Editorial [Hot Topic: Hyaluronan, A Very Useful Sugar Polymer (Guest Editor: Paul L. DeAngelis) ]

In 1934, the polysaccharide hyaluronan [hyaluronic acid or HA] was extracted from bovine eyes by Karl Meyer. As of early 2008, >22,000 research papers on HA-related science, >1,500 US patents with HA claims, and a ∼$1.5 billion/year market (“Global Markets for Hyaluronic Acid” Millenium Research 2006) definitively prove the value of HA. This sugar polymer is in the same chemical family as heparin, an anticoagulant and an antithrombotic that is the most widely used drug in hospitals. This series of articles describe aspects, both historical and emerging, of HA in the world of pharmacology and biotechnology. The sheer abundance of HA in mammalian tissues in certain structures such as the vitreus of eye, the synovial fluid of joints and the dermis of skin spawned the initial idea that HA was a space filler with superb viscoelastic and hydrating properties. The simple repeating unit structure of HA composed of two monosaccharides, (-beta-4-GlcA-1-beta-3-GlcNAc-1)n, also masked its potential for biological complexity; this prejudice is reminiscent of the ‘boring’ DNA molecule composed of just 4 simple bases! HA is also important for boosting infection by certain microbes; these pathogens coat themselves with a molecule that is identical to vertebrate HA to avoid host defenses. The complex machinery for the synthesis (3 genes) and the degradation (perhaps 7 genes) of HA in mammals as well as its effects on the behavior and the proliferation of a variety of cells suggest that in many circumstances, HA and its metabolic products contain information. In the most current hypotheses, the molecular weight (MW), the amount, and the location of the HA molecule effects its ability to trigger various signals that appear to cue development as well as alter inflammation, cell mobility and adhesion in both health and disease. For example, very large mass (2- 8x106 Da or n=∼103-4) and very small mass (∼103 Da or n=∼2-20) HA molecules can have opposite effects on cells with respect to angiogenesis and to cancer cell growth and metastasis (B. Toole et. al). Thus the recent availability of pure, defined narrow size distribution HA preparations (P. DeAngelis) bode well for drug discovery and development. Purified HA from a variety of sources is used in a variety of medical applications. HA was initially isolated from rooster (chicken) comb and used as medical devices for eye surgeries (E. Balazs) and arthritic pain. Extraction of native and now recombinant bacteria (S. Brown & P. Pummill) is now a significant source of less expensive HA. In addition to the native polymeric form of HA, a variety of chemical analogs have been made to alter its physical properties (G. Prestwich & J. Kuo). Cross-linking or esterification have been used to convert HA from its normal extremely viscous liquid state to more solid forms (e.g., gels, fabrics, etc) with longer biological half-life that retain shape or maintain volume. In the near future, more tissue engineering applications and drug delivery systems (T. Brown) for HA should be in clinical trials. Overall, it is a safe wager that the scope of HA applications will expand with the availability of HA formulations with improved performance and as more HA-related biology becomes elucidated.