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 Mw lot showed a pseoudoplastic behaviour with a zero-shear viscosity (η0) 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.

中文翻译：

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生物物理学定义的透明质酸基化合物可加速迁移并刺激角质形成细胞衍生的神经调节剂的产生。

透明质酸（HA）制剂已广泛用于临床实践，最新数据表明，市售的基于HA的化合物可促进溃疡再上皮形成并减轻疼痛。但是，这些作用的病理生理基础仍然知之甚少。在本研究中，我们研究了HA制剂与一系列胶原前体合成氨基酸（即L-脯氨酸，L-亮氨酸，L-赖氨酸和甘氨酸）结合的生物物理，生物分子和功能特性。通过尺寸排阻色谱-三重检测器阵列（SEC-TDA）对Aminogam®进行流体动力学表征，发现平均分子量为700-1700 kDa。1700kDa Mw批次的流变学测量显示了拟塑性行为，其零剪切粘度（η0）在25°C时为90±9 Pa∙s，在37°C时为55±6 Pa∙s。在无成纤维细胞的系统中进行的自动延时视频显微镜研究表明，1％（v / v）的Aminogam®可以显着减少受伤的角质形成细胞单层的愈合时间。在AKGOS分析中，Aminogam®刺激了角质形成细胞的细胞运动（趋化）和定向迁移（趋化）。对微阵列数据的分析表明，角质形成细胞具有功能性神经内分泌机制，并通过ELISA测试了六个神经活性分子的分泌得到了证实，这些分子即α-MSH，β-内啡肽，褪黑激素，P物质，皮质醇和神经降压素。有趣的是，Aminogam®调节了包括β-内啡肽在内的几种神经肽的产生。