Collaborative Research: An in vivo/in silico Approach to Delineate the Effect of Age on Pressure Ulcer Susceptibility

合作研究：描述年龄对压疮易感性影响的体内/计算机方法

基本信息

批准号：
1916663
负责人：
Manuel Rausch
金额：
$ 32.04万
依托单位：
University of Texas at Austin
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2023-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1916663&HistoricalAwards=false
关键词：
Collaborative Research vivo silico Approach

项目摘要

Pressure ulcers, or bed sores, are a debilitating condition that affects more than 3 million Americans. Today, it is understood that pressure ulcers follow from continued compression of skin in patients that have lost the ability to reposition themselves and relieve that pressure. For example, patients in wheel chairs or patients that have become bedridden frequently suffer from pressure ulcers. Patients of advanced age are particularly prone to pressure ulcers. While we understand the behavioral factors that may, in part, explain this increased incidence, the age-related anatomical and physiological factors that may contribute to increased risk in patients of advanced age have remained mostly unexplored and unknown. This knowledge is important, as it may provide a pathway to age-specific treatment strategies. This project will use a mouse model of pressure ulcer formation and progression to investigate these age-related anatomical and physiological factors and their contribution to the increased risk of pressure ulcers due to age. Furthermore, the research will integrate these results into a comprehensive computational model that will be a first step toward predicting pressure ulcers. With such a model it will be possible to not only design better support systems -- such as wheelchairs, mattresses, and prostheses -- but also to explore novel diagnostic technologies and therapeutic strategies. This project will integrate a diverse group of undergraduate students into the research, using peer mentoring approaches. Finally, and most importantly, in order to accelerate the transfer of knowledge from this study to the general public, educational podcasts on pressure ulcers will be designed that will be disseminated by integrating them into successful, long-running podcast series.The overall goal of this research is to quantify the effect of age on non-behavioral factors of pressure ulcer formation using mice as a biological model system in combination with a novel multi-scale, multi-physics computer model. This goal is supported by two objectives. The first will determine the non-behavior factors that increase the risk of pressure ulcer initiation in the elderly. Using young and old mice, the role of skin compliance in the microvascular collapse and ischemia that occurs prior to pressure ulcer will be investigated. The second objective is to determine the non-behavioral factors that increase the risk of pressure ulcer progression by looking at three contributory factors: ischemic injury, reperfusion injury, and mechanical injury. For both objectives, the experimental data will be integrated into a multi-scale, multi-physics model that will then be able to link matrix-cell and cell-cell signalling to pressure ulcer formation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

压疮或褥疮是一种使人衰弱的疾病，影响着超过 300 万美国人。如今，据了解，压疮是由于患者失去重新定位和缓解压力的能力而导致皮肤持续受压所致。例如，坐轮椅的患者或卧床不起的患者经常患有压疮。高龄患者特别容易出现压疮。虽然我们了解行为因素可能在一定程度上解释了这种发病率的增加，但可能导致高龄患者风险增加的与年龄相关的解剖和生理因素仍未被探索和未知。这些知识很重要，因为它可能提供针对特定年龄的治疗策略的途径。该项目将使用压疮形成和进展的小鼠模型来研究这些与年龄相关的解剖和生理因素及其对因年龄而增加的压疮风险的贡献。此外，该研究将把这些结果整合到一个综合的计算模型中，这将是预测压疮的第一步。有了这样的模型，不仅可以设计更好的支撑系统（例如轮椅、床垫和假肢），还可以探索新颖的诊断技术和治疗策略。该项目将使用同伴指导方法将不同的本科生群体整合到研究中。最后，也是最重要的，为了加速将本研究的知识转移给公众，将设计有关压疮的教育播客，并将其整合到成功的长期播客系列中进行传播。总体目标这项研究旨在利用小鼠作为生物模型系统并结合新型多尺度、多物理计算机模型来量化年龄对压力性溃疡形成的非行为因素的影响。这一目标由两个目标支持。第一个将确定增加老年人发生压疮风险的非行为因素。使用年轻和年老的小鼠，将研究皮肤顺应性在压疮之前发生的微血管塌陷和缺血中的作用。第二个目标是通过观察三个影响因素来确定增加压疮进展风险的非行为因素：缺血性损伤、再灌注损伤和机械性损伤。对于这两个目标，实验数据将被整合到一个多尺度、多物理模型中，然后能够将基质-细胞和细胞-细胞信号传导与压疮形成联系起来。该奖项反映了 NSF 的法定使命，并被视为值得通过使用基金会的智力优点和更广泛的影响审查标准进行评估来支持。