The bioengineering application of hyaluronic acid in tissue regeneration and repair

The multifaceted role of hyaluronic acid (HA) across diverse biomedical disciplines underscores its versatility in tissue regeneration and repair. HA hydrogels employ different crosslinking including chemical (chitosan, collagen), photo- initiation (riboflavin, LAP), enzymatic (HRP/H2O2), and physical interactions (hydrogen bonds, metal coordination). In biophysics and biochemistry, HA's signaling pathways, primarily through CD44 and RHAMM receptors, modulate cell behavior (cell migration; internalization of HA), inflammation, and wound healing. Particularly, smaller HA fragments stimulate inflammatory responses through toll-like receptors, impacting macrophages and cytokine expression. HA's implications in oncology highlight its involvement in tumor progression, metastasis, and treatment. Elevated HA in tumor stroma impacts apoptosis resistance and promotes tumor growth, presenting potential therapeutic targets to halt tumor progression. In orthopedics, HA's presence in synovial fluid aids in osteoarthritis management, as its supplementation alleviates pain, enhances synovial fluid's viscoelastic properties, and promotes cartilage integrity. In ophthalmology, HA's application in dry eye syndrome addresses symptoms by moisturizing the eyes, replenishing tear film deficiencies, and facilitating wound healing. Intravitreal injections and hydrogel-based systems offer versatile approaches for drug delivery and vitreous humor replacement. For skin regeneration and wound healing, HA hydrogel dressings exhibit exceptional properties by promoting moist wound healing and facilitating tissue repair. Integration of advanced regenerative tools like stem cells and solubilized amnion membranes into HA-based systems accelerates wound closure and tissue recovery. Overall, HA's unique properties and interactions render it a promising candidate across diverse biomedical domains, showcasing immense potentials in tissue regeneration and therapeutic interventions. Nevertheless, many detailed cellular and molecular mechanisms of HA and its applications remain unexplored and warrant further investigation. •HA hydrogels employ different crosslinking, including chemical (chitosan, collagen), photo- initiation (riboflavin, LAP), enzyme (HRP/H2O2), and physical interactions (hydrogen bonds, metal coordination).•HA's signaling pathways, primarily through CD44, RHAMM receptors, modulate cell behavior, inflammation, and wound healing.•In orthopedics, HA's presence in synovial fluid aid