Engineered 3D Periodontal Tissue Constructs for Defining Functional Outcomes of Regenerative Processes

用于定义再生过程功能结果的工程 3D 牙周组织结构

基本信息

批准号：
10038285
负责人：
TRACY E POPOWICS
金额：
$ 17.65万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10038285
关键词：
3-Dimensional Actins Affect Age Age-Years Architecture Biomedical Engineering CD44 gene Catabolic Process Cell physiology Cells Clinical Collagen Collagen Fibril Complex Dental Cementum Dental Plaque Engineering Environment Future Gene Expression Goals Harvest Health Homeostasis Hyaluronan Hyaluronidase In Situ In Vitro Individual Inflammation Inflammation Mediators Inflammatory Inflammatory Response Knowledge Laboratories Link Longevity Manuals Measures Mechanics Mediating Modeling Myosin ATPase Natural regeneration Oligosaccharides Oral Outcome Pathway interactions Periodontal Diseases Periodontal Ligament Periodontitis Physiological Pilot Projects Play Population Process Regulation Research Risk Role Signal Pathway Signal Transduction Silicones Systemic disease TLR4 gene TNF gene Techniques Testing Time Tissues Tooth structure Traction Western Blotting Work age related aging population bone clinical development dexterity enzyme activity functional outcomes inflammatory milieu inhibitor/antagonist novel oral care preservation receptor receptor binding regenerative rho technique development tool

3-Dimensional Actins Affect Age Age-Years Architecture Biomedical Engineering CD44 gene Catabolic Process Cell physiology Cells Clinical Collagen Collagen Fibril Complex Dental Cementum Dental Plaque Engineering Environment Future Gene Expression Goals Harvest Health Homeostasis Hyaluronan Hyaluronidase In Situ In Vitro Individual Inflammation Inflammation Mediators Inflammatory Inflammatory Response Knowledge Laboratories Link Longevity Manuals Measures Mechanics Mediating Modeling Myosin ATPase Natural regeneration Oligosaccharides Oral Outcome Pathway interactions Periodontal Diseases Periodontal Ligament Periodontitis Physiological Pilot Projects Play Population Process Regulation Research Risk Role Signal Pathway Signal Transduction Silicones Systemic disease TLR4 gene TNF gene Techniques Testing Time Tissues Tooth structure Traction Western Blotting Work age related aging population bone clinical development dexterity enzyme activity functional outcomes inflammatory milieu inhibitor/antagonist novel oral care preservation receptor receptor binding regenerative rho technique development tool

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项目摘要

Project Summary. Knowledge of the effects of inflammation on the regenerative functions of periodontal ligament (PDL) cells is incomplete. This limits the development of techniques for periodontal regeneration that will maintain functional tooth support over the long term. Periodontal regeneration includes multiple cellular processes and a less understood component of these processes is PDL cell contractility. Cellular contractile forces are critical to the alignment of collagen fibrils that strengthen periodontal tissue and maintain its functional integrity. The long-term goal of this research is to identify mechanisms regulating PDL cell mechanics that can be used as clinical tools for regenerating and maintaining the architecture and function of the periodontal complex over time. Thus, the objective of this proposal is to demonstrate links between mechanisms regulating PDL cell contractile forces in proinflammatory microenvironments with PDL architecture and tissue mechanics. The central hypothesis of this proposal is that the inflammatory microenvironment regulates PDL cell contractile forces with effects on PDL tissue architecture and mechanics. This hypothesis will be tested in Specific Aim 1 through identification of mechanisms that regulate in vitro PDL cell contractile forces within proinflammatory microenvironments at the single-cell level. Western blots will be used to determine effects of tumor necrosis factor alpha (TNF) and hyaluronan oligosaccharide (oHA) on signaling pathways that generate cellular contractile force, such as the Rho/Rock pathway. In order to link the inflammatory environment and cell signaling with contractility, cellular traction forces will be measured with and without inflammatory mediators and signaling pathway inhibitors. In Specific Aim 2, three-dimensional PDL constructs will be developed to link the signaling pathways that regulate tissue-level contractility with matrix architecture and stiffness. Engineered PDL constructs will be developed using PDL cells and collagen and in situ forces will be measured. PDL constructs will be treated with stimulants and inhibitors of the Rho/Rock pathway under conditions that model periodontal homeostasis and inflammation. The successful completion of these aims will contribute to the development of clinical techniques for maintaining the PDL or regenerated tissues in a proinflammatory environment. Future research will expand this model to include cementum-like tissue and bone; thus, this pilot study is an initial step toward the future goal of regenerating the periodontal complex and maintaining its functional integrity over the long-term.

项目摘要。了解炎症对再生功能的影响牙周韧带（PDL）细胞不完整。这限制了技术的发展牙周再生将在长期内维持功能性牙齿支撑。牙周再生包括多个蜂窝过程和较少了解的组件这些过程是PDL细胞收缩性。细胞收缩力对胶原蛋白原纤维的对齐，以增强牙周组织并保持其功能正直。这项研究的长期目标是确定调节PDL细胞的机制可以用作再生和维护体系结构的临床工具的力学随着时间的推移，牙周复合物的功能。那是该提议的目的是演示调查PDL细胞收缩力的机制之间的联系具有PDL结构和组织力学的促炎性微环境。中央该提议的假设是炎性微环境调节PDL细胞收缩力对PDL组织结构和力学作用。这个假设将是通过鉴定调节体外PDL细胞的机制在特定目标1中测试单细胞水平的促炎性微环境内的收缩力。西印迹将用于确定肿瘤坏死因子α（TNF）和透明质酸的影响在产生细胞收缩力的信号通路上的寡糖（OHA），例如 Rho/Rock Pathway。为了将炎症环境和细胞信号与收缩力，细胞牵引力将在有或没有炎症介质的情况下测量和信号通路抑制剂。在特定的目标2中，三维PDL构建体将是开发以连接调节组织级收缩力与矩阵的信号通路建筑和僵硬。设计的PDL构建体将使用PDL单元格开发将测量胶原蛋白和原位力。 PDL构建体将用兴奋剂和在模拟牙周稳态的条件下，Rho/Rock途径的抑制剂炎。这些目标的成功完成将有助于发展在促炎性中维持PDL或再生组织的临床技术环境。未来的研究将扩大该模型，包括牙骨质样组织和骨头。这项试点研究是朝着再生牙周重新生成的未来目标的第一步长期复杂并保持其功能完整性。