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.

这个应用程序的总体目标是了解NETosis的机制，分泌的过程 中性粒细胞胞外陷阱（NET），纤维模板，并将这些知识应用于工程 新的纤维模板集中于急性NETosis程度的衰减。这种衰减将 在原位再生过程中限制边缘组织整合的任何限制是至关重要的。中央 本研究的假设是纤维模板可以通过结构和治疗来工程化， 化合物释放以减弱急性相互作用的中性粒细胞引起的NETosis的程度。目标1将利用 近场静电纺丝（NFES）来制造精确的正方形网格模板，使得纤维直径 和孔径是自变量（模板结构）测试中的刺激作用， 体外急性模板诱导NETosis。目的2将阐明NETosis机制诱导的 模板和开发基于纤维的复合释放载体作为架构的补充手段 设计用于减弱急性、模板诱导的NETosis并潜在地最小化NET诱导的纤维化。 最后，在目标3中，我们将确定中性粒细胞NETosis的体内模板调用程度，从而 测试体外结果是否与NETosis模板衰减程度相关， 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，本研究的预期结果和创新将阐明关键的结构变量 和治疗性化合物的递送，以允许 关键的三维组织整合，不受急性表面NET的阻碍。这些 然后预计结果将在不同程度上转化为其他聚合物纤维组织模板 用于推进模板诱导的组织工程和原位组织工程领域的组合物和设计 再生的治疗选择，为各种各样的疾病困扰我们的社会。