Abstract：
Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.
摘要：
未愈合伤口的分泌物含有致病性的驱动因素。我们利用了超过800个来自不同病因的非愈合和愈合伤口的分泌物，通过三种不同的方法收集，为了发展特定的伤口，基于细胞的功能生物标志物测定。人真皮成纤维细胞增殖用作a）的读数，以区分愈合和不愈合的伤口，b)跟踪个体患者的愈合过程，和c)评估治疗剂对慢性伤口的离体效果。我们观察到伤口慢性与个体渗出物对成纤维细胞增殖的抑制作用之间存在很强的相关性，具有良好的诊断灵敏度(76-90%，取决于样品收集方法)。临床上的非愈合向愈合表型的转变恢复成纤维细胞增殖和细胞外基质形成,同时减少炎性细胞因子产生。暴露于离体非愈合伤口渗出物的成纤维细胞的转录分析显示了炎性细胞因子和趋化因子途径的诱导以及未折叠的蛋白质反应。表明这些变化可能导致不愈合伤口的病理。测试伤口治疗剂血小板衍生的生长因子和磺胺嘧啶银产生了符合临床经验的反应，并表明该测定对寻找和分析新疗法的有用性。
