Important events in research on hyaluronan products.
Time
Event
1880
Portes reported that mucin from the vitreous body differs from other mucoids in cornea and cartilage and named it hyalomucine [2].
1934
Meyer and Palmer isolated and identified the polysaccharide from the vitreous body and named it hyaluronic acid [3].
30s–50s
Hyaluronan from many different tissues of vertebrates was isolated, identified, and characterized. A few pathogenic bacteria were found that produce hyaluronan and use it to encapsulate their cells.
50s
The chemical structure of hyaluronan was elucidated by Karl Meyer and his team. They used hyaluronidase to produce overlapping oligosaccharides that were structurally analyzed by conventional techniques [4]. Interest emerged to use hyaluronan in eye surgery as a substitute of the vitreous body.
40s–70s
Extraction processes from animal tissues were optimized to remove protein and to minimize hyaluronan degradation. First studies on hyaluronan production through bacterial fermentation and chemical synthesis were initiated.
1979
First patent on ultrapure hyaluronan isolated from rooster combs [5]. This was the starting of the industrial manufacturing of hyaluronan from animal sources for human applications. In 1980, using the methods of Balasz Pharmacia (Sweden) introduced Healon, a product used in cataract surgery.
90s–00s
Revival of studies on bacterial fermentation to produce hyaluronan of high molecular weight. Emphasis on controlling polymer size and polydispersity.
1993
The gene encoding for a single enzyme that polymerizes UDP-GlcNAc and UDP-GlcUA into hyaluronan is isolated by DeAngelis and coworkers from Streptococcus pyogenes. Hyaluronan synthases from other microorganisms were identified and characterized [6, 7].
1996
The largest hyaluronan fragment, an octamer, was chemically synthesized through controlled addition of disaccharide units [8].
2003
Research on the enzymatic synthesis of hyaluronan and monodisperse hyaluronan oligosaccharides with defined length [9, 10].
