Glycosaminoglycans in Wound Healing

Abstract

ABSTR ACT: 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.

The multifaceted roles of perlecan in fibrosis

“…It is now well accepted that fibrosis is not a static event, but a dynamic process involving several phases that are also common to the wound healing response. Initially, an influx of inflammatory cells are seen that become activated resulting in the downstream activation of tissue resident ECM secreting cells followed by a significant change in the structure of ECM from an increased synthesis and decreased proteolytic turnover, further immune cell infiltration and delayed apoptosis [4,5]. Many of these phases involve heparin-binding growth factors, cytokines and chemokines suggesting that heparan sulfate (HS) proteoglycans play important roles in this process [6].…”

The Strategies of Natural Polysaccharide in Wound Healing

“…GAG is the important constituent of the extracellular matrix found on cell surfaces [14] and widely distributed in connective tissues. GAG is composed of characteristic repeating disaccharides, with specific monosaccharides sulfated at each of C 2 , C 3 , C 4 , and C 6 [15]. These compounds are highly anionic polymers, which interact with many cationic species (such as ions and proteins) due to the presence of the carboxylic acid and sulfate functional groups [16].…”

“…The ECM contains a network of scaffold proteins that are linked by GAG. GAG, especially HS, plays a key role as anticoagulants that have important acts to manage the regulations of many of the serpins [15]. HS represents 50-90% of the total GAG content [25] and is only in contact with blood when an injury occurs [26,27].…”

“…Both of them act to form an unstructured connective tissue medium that provides new cells to migrate. A number of PGs were presented in the wound site, and their GAG side chains were involved in the stabilization and activation of growth factors [15]. Sulfated PGs with CS and DS contribute in collagen polymerization [39], and HS PGs on cells can create anchors to the surrounding matrix [40].…”

A Perspective on the Potential Utility of a Viscosupplement Multifunctional Biotherapeutic

“…The sophistication of the ECM is in part due to its component glycosaminoglycans (GAGs) which are ancient molecules that evolved over a 500 million year period of vertebrate and invertebrate evolution to become cellular mediators in the glycocalyx . GAGs are molecular recognition and information conveyancing motifs that actuate cellular responses through variable sulphation patterns which determine their interactive properties with growth factors, chemokine's, cytokines, enzymes, inhibitory proteins, morphogenetic proteins, and with structural matrix components which enhances their properties and aids in the stabilization, development, and functional properties of tissues . The GAGs of the glycocalyx constitute an interactive frontier and the first point of contact between a cell and its neighbor that cell and ECM component or that cell and any invading organism, GAGs facilitate cell–cell and cell–ECM communication .…”