Biosimulation of vocal fold surgical injury

声带手术损伤的生物模拟

• 批准号: 8723149
• 负责人: Nicole Yee-Key Li-Jessen
• 金额: $ 14.1万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723149
• 关键词: Acute; Acute Liver Failure; Address; Affect; Area; Biological; Biological Markers; Biological Process; Blood specimen; Caring; Cell Differentiation process; Cells; Cicatrix; Clinical; Communication impairment; Complex; Computational Technique; Computer Simulation; Computers; Data; Development; Disease; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Fibroblasts; Flow Cytometry; Functional disorder; Future; Goals; Healed; High Performance Computing; Human; Immune; Immunohistochemistry; Individual; Inflammation; Inflammatory; Injury; Larynx; Measures; Medical; Medicine; Methods; Modeling; Molecular; Mucous Membrane; National Institute on Deafness and Other Communication Disorders; Necrosis; Nonlinear Dynamics; Operative Surgical Procedures; Pathogenesis; Pathway interactions; Patients; Pattern; Population; Prevention; Process; Rattus; Research Infrastructure; Research Personnel; Research Priority; Running; Science; Sepsis; Serum; Source; Speed; Staining method; Stains; Strategic Planning; Surgical Injuries; Systems Biology; Technology; Testing; Therapeutic; Time; Tissue Banks; Tissues; Translations; Traumatic Brain Injury; United States National Institutes of Health; Voice; Work; Wound Healing; base; clinical application; clinical decision-making; computing resources; cost; cytokine; healing; high end computer; improved; injured; innovation; insight; macrophage; models and simulation; neutrophil; programs; public health relevance; repaired; response; therapy outcome; tissue repair; tool; treatment response; vocal cord

DESCRIPTION (provided by applicant): Vocal fold injury engenders a complex inflammation and wound healing response in laryngeal mucosal tissue, which commonly leads to scarring. Because individual variability in the formation and treatment for vocal fold scarring is considerable, the clinical decision making process for medical management is daunting. The work proposed in this R03 application exploits a systems biology approach that combines experimental and computational techniques to develop a computational model to assist in understanding the inflammatory and healing process associated with vocal fold scarring. Such models have provided valuable insights into the pathophysiology at the individual level and suggested pathways for inflammation treatment and healing optimization that are patient-specific. The overarching goal is to generate a clinical tool that will ultimately aid clinicians i prescribing personalized treatment for patients with vocal fold injury. The development of such a clinical tool requires the collection of tissue-specific biological data. We will extend our preliminary computational model's infrastructure, based on the new vocal fold data, to enhance its biological representation. The specific aims of this application are: (1) to count immune and repair cells including neutrophils, macrophages, endothelial cells and fibroblasts in surgically injured rat vocal folds using flow cytometry, up to 4 weeks post injury; (2) to identify the cell source of a damage-associated molecular pattern molecule (DAMP) and measure the levels of the DAMP and cytokines in vocal fold tissue and blood serum from rats following vocal fold surgery using immunohistochemistry and enzyme-linked immunosorbent assay respectively, up to 4 weeks post injury; (3) to implement our existing computational model on a high performance computing platform with an expanded infrastructure through the addition of biological data.

描述（由申请人提供）：声带损伤会在喉粘膜组织中引起复杂的炎症和伤口愈合反应，这通常会导致疤痕形成。由于声带疤痕的形成和治疗的个体差异很大，因此医疗管理的临床决策过程是令人畏惧的。 R03 申请中提出的工作利用系统生物学方法，结合实验和计算技术来开发计算模型，以帮助理解与声带疤痕相关的炎症和愈合过程。这些模型为个体水平的病理生理学提供了宝贵的见解，并提出了针对患者特异性的炎症治疗和愈合优化的途径。总体目标是生成一种临床工具，最终帮助临床医生为声带损伤患者提供个性化治疗。 这种临床工具的开发需要收集组织特异性的生物学数据。我们将基于新的声带数据扩展我们初步计算模型的基础设施，以增强其生物表征。该应用的具体目的是：(1) 使用流式细胞术对手术损伤的大鼠声带中的免疫和修复细胞进行计数，包括中性粒细胞、巨噬细胞、内皮细胞和成纤维细胞，时间长达损伤后 4 周； (2) 鉴定损伤相关分子模式分子（DAMP）的细胞来源，并分别使用免疫组织化学和酶联免疫吸附测定法测量声带手术后大鼠声带组织和血清中 DAMP 和细胞因子的水平，直至损伤后 4 周； （3）通过添加生物数据，在具有扩展基础设施的高性能计算平台上实施我们现有的计算模型。