Hyaluronic acid (HA) is a carbohydrate, more specifically a mucopolysaccharide, occurring naturally in all living organisms. It can be several thousands of sugars (carbohydrates) long. When not bound to other molecules, it binds to water giving it a stiff viscous quality similar to "Jell-o" [
16]. Hyaluronic acid was discovered in bovine vitreous humor by Meyer and Palmer in 1934 [
17]. It is most frequently referred to as HA due to the fact that it exists
in vivo as a polyanion and in the protonated acid form [
18]. The term "hyaluronan" was introduced in 1986 by Endre Balazs to conform with the international nomenclature of polysaccharides [
19]. HA is an agent which is known to reduce the extent of scar formation by inhibiting lymphocyte migration, proliferation and chemotaxis granulocyte fagocitosis and degranulation, and macrophage motility [
20]. The predominant mechanism of HA is unknown;
in vivo,
in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. Of these effects, worth mentioning is its chondroprotective effects
in vitro and
in vivo (orthopedic application). HA has also been successfully used in ophthalmology, cardiovascular system, dermatology, and wound healing [
16]. HA is a major component of the extracellular matrix, and it plays an important role in the early wound healing process [
21]. HA is an endogenous stimulator of interleukin-1 (IL-1) production and IL-1 affects fibroblasts proliferation and collagenase production [
22]. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the reproduction and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. These functions are manifested in the scavenging of reactive oxygen-derived free radicals, the inhibition of immune complex adherence to polymorphonuclear cells, the inhibition of leukocyte and macrophage migration and aggregation, and the regulation of fibroblast proliferation [
23]. HA and its derivatives may also promote regeneration of injured nerves through realignment of the fibrin matrix, and they can provide a suitable environment for axonal ingrowth. Use of the hyaluronic acid-carboxymethylcellulose (HA CMC) membrane Seprafilm as a solid anti-adhesion barrier agent is one of the therapeutic approaches to deduce postoperative scar formation and is effective in promoting peripheral nerve regeneration at the repair site [
24],[
25]. HA gel significantly reduces nerve adhesions after type nerve injured [
26]. Mohammad et al. describe the early effect on nerve regeneration of continuous local delivery of nerve growth factor (NGF) and the local incorporation of HA inside a newly manufactured nerve conduit material from fresh human amniotic membrane. Human amniotic membrane contains important biochemical factors that play a major neurotrophic role in the nerve regeneration process [
27].