Abstract
The musculoskeletal system works at a very advanced level of synchrony, where all the physiological movements of the body are systematically performed through well-organized actions of bone in conjunction with all the other musculoskeletal soft tissues, such as ligaments, tendons, muscles, and cartilage through tissue-tissue interfaces. Interfaces are structurally and compositionally complex, consisting of gradients of extracellular matrix components and cell phenotypes as well as biochemical compositions and are important in mediating load transfer between the distinct orthopedic tissues during body movement. When an injury occurs at interface, it must be re-established to restore its function and stability. Due to the structural and compositional complexity found in interfaces, it is anticipated that they presuppose a concomitant increase in the complexity of the associated regenerative engineering approaches and scaffold designs to achieve successful interface regeneration and seamless integration of the engineered orthopedic tissues. Herein, we discuss the various bioinspired scaffold designs utilized to regenerate orthopedic tissue interfaces. First, we start with discussing the structure-function relationship at the interface. We then discuss the current understanding of the mechanism underlying interface regeneration, followed by discussing the current treatment available in the clinic to treat interface injuries. Lastly, we comprehensively discuss the state-of-the-art scaffold designs utilized to regenerate orthopedic tissue interfaces. Lay Summary Orthopedic tissues are connected to one another through interfaces that play an important role in transitioning mechanical loads between the disparate tissues. After an injury, interfaces must be re-established in order to restore joint function and stability. Understanding the mechanism governing the development of interfaces may lead to successful interface re-establishment and scaffold designs. This article discusses the current knowledge of the structure-function relationship at the interface, the mechanism underlying interface regeneration, and the current treatment available in the clinic to treat interface injuries, as well as bioinspired scaffold designs and engineering strategies to regenerate the complex orthopedic tissue interfaces.