Hyaluronic Acid

Hyaluronic acid is a linear polymer of alternating D-glucuronic acid and N-acetylglucosamine, made at the plasma membrane by hyaluronan synthases, which extrude the growing chain directly into the extracellular space. It carries no sulfate and no core protein, unlike every other glycosaminoglycan. Native chains reach into the millions of daltons and signal through receptors including CD44, so it is a structural water-holder and a signalling molecule at once.

Roughly half of the body's hyaluronan is in skin, and it is remarkably short-lived there, with tissue turnover measured in about a day, by hyaluronidases and free radicals, with clearance through lymph to the liver. Injectable fillers crosslink it, commonly with butanediol diglycidyl ether, to slow that degradation; crosslinked hyaluronic acid fillers have been FDA-approved since the early 2000s and are unusual in being reversible by injected hyaluronidase. Topically, high molecular weight hyaluronan stays on the surface as a humectant film, since nothing of that size crosses intact stratum corneum.

Route is the whole story. An injected crosslinked gel provides volume for months; a topical solution provides surface hydration a corneometer will detect, ending when the film is removed. Neither is the same as increasing endogenous hyaluronan, which is a synthesis question rather than a delivery one.

The frequently quoted figure that hyaluronic acid binds a thousand times its weight in water describes the polymer in solution, not a serum on a face, and in a dry environment a humectant film can draw water outward and leave skin feeling worse. Low molecular weight hyaluronan is marketed as the penetrating version, but fragment size is itself a biological signal: long chains are broadly anti-inflammatory, while short fragments are recognised as damage signals and are pro-inflammatory.