Abstract
The intricate hierarchical structure of musculoskeletal tissues, including bone and interface tissues, necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes. This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes. Building on the anatomical characteristics of bone and interfacial tissues, this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues, specifically focusing on methods used to construct compositional and structural gradients within the scaffolds. The latest applications of gradient scaffolds for the regeneration of bone, osteochondral, and tendon-to-bone interfaces are presented. Furthermore, the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed, as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.