Aminoacid-enriched sodium hyaluronate enhances keratinocyte scattering, chemotaxis and wound healing through integrin B1-dependent mechanisms

Epithelialisation is a major component of a wound healing and relies on migration and spreading of epidermal keratinocytes. An understading of the mechanisms underlying this process has salient clinical application, as wound healing may pharmacologically modulated to enhance repair of tissue injury. Whilst the efficacy of commercially available hyaluronic acid (HA) formulations in skin tissue repair as well as its action on mesenchymal cells ( e.g. fibroblast and condrocytes) has been well documented, the role of HA in the process of keratinocyte epithelialisation still needs to be addressed in detail. Here, we investigated the efficacy of Aminogam, a compound containing a pool of collagen precursor synthetic aminoacids (1-proline, 1-leucine, 1-lysine and glycine) combined with sodium hyaluronate (SH), in keratinocyte cytokinesis and epithelial wound repair in vitro. Our data show that after wounding, Aminogam-treated cells had higher rates of wound closure than untreated keratinocytes, Cell scattering of three-dimensional multicellular aggregates was 40% increased by Aminogam whereas cell spreading was not affected. Chemokinesis (random migration) and chemotaxis (directional migration) were enhanced by Aminogam at an early and later stage of migration, respectively. Silencing of B1 integrin in HaCat keratinocytes dramatically impaired epithelial cleft repair: wound healing, spreading, scattering and random/directional migration were all decreased 40 to 60 % compared to controls. Aminogam could not improve (p > 0.05) any of these features in the absence of B1 integrin. Our data provide the first evidence that HA , namely Aminogam, exerts direct effects on keratinocyte motility via integrin B1.