Downregulation of neutrophil extracellular traps by fibrous regeneration template design.

通过纤维再生模板设计下调中性粒细胞胞外陷阱。

• 批准号: 10654151
• 负责人: Gary L Bowlin
• 金额: $ 41.48万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654151
• 关键词: 3-Dimensional; Acute; Architecture; Attenuated; Automobile Driving; Biocompatible Materials; Biomedical Research; Characteristics; Data; Development; Diameter; Disease; Down-Regulation; Electrospinning; Engineering; Fiber; Fibrosis; Funding; Immune response; Implant; In Situ; In Vitro; Injury; Innate Immune System; Knowledge; Modeling; Natural regeneration; Operative Surgical Procedures; Outcome; Performance; Pharmaceutical Preparations; Play; Polymers; Porosity; Process; Rattus; Regenerative capacity; Regulation; Research; Role; Site; Societies; Structure; Surface; Testing; Therapeutic; Tissue Engineering; Tissues; Translating; United States National Institutes of Health; Universities; Vascular Graft; Work; attenuation; delivery vehicle; design; extracellular; first responder; graduate student; implantation; improved; in vivo; innovation; knowledge base; neutrophil; next generation; novel; response; secretion process; subcutaneous; tissue regeneration; undergraduate student

This application's overall objective is to understand the mechanisms of NETosis, the process of secreting neutrophil extracellular traps (NETs), on fibrous templates and to apply this knowledge gained to engineer novel fibrous templates focused on the attenuation of the degree of acute NETosis. This attenuation will be critical to limit any restriction of marginal tissue integration during in situ regeneration. The central hypothesis of this study is that fibrous templates can be engineered via architecture and therapeutic compound release to attenuate the degree of NETosis by acutely interacting neutrophils. Aim 1 will utilize near-field electrospinning (NFES) to fabricate precision, square-grid templates such that fiber diameter and pore size are the independent variables (template architecture) tested in the role of stimulating in vitro, acute, template-induced NETosis. Aim 2 will elucidate NETosis mechanisms induced by the templates and develop fiber-based, compound releasing vehicles as a supplemental means to architecture design to attenuate acute, template-induced NETosis and potentially minimize NET-induced fibrosis. Finally, in Aim 3, we will determine the in vivo template invoked degree of neutrophil NETosis and thus test whether the in vitro results are correlative in terms of the degree of NETosis-template attenuation in a rat subcutaneous model, in vivo veritas, and if this translates to enhanced marginal tissue integration. In summary, this study's expected outcome and innovation will elucidate the critical structural variables and therapeutic compound delivery in the refinement of fibrous, polydioxanone templates to allow for critical three-dimensional tissue integration, free from the impediment of acute, surface NETs. These results are then expected to translate to various degrees to other polymeric, fibrous tissue template compositions and designs to advance the field of template-induced tissue engineering and in situ regeneration in the treatment options for a wide variety of disorders plaguing our society.

该应用程序的总体目标是了解Netosis的机制，即分泌的过程 中性粒细胞外陷阱（网），纤维模板上，并将这些知识应用于工程师 新型纤维模板的重点是急性肠病的衰减。这种衰减会 至关重要的是限制原位再生期间边缘组织整合的任何限制。中央 这项研究的假设是纤维模板可以通过结构和治疗性进行设计 化合物释放可通过急性相互作用的中性粒细胞减弱脂肪生命程度。 AIM 1将使用 近场静电纺丝（NFES）以制造精度，方格模板，使纤维直径 孔径和孔径是在刺激中测试的自变量（模板结构） 体外，急性，模板诱导的肠病。 AIM 2将阐明由 模板并开发基于纤维的复合释放车辆作为建筑的补充手段 设计可减弱急性，模板诱导的肠病，并可能最大程度地减少网络诱导的纤维化。 最后，在AIM 3中，我们将确定中性粒细胞增生的体内模板，从而调用的程度 测试体外结果是否与Netosis-Tplate衰减程度相关 大鼠皮下模型，体内Veritas，如果这转化为增强的边缘组织整合。 总之，这项研究的预期结果和创新将阐明关键的结构变量 和治疗化合物递送在纤维，聚二甲酮模板的细化中，以允许 临界三维组织整合，没有急性，表面网的障碍。这些 然后，结果预计将转化为各种程度，转换为其他聚合物，纤维组织模板 组成和设计，以推进模板诱导的组织工程领域和原位 在困扰我们社会的各种疾病的治疗方案中的再生。