Proteoglycans and proteoglycan mimetics for tissue engineering

Proteoglycans play a crucial role in proper tissue morphology and function throughout the body that is defined by a combination of their core protein and the attached glycosaminoglycan chains. Although they serve a myriad of roles, the functions of extracellular proteoglycans can be generally sorted into four categories: modulation of tissue mechanical properties, regulation and protection of the extracellular matrix, sequestering of proteins, and regulation of cell signaling. The loss of proteoglycans can result in significant tissue dysfunction, ranging from poor mechanical properties to uncontrolled inflammation. Because of the key roles they play in proper tissue function and due to their complex synthesis, the past two decades have seen significant research into the development of proteoglycan mimetic molecules to recapitulate the function of proteoglycans for therapeutic and tissue engineering applications. These strategies have ranged from semisynthetic graft copolymers to recombinant proteoglycan domains synthesized by genetically engineered cells. In this review, we highlight some of the important functions of extracellular proteoglycans, as well as the strategies developed to recapitulate these functions.