Engineering materials with transient gradients to repair the musculoskeletal interface

The human body possesses a remarkable capacity for self-repair. However, disease, aging, and injury often impair its ability to restore complex tissue architectures essential for full function. Regenerative medicine integrates principles of chemistry, biology, and engineering to enhance natural processes through the design of implants and scaffolds that support host tissue integration. The musculoskeletal system, comprising bone, muscle, tendon, and ligament, features a hierarchical hard-to-soft tissue interface. Although significant progress has been made in developing tissue-engineered constructs that mimic these natural architectures, achieving structural and compositional gradient remains a major clinical challenge. This review summarises current advances in the design of functional and responsive biomaterials, particularly those that recapitulate extracellular matrix gradients and growth factor dynamics. Emerging fabrication strategies for complex, self-organising scaffolds are examined, and key challenges and opportunities for translating these responsive materials into clinically viable regenerative therapies are highlighted.