Downregulation of neutrophil extracellular traps by fibrous regeneration template design.

这个应用程序的总体目标是了解NETsis的机制，即分泌过程 中性粒细胞胞外陷阱(Net)，在纤维模板上，并将所获得的知识应用于工程师 新型纤维模板侧重于减轻急性网织红细胞沉着症的程度。这种衰减将 关键是在原位再生过程中限制边缘组织整合的任何限制。中环 这项研究的假设是，纤维模板可以通过建筑和治疗来设计 通过与中性粒细胞的剧烈相互作用，复合释放以减轻网织红细胞增多的程度。目标1将利用 近场电纺(NFES)制造精密的正方形网格模板，使纤维直径 和孔径大小是自变量(模板构型)中检验的刺激作用 体外、急性、模板诱导的蚊虫中毒。Aim 2将阐明NETsis的诱导机制 模板和开发以纤维为基础的化合物释放车，作为建筑的补充手段 旨在减轻急性、模板诱导的NETsis，并潜在地将网络诱导的纤维化降至最低。 最后，在目标3中，我们将确定中性粒细胞网织的体内模板调用程度，从而 检验体外结果是否与网织红细胞-模板衰减程度相关 一种大鼠皮下模型，体内验证，如果这转化为边缘组织整合增强的话。 总而言之，这项研究的预期结果和创新将阐明关键的结构变量 和治疗性化合物在纤维状、聚二氧杂环酮模板的精细化中的输送，以允许 关键的三维组织整合，不受急性、表面网的阻碍。这些 然后，预计结果将不同程度地转化为其他聚合物、纤维组织模板 促进模板诱导组织工程和原位组织工程领域发展的组合物和设计 对于困扰我们社会的各种疾病的治疗选择中的再生。

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.