Developing strategies for effective debridement in patients for venous leg ulcers

项目摘要 这项研究的目标是使用基因和蛋白质表达模式来开发护理点诊断 该工具可作为指导工具，优化无法愈合的静脉性小腿溃疡(VLU)的清创。 因此，它将确定客观和可靠的生物标记物，指导伤口从业者进行知情 决定何时伤口边缘清创是适当的。我们已经证明了从非 VLU清创前、后愈合缘形态明显，基因差异有统计学意义 蛋白质表达模式。清创前边缘活检产生的细胞显示不能愈合 迁移丧失和对生长因子的反应能力丧失所证明的表型，暗示丧失 而从清创后活检中获得的细胞是偏头痛的，并对 增长因素。一些临床数据显示，VLUS伤口缩小对创伤后有积极反应 床上清理剂。然而，伤口床清创并不总是被认为是VLU的标准护理。 因此，我们的目标是比较两种治疗方法的有效性：护理标准(即按压 治疗)和伤口床清创术与标准护理相结合。干预臂将由两个人组成 亚组，a)使用基因/蛋白质表达引导的清创方案，以及b)使用标准 VLU的临床清创方案。我们假设可以利用基因/蛋白质的表达模式 以指导VLU的伤口边缘清创，并进一步证明这种生物标记物引导的清创将得到改善 慢性无法愈合的VLU患者的愈合结果。此外，根据我们计划的基因组图谱 开发基于聚合酶链式反应和免疫染色的特异性方法，作为一种简化的诊断测试，以指导 清创程度。因此，我们将进行随机临床试验，以测试基因表达模式是否可以 可作为清创范围的指导工具，用于检验创缘清创的效果。 愈合进展(目标1)和发展基于聚合酶链式反应和/或免疫染色的补充评估 方法并验证其用于指导外科清创手术(目标2)。我们将继续进行基因组图谱和 比较清创前后标本的基因表达模式。下一步，表达式 模式将与愈合结果相关，将患者与进展为愈合的伤口进行比较 而那些在干预后4周没有出现症状的患者。这项拟议的研究是将 基因/蛋白质创伤信号作为临床工具。这项研究的成功完成将提供客观的 用于指导VLU患者伤口边缘清创的生物标记物。成立为法团 分子工具进入干预武器库将导致一种范式转变，这将改变治愈的过程， 降低发病率、死亡率，并降低相关治疗成本。

Project Summary The goal of this research is to use gene and protein expression patterns to develop point of care diagnostic tool that can serve as a guiding tool to optimize debridement for non-healing venous leg ulcers (VLUs). Thus, it will identify objective and reliable biomarkers that will guide wound practitioners to make informed decision when wound edge debridement is adequate. We have shown that biopsies obtained from the non- healing edges of VLUs before/after debridement have distinct morphologies and distinguishable gene and protein expression patterns. Cells generated from pre-debridement edge biopsies exhibit a non-healing phenotype as evidenced by loss of migration and loss of ability to respond to growth factors, suggesting a loss of healing potential whereas cells genrated from post-debridement biopsy are migratiory and responsive to growth factors. Some clinical data show a positive response in VLUs wound size reduction following wound bed debridemet. However, wound bed debridement is not always considered standard of care for VLUs. Therefore we aim to compare effectivnes of two therapeutic approaches: standard of care (i.e. compression therapy) and wound bed debridement coupled to standard of care. The intervention arm will consit of two subgroups, a) one that utilizes gene/protein expression-guidaded debridement protocol, and b) uses standard clinical debridement protocol for VLUs. We hypothesize that gene/protein expression patterns can be utilized to guide wound edge debridement in VLUs and further that such biomarker-guided debridement will improve healing outcome in patients suffering from chronic non-healing VLUs. Also, based on genomic profiles we plan to develop specific PCR- and immunostain-based methods to serve as a simplified diagnostic test to guide the extent of debridment. Thus, we will conduct a randomized clinical trial to test if gene expression patterns can be utilized as a guiding tool for the debridement extent and to test the effect of wound edge debridement on healing progression (Aim 1) and develop PCR- and/or immunostain-based complementary assessment method and validate it for guiding surgical debridement (Aim 2). We will proceed with genomic profiling and compare gene expression patterns of specimens obtained before and after debridement. Next, expression patterns will be correlated with healing outcomes comparing patients with wounds that progressed to healing with those that did not at 4 weeks post intervention. The proposed study is the first step in incorporating gene/protein wound signatures as a clinical tool. Successful completion of this study will provide objective biological markers to guide wound edge debridement in patients suffering from VLUs. Incorporation of molecular tools into armory of intervention will result in a paradigm shift that will alter the course of healing, decrease morbidity, mortality, and lower associated treatment costs.