusion, one-step 3D bioprinted dual-factor releasing and gradient-structured constructs were generated for anisotropic cartilage regeneration, integrating the feasibility of MSC- and 3D bioprinting-based therapy for injured or degenerative joints.