Introduction
Orthopedic injuries and diseases commonly affect soft tissues, including cartilage, which line the surface of articulating joints, as well as ligaments and tendons, which connect bone to bone and muscle to bone, respectively. Continued developments in tissue engineering have led to advancements in the regeneration of these tissues, while recently emphasis has been placed on the regeneration of the interfaces or insertion sites that connect these soft tissues to bone, which are characterized by a gradient of structural and mechanical properties [1]. The integrity of these regions is essential to facilitating synchronized joint motion, mediating load transfer between distinct tissue types, and sustaining heterotypic cellular communications necessary for interface function and homeostasis [2–4]. These critical junctions are also prone to injury, and healing is typically incomplete after surgical repair. The need for functional interface regeneration is highlighted by the fact that failure to restore the intricate tissue-to-tissue interface has been reported to compromise graft stability and long-term clinical outcome [5, 6].
Fundamentally, tissue engineering involves the use of cells, growth factors, and/or biomaterial scaffolds in a variety of ways to engineer tissues in vitro and in vivo. The principles of tissue engineering have been applied for the successful formation of connective tissues, including bone, cartilage, ligament, and tendon. Recently the focus in the field has shifted from tissue formation to tissue function [7], specifically to imparting physiologically relevant functionality to tissue-engineered grafts. One of the most significant challenges to clinical application is achieving biological fixation of musculoskeletal grafts with each other as well as to the native host environment [8].