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Neutrophil Response to Tissue Templates in Vitro: Implant Implications

中性粒细胞对体外组织模板的反应：植入的影响

基本信息

批准号：
9232275
负责人：
Gary L Bowlin
金额：
$ 38.85万
依托单位：
UNIVERSITY OF MEMPHIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9232275
关键词：
Acute Air Architecture Bacteria Biomedical Research Blood Caliber Cell Line Cells Chemistry DNA Data Development Dimensions Disease Electrospinning Emigrations Event Failure Fiber Funding Gelatinase B Goals Growth Histone H4 Histones Human Immune Implant In Situ In Vitro Inflammation Inflammatory Inflammatory Response Injury Innate Immune Response Interdisciplinary Study Lead Matrix Metalloproteinases Modeling Molecular Motion Motivation Natural Immunity Natural regeneration Neutrophil Activation Neutrophil Infiltration Operative Surgical Procedures Organ Outcome Performance Phase Phenotype Physiological Polymers Population Preparation Process Rattus Research Role Site Stream Structure Surface Testing Thromboplastin Thrombosis Tissue Engineering Tissues Trauma United States National Institutes of Health Universities Vascular Graft angiogenesis base cell type cytokine design electric impedance extracellular graduate student granulocyte immunoreaction implantation improved in vivo interest killings macrophage monocyte neutrophil new growth pathogen preconditioning regenerative repaired response subcutaneous tissue regeneration undergraduate student

项目摘要

The proposal aims to examine the neutrophil response in terms of neutrophil extracellular trap (NET) formation (process known as NETosis) to three-dimensional regeneration templates with varying yet controlled architecture and composition. Templates will be fabricated by air- impedance electrospinning such that the resulting architectures vary in fiber diameter, pore size, and composition to create diverse microenvironments to allow examination of the role of each variable in regulating the NET formation and subsequent cellular interactions and responses to this preconditioning event. The overriding hypothesis is that an electrospun template architecture and composition will modulate the degree of NETosis such that this neutrophil preconditioning event would promote/enhance regeneration and reduce implant failure (i.e. acute thrombosis and enhanced inflammation/tissue destruction). More specifically, Aim 1 will define the role of template architecture and composition in modulating template-interacting neutrophil NETosis, and determine the subsequent in vitro role of this preconditioning event. Aim 2 will then determine the in vivo template invoked degree of neutrophil NETosis and thus test whether the in vitro results are correlative as well as the outcomes associated with the degree of NETosis-template preconditioning in a rat subcutaneous model. It is anticipated that increasing template fiber diameters/pore sizes and particular compositions will invoke a minimal degree of NETosis, leading to recruited neutrophil and macrophage phenotypes that secrete cytokines and MMPs that favor tissue regeneration. The ultimate goal is to be able to define a template architecture and composition that is capable of supporting an innate immunity cell line-instructed and enhanced regeneration upon implantation as initiated and/or directed by the template-interacting, microenvironment neutrophils to replace or repair damaged or diseased tissues and organs.

本研究旨在探讨中性粒细胞对细胞外陷阱的反应