Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory

Abstract

Hyaluronic acid (also known as hyaluronan or hyaluronate) is naturally found in many tissues and fluids, but more abundantly in articular cartilage and synovial fluid (SF). Hyaluronic acid (HA) content varies widely in different joints and species. HA is a non-sulfated, naturally occurring non-protein glycosaminoglycan (GAG), with distinct physico-chemical properties, produced by synoviocytes, fibroblasts, and chondrocytes. HA has an important role in the biomechanics of normal SF, where it is partially responsible for lubrication and viscoelasticity of the SF. The concentration of HA and its molecular weight (MW) decline as osteoarthritis (OA) progresses with aging. For that reason, HA has been used for more than four decades in the treatment of OA in dogs, horses and humans. HA produces anti-arthritic effects via multiple mechanisms involving receptors, enzymes and other metabolic pathways. HA is also used in the treatment of ophthalmic, dermal, burns, wound repair, and other health conditions. The MW of HA appears to play a critical role in the formulation of the products used in the treatment of diseases. This review provides a mechanism-based rationale for the use of HA in some disease conditions with special reference to OA.

Marine-Derived Polymeric Materials and Biomimetics: An Overview

“…The chemical or enzymatic addition of functional groups is a way to enhance HA mechanical strength and control its biodegradation making it tunable for use as scaffold in regenerative medicine [20,26]. A large variety of HA/HA-derivatives formulations are accessible and their curative effects mostly depend on their rheological properties and administration routes [19]. The most common sources of HA are connective tissues containing synovial fluid, eyeball vitreous fluid, umbilical cords and rooster combs [11][12][13].…”

“…These aspects influence their ability to interact with proteins and are the principal factor determining therapeutic properties [18]. For HA, size has been shown to be the principal factor that governs its physico-chemical properties [19]. The tight control of HA structure and concentration plays a role in cell proliferation and migration but also in angiogenesis and inflammation [20].…”

“…HA is actively used for drug and growth factor delivery, or as scaffolding material to stimulate bone healing and biomineralization [22]. Notably, osteoarthritis has been treated with HA for more than 40 years [19].…”

Polysaccharide-Based Formulations for Healing of Skin-Related Wound Infections: Lessons from Animal Models and Clinical Trials

“…Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan composed by repeated disaccharides of β-1,4-linked D-glucuronic acid and β-1,3-linked N-acetyl-d-glucosamine [97]. It is found as the main component of extracellular matrix in hydrated tissues, including skin where it plays essential roles in cellular migration and inflammation during tissue regeneration [97][98][99][100]. This naturally occurring polymer has some characteristics (wide availability, biocompatibility, and safety) that make it a suitable material for wound dressings [101][102][103].…”

Use of Hyaluronic Acid Injection after Arthroscopic Release in Lateral Patellar Compression Syndrome with Degenerative Cartilage Changes: Randomized Control Trial

“…[4][5][6][7][8] Hyaluronic acid is a natural component of the synovial uid and responsible for its elastic features and function of articular surfaces [9,10]. Intra-articular injection of Hyaluronic acid is one of the recommendations for treatment of degenerative joint diseases [11][12][13][14][15][16][17].…”