Developing biomarkers of healing and non-healing VLUs

开发愈合和非愈合 VLU 的生物标志物

• 批准号: 10786898
• 负责人: Ivan Jozic
• 金额: $ 37.15万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10786898
• 关键词: Aging; Alginates; Area; Biocompatible Materials; Biological Markers; Biology; Caring; Chronic; Classification; Clinical; Data; Detection; Development; Diabetic Foot Ulcer; Enrollment; Enzyme-Linked Immunosorbent Assay; Equipment; Exclusion; Exhibits; Exudate; Freezing; Functional disorder; Future; Health Professional; Healthcare Systems; Image; Leg Ulcer; Liquid substance; Location; Mass Spectrum Analysis; Measurement; Measures; Methodology; Methods; Methylcellulose; Molecular; Monitor; Outcome; Patient Care; Patients; Phase; Physiology; Population; Prognostic Marker; Proteins; Proteome; Proteomics; Protocols documentation; Recurrence; Reproducibility; Sample Size; Set protein; Source; Standardization; Sterile coverings; Testing; Time; Treatment outcome; Ulcer; Validation; Venous; Venous Insufficiency; Visit; acute wound; aggressive therapy; biomarker development; chronic ulcer; chronic wound; clinical care; clinically relevant; cost; detection method; diagnostic tool; digital; evidence base; healing; high dimensionality; improved; improved outcome; individualized medicine; insight; interest; molecular dynamics; novel marker; personalized approach; precision medicine; predict clinical outcome; predictive marker; product development; prognostic; prospective; protein biomarkers; real time monitoring; responders and non-responders; smart bandage; standard care; standard of care; tool; wound; wound bed; wound care; wound dressing; wound healing

Project Summary This project proposes to use wound fluid analyses captured from discarded wound dressings to develop biomarkers that can predict healing outcome and monitor healing progression of Venous Leg Ulcers (VLUs). VLUs represent a specific case of chronic ulcers occurring in the gaiter area in the setting of chronic venous insufficiency and account for about 70% of all chronic leg ulcers. Considering the aging of the population a concerning picture emerges: more ulcers occurring in sicker patients which are ever more expensive to treat. Despite recent advances, more than 50% of patients with VLUs fail to heal with standard care. One of the major obstacles to improving outcomes is the inability to predict early on who will and who will not respond to standard of care. Therefore, there is an urgent and unmet need to predict healing outcomes and to differentiate healing from non-healing VLUs. Due to dynamic molecular changes within the wound, its microenvironment can be tested and monitored, which offers an opportunity to obtain key information regarding the status of wound biology. Moreover, quantification of such molecular changes that reflect wound healing status would provide important tools that can guide treatment approach, directly impacting the clinical outcomes. Thus, both predictive and monitoring biomarkers are needed to enable prospective tailoring of therapies to efficiently: 1) maximize the treatment outcomes, 2) target more aggressive treatment to only those patients who need it and 3) develop personalized approaches to each VLU. In the initial discovery phase, we will enroll 30 VLU patients (10 healers and 20 non-healers) to identify a set of protein biomarkers that predict healing outcomes (Aim 1); those that can serve as monitoring biomarkers (Aim 2). We will extract wound fluid from discarded wound dressings and quantify proteins by using mass spectrometry (LC-MS/MS) and correlate them to healing outcomes at week 4. We have generated preliminary data that support feasibility of the overall approach and confirm that wound dressings (either analyzed in real time or stored frozen) of any type can be utilized for biomarker quantification. We have also identified spatially distinct localization of molecules at the center vs perimeter of the wound dressing, resulting in specific profiles that reflect the biology of the wound bed and wound edge respectively. This project will provide a unique opportunity to capitalize on easy access of discarded wound dressings as a source of wound biomaterial (exudate) that can serve for biomarker detection. It will not only identify and validate specific set of biomarkers that can predict healing outcome and/or monitor healing progression but will also provide streamlined method of detection that can be readily implemented.

项目摘要 该项目建议使用从丢弃的伤口敷料中捕获的伤口液分析来发展 可以预测愈合结果并监测静脉腿溃疡（VLU）的愈合进展的生物标志物。 VLU表示在慢性静脉 不足和约占所有慢性腿溃疡的70％。考虑人口的老龄化a 出现有关图片的出现：病人发生的溃疡更多，这些溃疡越来越昂贵。 尽管最近进步，但超过50％的VLU患者无法通过标准护理愈合。专业之一 改善结局的障碍是无法尽早预测谁的意愿，谁不会对标准做出反应 照顾。因此，紧急且未满足的需要预测治愈结果并区分治愈 来自非治疗vlus。由于伤口内动态分子变化，其微环境可以是 经过测试和监测，这提供了获得有关伤口状态的关键信息的机会 生物学。此外，反映伤口愈合状态的这种分子变化的量化将提供 可以指导治疗方法的重要工具，直接影响临床结果。因此，都预测 并且需要监测生物标志物以使疗法的前瞻性裁缝有效：1）最大化 治疗结果，2）仅针对需要它的患者进行更积极的治疗，3） 每个VLU的个性化方法。在最初的发现阶段，我们将注册30名VLU患者（10名治疗师 和20个非治疗者）确定一组预测愈合结果的蛋白质生物标志物（AIM 1）；那些可以 用作监测生物标志物（AIM 2）。我们将从废弃的伤口敷料中提取伤口液并进行量化 蛋白质使用质谱（LC-MS/MS），并将其与第4周的康复结果相关联。 生成的初步数据，这些数据支持整体方法的可行性并确认伤口敷料 （实时分析或储存的冷冻）可以用于生物标志物定量。我们有 还确定了在伤口敷料的中心与外围的分子在空间上不同的定位， 导致分别反映伤口床和伤口边缘的生物学的特定轮廓。这个项目 将提供一个独特的机会，以利用轻松获取废弃的伤口敷料作为来源 可用于生物标志物检测的伤口生物材料（渗出液）。它不仅会识别和验证特定 可以预测愈合结果和/或监测愈合进展的一组生物标志物，也将提供 简化的检测方法可以容易实施。