Programming dendritic cells in concert with morphagen delivery for periodontal re

摘要 慢性炎症是牙周炎的主要组成部分，而一些组织工程和 已经确定了再生策略，这些策略可能能够逆转牙周炎的破坏性影响， 它们的效用可能受到慢性炎性关节炎的不利微环境特征的影响， 状态树突状细胞（DC）是免疫系统的导体，并且它们可以提供适当的免疫应答。 靶向操纵和重定向免疫应答，以提供非炎症和非破坏性的免疫应答。 当地环境。本申请基于这样的假设，即提供适当的 提示的时空呈现可以局部地控制DC激活，以使免疫应答偏向 向非炎性表型，并显着提高骨诱导的有效性， 同一物质系统所携带的分子。将使用以下一组来检验这一假设 具体目标：（1）将开发材料系统，以招募东道发展中国家，并促进它们的积极性， 非炎性表型，（2）检查招募和编程大量细胞的材料的能力， 致耐受性DC促进调节性T细胞分化并介导啮齿动物模型中的炎症 （3）编码BMP-2的质粒DNA将从抑制牙周炎的材料系统中递送， 炎症，以测试通过DC靶向减少炎症是否可以增强 诱导牙周炎模型牙槽骨再生的方法。成功完成 这些目标将提供新的材料，其功能是首先调节炎症驱动的 牙周病，然后积极促进再生后成功抑制炎症。我们 我设想这些研究所产生的材料和知识可以很容易地转化为新的材料 用于引导组织再生（GTR），主动调节局部免疫和组织重建细胞群 在原地。更广泛地说，炎症是牙科和医学中许多其他临床挑战的组成部分， 在这个项目中所采用的一般策略在治疗这些疾病中有广泛的用途 以炎症介导的组织破坏为特征。此外，材料系统也可能 为探索DC运输、活化、T细胞分化和细胞周期的基础研究提供了新的有用工具。 免疫系统与炎症的关系

ABSTRACT Chronic inflammation is a major component of periodontitis, and while several tissue engineering and regeneration strategies have been identified that may be able to reverse the destructive effects of periodontitis their utility is likely compromised by the hostile microenvironment characteristic of the chronic inflammatory state. Dendritic cells (DCs) are the conductors of the immune system, and they may provide an appropriate target to manipulate and redirect the immune response to provide a non-inflammatory and non-destructive local environment. This application is based on the hypothesis that a material system providing appropriate spatiotemporal presentation of cues can locally control DC activation in order to bias the immune response towards a non-inflammatory phenotype, and dramatically enhance the effectiveness of bone inducing molecules carried by the same material system. This hypothesis will be examined with the following set of specific aims: (1) Materials systems will be developed to recruit host DCs and promote their activation towards a non-inflammatory phenotype, (2) Examine the ability of materials that recruit and program large numbers of tolerogenic DCs to promote regulatory T-cell differentiation and mediate inflammation in rodent models of periodontitis, and (3) Plasmid DNA encoding BMP-2 will be delivered from the material system that suppresses inflammation, to test whether reducing inflammation via DC targeting can enhance the effectiveness of inductive approaches to regenerate alveolar bone in rodent models of periodontitis. Successful completion of these aims will provide new materials that function to first modulate the inflammation-driven progression of periodontal disease, and then actively promote regeneration after successful suppression of inflammation. We envision the material and knowledge resulting from these studies can readily be translated into new materials for guided tissue regeneration (GTR) that actively regulate local immune and tissue rebuilding cell populations in situ. More broadly, inflammation is a component of many other clinical challenges in dentistry and medicine, and the general strategy pursued in this project could have wide utility in treating many of these diseases characterized by inflammation-mediated tissue destruction. Further, the material systems are also likely to provide novel and useful tools for basic studies probing DC trafficking, activation, T-cell differentiation, and the relation between the immune system and inflammation.