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

压疮或床疮是一种使人虚弱的疾病，影响着300多万美国人。今天，人们了解到，压疮是由于失去了重新定位和缓解压力的能力的患者的皮肤持续受到压迫而导致的。例如，坐在轮椅上的病人或卧床不起的病人经常患有压疮。高龄患者特别容易发生压疮。虽然我们了解可能部分解释这种发病率增加的行为因素，但可能导致高龄患者风险增加的与年龄相关的解剖学和生理学因素大多仍未被探索和了解。这一知识很重要，因为它可能提供一条通向特定年龄治疗策略的途径。本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，这项研究将把这些结果整合到一个全面的计算模型中，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持系统--如轮椅、床垫和假肢--而且还可以探索新的诊断技术和治疗策略。这个项目将利用同伴指导的方法，将一群不同的本科生纳入研究。最后，也是最重要的是，为了加速从这项研究向公众传递知识，将设计关于压疮的教育播客，并将其整合到成功的、长期运行的播客系列中进行传播。本研究的总体目标是以小鼠为生物模型系统，结合新的多尺度、多物理的计算机模型，量化年龄对压疮形成的非行为因素的影响。这一目标得到两个目标的支持。第一项研究将确定增加老年人压疮发病风险的非行为因素。使用年轻和老年小鼠，皮肤顺应性在压疮前发生的微血管崩溃和缺血中的作用将被调查。第二个目标是通过观察三个因素来确定增加压疮进展风险的非行为因素：缺血损伤、再灌注损伤和机械损伤。对于这两个目标，实验数据将被整合到一个多尺度、多物理的模型中，然后该模型将能够将基质-细胞和细胞-细胞信号与压疮形成联系起来。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.