%0 Journal Article
%T A biophysically-defined hyaluronic acid-based compound accelerates migration and stimulates the production of keratinocyte-derived neuromodulators
%A Annalisa La Gatta
%A Antonella D¡¯Agostino
%A Chiara Schiraldi
%A Giuseppe Colella
%A Nicola Cirillo
%J Cell Adhesion & Migration
%D 2019
%R https://doi.org/10.1080/19336918.2018.1494997
%X ABSTRACT Hyaluronic acid (HA) preparations are widely used in clinical practice and recent data suggest that commercially available HA-based compounds promote ulcer re-epithelialization and induce pain relief. However, the pathophysiological basis of these effects remains poorly understood. In the present study, we investigated the biophysical, biomolecular and functional properties of a HA preparation combined with a pool of collagen precursor synthetic aminoacids, namely l-proline, l-leucine, l-lysine and glycine (Aminogam£¿). Hydrodynamic characterization of Aminogam£¿ by size exclusion chromatography-triple detector array (SEC-TDA) revealed an average molecular weight in the range of 700¨C1700 kDa. Rheological measurements of the 1700kDa Mw lot showed a pseoudoplastic behaviour with a zero-shear viscosity (¦Ç0) equal to 90 ¡À 9 Pa£¿s at 25¡ãC and 55 ¡À 6 Pa£¿s at 37¡ãC. Automated time-lapse videomicroscopy studies in a fibroblast-free system demonstrated that 1% (v/v) Aminogam£¿ significantly reduced the healing time of wounded keratinocyte monolayers. In AKGOS assays, Aminogam£¿ stimulated cellular locomotion (chemokinesis) and directional migration (chemotaxis) of keratinocytes. Analysis of microarray data suggested that keratinocytes had a functional neuroendocrine machinery, and this was confirmed by testing the secretion of six neuroactive molecules by ELISA, namely ¦Á-MSH, ¦Â-endorphins, melatonin, substance P, cortisol, and neurotensin. Interestingly, Aminogam£¿ regulated the production of several neuropeptides, including ¦Â-endorphins. In conclusion, our data shed light on the epithelial-dependent mechanisms that underlie the efficacy of Aminogam£¿, particularly in reference to wound healing and nociception
%U https://www.tandfonline.com/doi/full/10.1080/19336918.2018.1494997