Biosimulation of vocal fold surgical injury

声带手术损伤的生物模拟

• 批准号: 8523826
• 负责人: Nicole Yee-Key Li-Jessen
• 金额: $ 13.4万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523826
• 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（由申请方提供）：声带损伤在喉粘膜组织中产生复杂的炎症和伤口愈合反应，通常导致瘢痕形成。由于声带瘢痕形成和治疗的个体差异是相当大的，临床决策过程中的医疗管理是令人生畏的。 R 03申请中提出的工作利用了一种系统生物学方法，该方法结合了实验和计算技术来开发计算模型，以帮助理解与声带瘢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有价值的见解，并为患者特异性的炎症治疗和愈合优化提供了建议。总体目标是生成一个临床工具，最终帮助临床医生为声带损伤患者开出个性化治疗处方。 这种临床工具的开发需要收集组织特异性生物数据。我们将扩展我们的初步计算模型的基础设施，新的声带数据的基础上，以提高其生物表示。本申请的具体目的是：（1）使用流式细胞术计数手术损伤的大鼠声带中的免疫和修复细胞，包括中性粒细胞、巨噬细胞、内皮细胞和成纤维细胞，直至损伤后4周;（2）鉴定损伤相关分子模式分子（DAMP）的细胞来源分别采用免疫组化和酶联免疫吸附法检测声带手术后4周大鼠声带组织和血清中DAMP和细胞因子的水平;（3）在一个高性能的计算平台上实施我们现有的计算模型，并通过增加生物数据来扩展基础设施。