The word hyaluronic is derived from the Greek hyalos meaning “glass” or “transparent” and refers to the vitreous humor, the ocular tissue from which it was first isolated by Karl Meyer and colleagues in 1934. It was later located in many other animal tissues, i.e. synovial fluid, cartilage and the umbilical cord, where it has the same structure and biological activities, described in this article. Hyaluronic acid (HA)is a linear polysaccharide of high molecular weight that belongs to the family of mucopolysaccharides or glycosaminoglycans (GAGs), the physiological constituents of the dermal connective tissue in the extracellular matrix. In adult humans, the total amount of HA is equal to approximately 15 g, half of which is found in the skin.
At the skin compatible pH of 7, the carboxylic groups of HA are almost totally ionized, thus forming a polyanionic structure that imparts excellent hydro-coordinating properties in skin. This structure is mainly produced by skin keratinocytes and fibroblasts whose complete renewal cycle takes 2–4.5 days1—a much shorter time than the collagen cycle, which takes 60–70 days.2
Due to the functions HA serves in skin homeostasis, both its synthesis and degradation must be rapid and wellcontrolled by biological mechanisms. Indeed, it is an active physiological polymer that not only fulfills structure and filling functions, but also supplies water in the skin. In fact, due to its chemical structure, it is able to retain large amounts of water; for example, one gram of HA may act as a ligand for up to 6 L of water.3 Further, HA forms a scleroproteic sheath on fibrous protein, thus ensuring appropriate lubrication.
Similar to a biological sponge, HA resists compression and imparts structure to the dermis. This is due to its electrostatic interactions with collagen fibers, matrix proteins and other GAGs that form large-sized, “bottlebrushshaped” aggregates called proteoglycans. The structural organization of the extracellular matrix stabilizes the orientation of collagen fibers, preventing them from becoming too close and forming links among fibrils, in turn developing into insoluble collagen and toughening the skin, as occurs with age.
Finally, HA, fully surrounded by its hydration sphere, facilitates the extracellular transport of ions, solutes and metabolites, much like a chromatographic column. In addition, it affects the migration, differentiation, growth and adhesion of cells; angiogenesis; and control of the immune response.1, 3–6