Biomimetic Proteoglycans and the Biological Interface: Applications in Molecular Engineering and Regenerative Medicine

Abstract Proteoglycans are ubiquitous and physiologically active components of the extracellular matrix. The atomic, molecular, and macromolecular chemical structure and organization of proteoglycans contribute to the biological activity and biophysical functioning within the extracellular matrix. Disruption in proteoglycan biosynthesis, caused by genetic mutations or cell phenotype, can lead to disease and aberrant pathology. Structural alterations to proteoglycans have also been implicated in disease and pathology. The structure, processing, and function of proteoglycans are intertwined. Deviations from homeostasis can profoundly affect biological functioning. To address these issues and better understand proteoglycan behavior, scientists have sought to recapitulate proteoglycan components and the molecular and macromolecular structure/property relationships in proteoglycans. To accomplish this, researchers have designed biological mimics for native proteoglycans, termed proteoglycan mimics and biomimetic proteoglycans. In this review, we examine the materials design behind proteoglycan mimics, showcasing their applications in different tissue types for molecular engineering. Additionally, we showcase the use of proteoglycan mimics to study the interaction between the designed material and the biology it interacts with, termed the biological interface. Lastly, we discuss how understanding the biological interface has led to research on the implementation of biomimetic proteoglycans for tissue regeneration with the potential to be used as a regenerative medicine. This review aims to honor Nicholas A. Peppas for his landmark contributions to the field of regenerative engineering and functional biomaterials. Lay Summary Proteoglycans are macromolecules containing a protein core with one or more sugar side chains, called glycosaminoglycans. Proteoglycans are important for the structure and maintenance of healthy tissue. As proteoglycans degrade, tissue becomes unhealthy, causing disorder and disease. To fix this, researchers have designed biological mimics for proteoglycans. Since proteoglycans are common throughout the body, the applications of proteoglycan mimics for molecular engineering are endless. This work discusses the importance of designing biological mimics to native proteoglycans found within the human body.