Hyaluronic acid (HA), a natural linear macromolecular polysaccharide, is composed of repeated disaccharide units (D-glucuronic acid and N-acetylglucosamine). It is widely present in human tissues, especially in the dermis of the skin, synovial fluid and vitreous body of the eye. Its unique molecular structure gives it excellent hydrophilicity, and each gram of HA can bind up to 1000 times its own weight of water molecules. This property makes it have core value in the fields of medicine (such as viscoelastic agents for ophthalmic surgery, osteoarthritis injections), skin care (high-efficiency moisturizers) and tissue engineering.
Historically, commercial acquisition of hyaluronic acid has mainly relied on animal tissue extraction, especially rooster combs. However, this method has obvious limitations: limited raw material sources, low yields, complicated separation and purification steps, and animal-derived protein impurities may remain in the final product, bringing potential immunogenicity risks. These factors have jointly restricted the widespread application and cost control of hyaluronic acid.
The core technology of modern industrial large-scale production of hyaluronic acid is microbial fermentation. This process relies on specially selected, non-pathogenic microbial strains - mainly specific subspecies of Streptococcus equi subsp. zooepidemicus, or some safely modified Bacillus subtilis. In a strictly controlled bioreactor environment, these microorganisms use sterilized culture media containing carbon sources (such as glucose), nitrogen sources (such as yeast extract) and inorganic salts for aerobic growth.
The key is that these high-yield strains have been genetically engineered or carefully screened, and their cellular metabolic pathways have been optimized, which can efficiently convert the ingested carbon source substances into hyaluronic acid molecules and secrete them into the fermentation broth. The entire microbial fermentation process requires precise control of parameters such as temperature, pH value, dissolved oxygen concentration and stirring rate for several hours to several days to maximize the production of hyaluronic acid. After the fermentation is completed, the mixed solution undergoes multiple physical (such as centrifugation, filtration) and chemical (such as precipitation, chromatography) purification steps to remove bacteria, residual culture medium components and other impurities, and finally obtain high-purity hyaluronic acid powder or solution.
Compared with traditional animal extraction methods, the microbial fermentation route has significant advantages: stable raw material supply and low cost (based on renewable sugars); highly controllable production process, which can achieve automated large-scale production; high product purity and excellent batch-to-batch consistency, avoiding the risk of animal-borne disease transmission or immunogenicity; at the same time, by adjusting the fermentation strain and process parameters, the molecular weight range of the final product can be precisely controlled to meet the specific requirements of hyaluronic acid performance in different application scenarios (such as small molecule transdermal absorption and large molecule long-term lubrication).
Therefore, microbial fermentation technology has completely dominated the global hyaluronic acid production pattern. It is not only a more effective alternative to traditional methods, but also a key cornerstone for driving the continuous innovation and popularization of hyaluronic acid in the fields of medical health, personal care and even food. The precise and powerful production capacity of modern fermentation engineering ensures that this precious biological molecule can serve the vast market efficiently and safely.
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