Bimodal platform for nondestructive analysis of engineered vascular biomaterials

用于工程血管生物材料无损分析的双模平台

• 批准号: 8883056
• 负责人: Leigh Gareth Griffiths
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8883056
• 关键词: Address; Age-Years; Applications Grants; Area; Atherosclerosis; Biochemical; Biocompatible Materials; Blood Vessels; Bone Marrow; Cardiac Surgery procedures; Cardiovascular Diseases; Carotid Arteries; Cattle; Cessation of life; Clinical; Computing Methodologies; Coronary heart disease; Data; Data Analyses; Defect; Development; Diagnostic; Engineering; Evaluation; Excision; Extracellular Matrix; Family suidae; Fluorescence; Fluorescence Spectroscopy; Frequencies; Health; Heterogeneity; Histologic; Image; Image Analysis; Imaging technology; Immunology procedure; Implant; In Vitro; Individual; Label; Laboratories; Measurement; Mechanics; Mesenchymal Stem Cells; Methods; Microscopy; Modeling; Monitor; Morphology; National Heart, Lung, and Blood Institute; Nature; Nonionizing Radiation; Optics; Patients; Peripheral arterial disease; Prevalence; Process; Production; Property; Quality of life; Research; Safety; Sampling; Scanning; Signal Transduction; Site; Solutions; Structure; Structure-Activity Relationship; Surface; System; Techniques; Technology; Testing; Time; Tissue Engineering; Tissues; Translations; Tubular formation; Ultrasonics; Ultrasonography; Validation; attenuation; base; clinical application; implantation; improved; in vivo; insight; instrumentation; novel diagnostics; novel therapeutics; optical imaging; optical spectra; pericardial sac; public health relevance; regenerative; scaffold; screening; spectroscopic imaging; statistics; tissue support frame; tool; vascular tissue engineering; working group

 DESCRIPTION (provided by applicant): The objective of this grant application is to research, test and validate a bi-modal diagnostic platform combining optical and ultrasound imaging technologies for real-time, non-destructive in-vitro and in-vivo analysis of composition, structure function and site specific cellular repopulation of extracellular matrix (ECM) scaffolds utilized fr vascular tissue engineering. The proposed approach has the potential to significantly advance the field of vascular tissue engineering and facilitate translation of engineered vascular material to clinical application. The non-destructive nature of the proposed platform enables repeated assessment of ECM scaffold and recellularized construct structure-function relationships both in-vitro and in-vivo. The proposed technology therefore alleviates the need for destructive analysis methods across multiple time points, which are costly, time consuming and frequently impractical. Moreover, the proposed technology will facilitate (a) in-vitro rapid screening of scaffold production methods and non-destructive assessment of batch quality; and (b) non- terminal in-vivo assessment across multiple time points, thereby providing mechanistic insights into engineered vascular tissue regenerative processes. The proposed bi-modal platform will integrate two non-ionizing radiation techniques for label-free tissue analysis: (1) Multispectral Time-Resolved Fluorescence Spectroscopy (TRFS) system for evaluation of ECM composition and biochemical heterogeneities of vascular biomaterials; and (2) High-frequency Ultrasound (US) imaging for evaluation of structural properties and morphology in vascular biomaterials. This is enabled by either Ultrasound Backscatter Microscopy (UBM) for planar scanning or conventional Intravascular Ultrasound (IVUS) for rotational scanning. Four specific aims will be addressed. Aim 1 is focused on developing a set of customized tools (instrumentation and data analysis methods) for in- vitro and in-vivo assessment of vascular scaffolds and constructs. Aim 2 in focused on demonstrating the feasibility of the bi-modal platform as a non-destructive tool for assessment of vascular scaffold properties. Aim 3 is focused on demonstrating the bi-modal platform's ability as a non-destructively tool for in-vitro studying and monitoring of vascular tissue construct formation. Aim 4 is focused on demonstrating the feasibility of the bi-modal technique as a non-destructive tool for monitoring the maturation of vascular constructs in-vivo post- implantation. In summary, the technology proposed for development and validation in this grant application offers a non-destructive solution for the evaluation of many important features (compositional, structural and functional) associated with the maturity and functionality of vascular biomaterials. This is likely to improve our ability to produce engineered vascular tissues in the laboratory for in-vivo implantation which can accelerate the integration time of the implant with the surrounding host tissue, thus restoring the desired quality of life to the patient. Emphasis will be placed on the evaluation of engineered vascular tissue, though, if successful, this non-destructive technique can be applied to assess a variety of engineered tissues.

 描述（由申请人提供）：本资助申请的目的是研究、测试和验证一种结合光学和超声成像技术的双模态诊断平台，用于实时、非破坏性的体外和体内分析用于血管组织工程的细胞外基质（ECM）支架的组成、结构功能和位点特异性细胞再增殖。所提出的方法有可能显着推进血管组织工程领域，并促进工程血管材料的临床应用。所提出的平台的非破坏性性质使得能够在体外和体内重复评估ECM支架和再细胞化构建体的结构-功能关系。因此，所提出的技术证实了对跨多个时间点的破坏性分析方法的需要，这些方法是昂贵的、耗时的并且经常是不切实际的。此外，所提出的技术将促进（a）支架生产方法的体外快速筛选和批次质量的非破坏性评估;和（B）跨多个时间点的非终末体内评估，从而提供对工程化血管组织再生过程的机理性见解。拟议的双模态平台将整合两种用于无标记组织分析的非电离辐射技术：（1）多光谱时间分辨荧光光谱（TRFS）系统，用于评价血管生物材料的ECM成分和生物化学异质性;（2）高频超声（US）成像，用于评价血管生物材料的结构特性和形态。这通过用于平面扫描的超声背向散射显微镜（UBM）或用于旋转扫描的常规血管内超声（IVUS）来实现。将讨论四个具体目标。目标1的重点是开发一套定制的工具（仪器和数据分析方法），用于血管支架和结构的体外和体内评估。目的2集中于证明双模式平台作为评估血管支架特性的非破坏性工具的可行性。目的3集中于证明双模态平台作为用于体外研究和监测血管组织构建体形成的非破坏性工具的能力。目的4的重点是证明双模式技术作为监测植入后体内血管结构成熟的非破坏性工具的可行性。总之，本授权申请中提出的开发和验证技术为评价与血管生物材料成熟度和功能相关的许多重要特征（成分、结构和功能）提供了一种非破坏性解决方案。这很可能提高我们生产工程血管组织的能力 其可以加速植入物的整合时间 与周围的宿主组织接触，从而恢复患者所需的生活质量。重点将放在工程血管组织的评价，虽然，如果成功的话，这种非破坏性的技术可以应用于评估各种工程组织。