Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application

Tissue regeneration is orchestrated by both intracellular signaling programs and extracellular matrix remodeling. Glycosaminoglycans (GAGs) are essential sugar chains ubiquitously expressed throughout the body. Their spatiotemporal turnover is an important part of normal organ biology and essential to tissue repair following injury. Glycoscience is a hot topic and is its role in organ physiology is being increasingly unraveled due to both scientific and technological advances. The mechanistic understanding of GAG regulation and manipulation is multidisciplinary effort, spanning biology, chemistry, materials science and translational medicine. This review broadly examines how GAG biology is naturally regulated and precisely controlled in health and disease, including data analysis from a stem cell-based model of liver disease. Despite being limited in types, GAGs successfully regulate complex cell and tissue level biology. We also discuss preclinical and clinical applications of GAGs, with a focus on biomaterials for tissue engineering and precision drug delivery, stressing their importance in biomedical engineering and clinical therapy. In addition, we outline state-of-art detection techniques and molecular modeling tools for analyzing GAG quantity, structure and interactions with other molecules. This review provides a timely and comprehensive overview of GAG biology highlighting their role in tissue repair and engineering, and outlines future directions for their design and next-generation therapies.