margin, in the connective tissue matrix, and collocating with CD44 expression in migrating keratinocytes. Medical uses Hyaluronic acid has been FDA-approved to treat osteoarthritis of the knee via intra-articular injection. A 2012 review showed that the quality of studies supporting this use was mostly poor, with a general absence of significant benefits, and that intra-articular injection of HA could possibly cause adverse effects. A 2020 meta-analysis found that intra-articular injection of high molecular weight HA improved both pain and function in people with knee osteoarthritis. Hyaluronic acid has been used in various formulations to create artificial tears to treat dry eye. Hyaluronic acid is a common ingredient in skin care products. Hyaluronic acid is used as a dermal filler in cosmetic surgery. It is typically injected using either a classic sharp hypodermic needle or a micro-cannula. Some studies have suggested that the use of micro-cannulas can significantly reduce vessel embolisms during injections. Currently, hyaluronic acid is used frequently as a soft tissue filler due to its bio-compatibility and possible reversibility using Hyaluronidase Complications include the severing of nerves and microvessels, pain, and bruising. Some side effects can also appear by way of erythema, itching, and vascular occlusion; vascular occlusion is the most worrisome side effect due to the possibility of skin necrosis, or even blindness in a patient. In some cases, hyaluronic acid fillers can result in a granulomatous foreign body reaction. Sources Hyaluronic acid is produced on a large scale by extraction from animal tissues, such as chicken comb, and from Streptococci. Structure Hyaluronic acid is a polymer of disaccharides, which are composed of D-glucuronic acid and N-acetyl-D-glucosamine, linked via alternating β-(1→4) and β-(1→3) glycosidic bonds. Hyaluronic acid can be 25,000 disaccharide repeats in length. Polymers of hyaluronic acid can range in size from 5,000 to 20,000,000 Da in vivo. The average molecular weight in human synovial fluid is 3–4 million Da, and hyaluronic acid purified from human umbilical cord is 3,140,000 Da; other sources mention average molecular weight of 7 million Da for synovial fluid. Hyaluronic acid also contains silicon, ranging 350–1,900μg/g depending on location in the organism. Hyaluronic acid is energetically stable, in part because of the stereochemistry of its component disaccharides. Bulky groups on each sugar molecule are in sterically favored positions, whereas the smaller hydrogens assume the less-favorable axial positions. Hyaluronic acid in aqueous solutions self-associates to form transient clusters in solution. While it is