Bioinks for engineering gradient-based osteochondral and meniscal tissue substitutes: a review

Gradient tissues are anisotropic structure with gradual transition in structural and biological properties. The gradient in structural, mechanical and biochemical properties of osteochondral and meniscal tissues play a major role in defining tissue functions. Designing tissue substitutes that replicate these gradient properties is crucial to facilitate regeneration of tissue functions following injuries. Advanced manufacturing technologies such as 3D bioprinting hold great potentials for recreating gradient nature of tissues through using zone-specific bioinks and layer-by-layer deposition of spatially defined biomaterials, cell types and bioactive cues. This review highlighted the gradients in osteochondral and meniscal tissues in detail, elaborated on individual components of the bioink, and reviewed recent advancements in 3D gradient-based osteochondral and meniscal tissue substitutes. Finally, key challenges of the field and future perspectives for developing gradient-based tissue substitutes were discussed. The insights from these advances can broaden the possibilities for engineering gradient tissues.