Hierarchical 3D-printed scaffolds for osteochondral regeneration: From biomimetic design to functional integration

Abstract

Osteochondral defects, characterized by the structural and functional disruption of articular cartilage and subchondral bone, present significant clinical challenges due to the tissue’s limited intrinsic regenerative capacity. Scaffold-based tissue engineering has paved the way for osteochondral defect treatment; however, fully restoring the complex structure and composition of native osteochondral tissue remains challenging. Recent advances in three-dimensional (3D) printing have enabled the fabrication of layered, anisotropic scaffolds designed to biomimetically recapitulate the native tissue’s zonal properties through precise hierarchical design. High-resolution fabrication techniques facilitate the construction of delicate microarchitectures, while advanced bioprinting methods allow for the incorporation of bioactive factors and cells into the scaffold matrix. This review emphasizes the following four scaffold design paradigms: composite gradients, microarchitectural patterning, biochemical gradients, and cellular heterogeneity. Moreover, key properties of multilayered scaffolds are discussed, including mechanical performance, interfacial strength, and degradation behavior. In addition, several obstacles associated with the in vivo scaffold application are discussed, providing insights to guide future clinical translation in osteochondral defects treatment.