A biophysically-defined hyaluronic acid-based compound accelerates migration and stimulates the production of keratinocyte-derived neuromodulators

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 700-1700 kDa. Rheological measurements of the 1700kDa M lot showed a pseoudoplastic behaviour with a zero-shear viscosity (η) equal to 90 ± 9 Pa∙s at 25°C and 55 ± 6 Pa∙s at 37°C. 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 α-MSH, β-endorphins, melatonin, substance P, cortisol, and neurotensin. Interestingly, Aminogam® regulated the production of several neuropeptides, including β-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.

Amino Acid-Enriched Formula for the Post-Operative Care of Extraction Sockets Evaluated by 3-D Intraoral Scanning

“…This gel, thanks to its local administration and substantivity, promotes the deposition of components of the extracellular matrix and the production of cytokines, thus accelerating the wound healing process. Moreover, hyaluronic acid binds many water molecules, and so also improves tissue hydration and cellular resistance to mechanical damage [ 19 , 20 ].…”

High molecular weight hyaluronic acid drastically reduces chemotherapy-induced mucositis and apoptotic cell death

“…Concentrations of HA constituents used; Mucosamin ® , H-MW-HA (1% and 5%, v/v), xl-HA 5/5, xl-HA 30/30, and xl-HA 100/100 (0.01% v/v) and xl-HA (100/100). Concentrations of all HA constituents were chosen for potential safe efficacy, as determined by preliminary experiments (data not shown) and potential therapeutic efficacy of HA-based compound (Mucosamin ® ) [ 28 , 76 ]. To determine the potential protective effect of HA constituents on H 2 O 2 -induced damage in oral keratinocyte cells, cell viability was assessed using fluorescein diacetate (FDA) fluorescent assay [ 77 ].…”

The Local Neuropeptide System of Keratinocytes

“…In one study, analysis of microarray data demonstrated that cultured keratinocytes had a functional neuroendocrine machinery, and this was confirmed by testing the secretion of six neuroactive molecules by ELISA, namely α-MSH, β-endorphins, melatonin, substance P, cortisol, and neurotensin. Interestingly, hyaluronic acid regulated the production of several neuropeptides, including β-endorphins, in vitro [ 57 ]. Pro-enkephalins and met-enkephalin are also expressed in skin keratinocytes in vivo [ 58 ].…”