Introduction

Hyaluronan is a non-sulfated glycosaminoglycan (GAG), consisting of repeating units of (b,1-4)-D-glucuronic acid-(b,1-3)-N-acetyl-D-glucosamine. HA occurs normally as a part of the ECM of almost all tissues in a high molecular weight (HMW) polymer (> 106 kDa), and the highest concentrations are found in brain, skin and the central nervous system. Originally, it was believed that the physiological function of HA was only structural (1). However, HA is now recognized as a pharmacological...

References

Truppe W, Basner R, von Figura K, Kresse H. Uptake of hyaluronate by cultured cells. Biochem Biophys Res Commun 1977 78 713-719. 2. Underhill CB, Dorfman A. The role of hyaluronic acid in intercellular adhesion of cultured mouse cells. Exp Cell Res 1978 117 155-164. 3. Underhill CB, Toole BP. Binding of hyaluronate to the surface of cultured cells. J Cell Biol 1979 82 475-484. 4. Love SW, Shannon BT, Myrvik QN, Lynn WS. Characterization of macrophage agglutinating factor as a hyaluronic acid...

Hyaluronan Structures in Solution Relevance to Tissue Biologic Functions and Aging

Extracellular HA is a polydisperse molecule whose molecular weight ranges from 300 to > 103 kDa (37,38). It displays both flexible and stiff domains in solution, suggesting deviation of its primary structure from that elucidated by Meyer and co-workers, which is an unbranched chain of alternating D-GlcA and D-GlcNAc in a 1 1 molar ratio (1,2,39). The secondary and tertiary structures of HA may be determined by its primary structure (sugar-sequence) like in proteins (40). If this is the case,...

Viscosupplementation A Hyaluronan in the Joint

Image Elastic Modulus

The rheological properties of synovial fluid and purified hyaluronan were first systematically studied by the author and his co-workers in the 1960s using both healthy and arthritic human and equine synovial fluids and purified hyaluronan 94-96 . Fig. 5 demonstrates the rheological properties of two pooled human synovial fluid samples obtained from healthy knee joints and one from osteoarthritic joints 95 . The synovial fluids of healthy young 27-34 years and old 52-78 years subjects, when...

Acknowledgements

This work has been partly supported through an R01 grant number AR47433 to APS and a Scientist Development Award 0030184N from the American Heart Association National office to APS. This chapter is based on an invited review article published by us in the Glycoconjugate Journal with permission 50 . Fig. 2 was printed with permission from the Journal of Clinical Investigation 6 . 1. Watanabe H, Kimata K, Line S, Strong D, Gao LY, Kozak CA, Yamada Y. Mouse cartilage matrix deficiency cmd caused...

Conclusions

Hyaluronan possesses a combination of unique physical properties and biological functions that allow it to serve as an important starting material for the preparation of new biocompatible and biodegradable polymers. This review highlights the chemistries involved in the modification of hyaluronan, and the potential medical applications of these hyaluronan-based biomaterials. Important new products have already reached the marketplace, and the approval and introduction of an increasing number of...

Degradation by Nonenzymatic Means

In contrast to being a chemical compound stable under normal physiological conditions, chain scission of the HA polymer can be induced in an unspecific manner by chemical reactions other than enzyme-catalyzed degradation as well as by physical stresses such as freeze-drying, shearing or stirring at critical conditions. Moreover, irradiation can cause depolymerization. In line with this, it was found that free radicals can interact with HA and cause degradation of the polymer 53 . Cells form...

RHAMM Expression Influences Wound Repair and Tumor Progression

Cd168 Cell Surface

Alternative Use of CD44 and RHAMM in Tissue Response to Injury Processes The importance of expression profiles of HABPs for cell response to HA was recently demonstrated by a study performed by Nedvetzky et al. 126 . In this study, the role of CD44 in collagen II-induced arthritis was analyzed. Surprisingly, whereas CD44 mice developed arthritis 25 days after a single injection of collagen II, a second injection was necessary to induce arthritis in wild-type wt mice. This difference was...

Hyaluronan in Matrix and Tissue Engineering

Tissue engineering with hyaluronan addresses the fundamental issue of how the various intercellular macromolecules, primarily collagens, proteoglycans and hyaluronan affect the assembly of cells by providing intercellular scaffolding. The question is how hyaluronan or its derivatives can allow, or in combination with other structural matrix molecules, can help organize cells in vitro to form tissues or help to integrate such cell assemblies into living organs. The role of hyaluronan can be...

Hyaluronan Preparations Used for Viscosupplementation in the Joints

Side Effects Supartz Injections

The first hyaluronan preparation used for intra-articular injection was the so-called non-inflammatory fraction of the natrium salt of hyaluronan NIF-NaHA and it had an average molecular weight of 2-3 million. This name was given to this highly purified preparation because it was distinctly different from the other fraction of the molecule that caused inflammatory reactions in various tissues used for testing such as the vitreus of the owl monkey, the peritoneal cavity of mouse and the horse...

Tammi Cahill Tc Repair And Custom Designs Linkedin

Roden L, Campbell P, Fraser JR, Laurent TC, Pertoft H, Thompson JN. Enzymic pathways of hyaluronan catabolism. Ciba Found Symp 1989 143 60-76. 2. Fraser JR, Brown TJ, Laurent TC. Catabolism of Hyaluronan. The Chemistry, Biology and Medical Applications of Hyaluronan and Its Derivatives. London Portland Press, 1998 92-95. 3. Laurent TC, Fraser JR. Hyaluronan. Faseb J 1992 6 2397 -2404. 4. Knudson W, Chow G, Knudson CB. CD44-mediated uptake and degradation of hyaluronan. Matrix Biol 2002 21...

Preparation and Isolation of Hyaluronan Oligomers A Degradation of Hyaluronan

Hyaluronan can be degraded to smaller fragments by chemical methods acidic and alkaline conditions , physical stress high-speed stirring or critical shearing , sonication 38 , free-radical-based cleavage 39 , or enzymatic methods. Free-radical-based cleavage of hyaluronan in the connective tissue has physiological implications in arthritis and aging. The hydroxyl radical has been shown to be a primary factor in the initiation of hyaluronan degradation by causing non-specific scission of the...

Therapeutic Applications

Elastoviscous hyaluronan solutions crowded molecular networks and elasto-viscous hyaluronan gels cross-linked molecular networks have been used in several therapeutic areas. In order to emphasize that in all these therapeutic uses the primary mode of action is based on the viscous and elastic properties of a crowded molecular network, we designated the diverse uses as follows viscosurgery, used in ophthalmic surgery to protect delicate eye tissues and provide space during surgical manipulation...

D SHAPHyaluronan Complex and Inflammatory Bowel Disease

Crohn's disease and ulcerative colitis are the major chronic inflammatory diseases of the gastrointestinal tract. They are often referred to together as inflammatory bowel disease IBD . The main pathological changes include an increase in intestinal mucosal mononuclear leukocytes and a dramatic hyperplasia of muscularis mucosae 75 . The interaction between recruited leukocytes and mesenchymal smooth muscle cells is thought to be important in Figure 4 The collagen-induced arthritis is...

Summary and Conclusion A Summary

HA is an acidic GAG of D-GlcA and D-GlcNA that is found in mammalian connected tissue. It is a polydisperse, unbranched chain whose molecular weight varies from 300 to gt 103 kDa. HA occurs as a free chain and covalently bonded to protein as the SHAP-HA complex. It can be found inside and outside the cells. Its secondary and tertiary structures in solution display both stiff and flexible domains that suggest deviations of its primary structure sugar-sequence from the alternating sequence of the...