Intravital imaging of nanofiber-mediated skeletal repair

纳米纤维介导的骨骼修复的活体成像

• 批准号: 8030048
• 负责人: XINPING ZHANG
• 金额: $ 23.12万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-04 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8030048
• 关键词: Address; Animal Model; Animals; Binding; Biochemical; Biological Assay; Biomimetics; Blood Vessels; Bone Marrow; Bone Regeneration; Bone Tissue; Caliber; Calvaria; Cells; Cephalic; Clinical; Complex; Defect; Detection; Dextrans; Differentiation and Growth; Engineering; Evaluation; Extracellular Matrix; Fluorescence; Funding; Generations; Healed; Image; Image Analysis; Imagery; Imaging technology; Impaired wound healing; Implant; In Vitro; Indium; Institutes; Laser Scanning Microscopy; Life; Mediating; Mesenchymal Stem Cells; Modality; Modeling; Molecular; Monitor; Morphology; Mus; Natural regeneration; Osseointegration; Osteogenesis; Patients; Production; Property; Proteins; Protocols documentation; Qualitative Evaluations; Quantitative Evaluations; Research; Resolution; Risk; Role; Series; Signal Transduction; Stem cells; System; Techniques; Technology; Testing; Texas; Therapeutic; Time; Tissue Engineering; Tissues; Transgenic Animals; Transgenic Mice; Translational Research; Universities; Wound Healing; base; bone; bone healing; cell motility; design; dextran; efficacy testing; flexibility; healing; imaging modality; improved; in vivo; intravenous injection; intravital microscopy; magnetic field; nanofiber; regenerative; repaired; scaffold; second harmonic; skeletal; spatial relationship; stem cell niche; success; tissue regeneration; tool

DESCRIPTION (provided by applicant): Current studies to elucidate the functional significance of the nanofiber-based tissue engineering construct in a complex in vivo bone healing microenvironment are limited due to the lack of an appropriate in vivo bone healing model that permits dynamic and high-resolution analysis. To overcome this limitation, we propose to develop a multiphoton laser-scanning microscopy (MPLSM)- based intravital imaging modality that permits dynamic and longitudinal imaging analyses of nanofiber-based tissue engineering constructs. We will develop a calvarial defect window chamber model in mice, which allows intravital microscopy to monitor the cellular constructs in time-lapse imaging series and in real-time functional analysis. Within the proposed two-year funding period, we will establish a reproducible in vivo assay system with defined imaging analysis protocols for quantitative and qualitative evaluation of the bone regenerative properties of the nanofibrous scaffold. The proposal will center on three important design considerations to address nanofiber-mediated repair: ECM organization, cell migration and vascular ingrowth. Our current proposal represents the first attempt to establish such an in vivo assay system to address the role of nanofibers in a complex in vivo healing microenvironment. The success of the proposed study not only could provide a useful tool for the optimization of nanofibrous-based tissue engineering construct, but also potentially offer a biomimetic flexible construct to treat patients with impaired healing. The success of this system could open up experimental evaluation of specific mechanisms for cell-based bone regeneration, further offering an experimental testing modality for therapeutic strategies. PUBLIC HEALTH RELEVANCE: Nanofiber holds great promise in tissue repair and regeneration due to its versatility in creating an integrated platform for stem cell manipulations. The project will use state-of- the-art imaging technology to define the important elements in the design of nanofibers for bone repair and regeneration.

描述（由申请人提供）：由于缺乏适当的体内骨愈合模型，允许动态和高分辨率分析，目前阐明纳米纤维为基础的组织工程结构在复杂体内骨愈合微环境中的功能意义的研究受到限制。为了克服这一限制，我们建议开发一种基于多光子激光扫描显微镜（MPLSM）的活体成像模式，允许对基于纳米纤维的组织工程结构进行动态和纵向成像分析。我们将开发一个小鼠颅骨缺损窗室模型，该模型允许活体显微镜在延时成像系列和实时功能分析中监测细胞结构。在拟议的两年资助期内，我们将建立一个可重复的体内分析系统，具有明确的成像分析方案，用于定量和定性评估纳米纤维支架的骨再生特性。该提案将集中在三个重要的设计考虑，以解决纳米纤维介导的修复：ECM组织，细胞迁移和血管长入。我们目前的提议是首次尝试建立这样一个体内分析系统，以解决纳米纤维在复杂的体内愈合微环境中的作用。该研究的成功不仅可以为纳米纤维组织工程结构的优化提供有用的工具，而且还可能为治疗愈合受损患者提供仿生柔性结构。该系统的成功可以为细胞骨再生的特定机制提供实验评估，进一步为治疗策略提供实验测试模式。