Different molecular weights of hyaluronan research in knee osteoarthritis: A state-of-the-art review

•Hyaluronic acid possesses numerous biochemical and biological properties.•We review new molecular insights into the potential of HA to modify OA processes.•Different molecular weights in the formulation of products appear to have varying effects on knee OA (KOA) pain relief, improved function, and postponing.•Intraarticular (IA) HA administration may be an effective option to treat KOA, with a particular emphasis on the use of HA with fewer injections of higher MW, including potential applications of HAs of very HMW. Osteoarthritis (OA), the most common form of arthritis, is characterized by progressive cartilage destruction, concomitant adaptive osteogenesis, and loss of joint function. The progression of OA with aging is associated with a decrease in native hyaluronan (HA, hyaluronate or hyaluronic acid) with a high molecular weight (HMW) in synovial fluid and a subsequent increase in lower MW HA and fragments. As HMW HA possesses numerous biochemical and biological properties, we review new molecular insights into the potential of HA to modify OA processes. Different MWs in the formulation of products appear to have varying effects on knee OA (KOA) pain relief, improved function, and postponing surgery. In addition to the safety profile, more evidence indicates that intraarticular (IA) HA administration may be an effective option to treat KOA, with a particular emphasis on the use of HA with fewer injections of higher MW, including potential applications of HA of very HMW. We also analyzed published systemic reviews and meta-analyses of IA HA in treating KOA in order to discuss their conclusions and consensus statements. According to its MW, HA may offer a simple way to refine therapeutic information in selective KOA.