Glycosaminoglycans in Wound Healing

Glycosaminoglycans (GAGs) are ancient molecules that have persisted throughout vertebrate and invertebrate evolution for many hundreds of millions of years. They have essential roles in the regulation of many fundamental physiological processes, which control cellular proliferation, differentiation, matrix assembly, homeostasis, and cellular behavior, which has ensured the survival of vertebrates and invertebrates to the present day. In this study, we review the roles of GAGs in wound repair in a number of tissues. The healing of some wounds such as diabetic ulcers, cartilaginous defects, and damaged neural tissue can be a particularly demanding clinical problem. However, with the directive roles that GAGs have established through evolution, the development of key matrix and cellular molecules to control cellular behavior has resulted in the development of sophisticated control systems to regulate key physiological life-preserving processes. The control of wound repair is but one example of these. With a greater understanding of how GAGs actually do this, inroads are being made in the application of this information in the development of therapeutic procedures to improve repair of these problematic tissues. The application of engineered heparin sulfate (HS), human natural killer-1 (HNK-1), and HS biomimetics in neuromuscular repair biology, activated protein C in the treatment of diabetic ulcers, and affinity-isolated HS subfractions for specific applications in bone and vascular repair and in the improved expansion of mesenchymal stem cells for therapeutic applications represent significant advances in wound repair biology and emphasize the importance of GAGs in these processes. Armed with a greater understanding of the glycocode and the roles of GAGs in such repair processes, further improvements in therapeutic interventions are likely in the area of repair biology.