Noninvasive Monitoring of Tissue-engineered Constructs by US Elasticity Imaging

通过美国弹性成像对组织工程构建体进行无创监测

• 批准号: 8093116
• 负责人: KANG KIM
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8093116
• 关键词: Abdomen; Address; Animal Euthanasia; Animal Model; Animals; Architecture; Area; Biocompatible Materials; Cells; Characteristics; Clinic; Clinical; Data; Development; Elasticity; Elastin; Evaluation; Extracellular Matrix; Feedback; Functional Imaging; Goals; Growth; Histology; Histopathology; Image; Imaging Device; Imaging Techniques; Implant; In Situ; In Vitro; Influentials; Knowledge; Laboratories; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Methods; Modality; Modeling; Monitor; Natural regeneration; Organ; Performance; Phase; Polyurethanes; Procedures; Process; Property; Rattus; Regenerative Medicine; Research; Resolution; Sampling; Shapes; Specimen; Structure; Supporting Cell; Surface Properties; System; Techniques; Time; Tissue Engineering; Tissues; Translating; Translations; Ultrasonography; Weight; Work; X-Ray Computed Tomography; base; biodegradable polymer; cell growth; clinical application; clinical practice; design; human subject; imaging modality; improved; in vitro testing; in vivo; innovation; novel; programs; repaired; research study; scaffold; soft tissue; tissue regeneration; tissue support frame; tool

DESCRIPTION (provided by applicant): Non-invasively monitoring the extent of tissue scaffold degradation, cellular growth, and tissue development will greatly help tissue engineers to non-destructively evaluate candidate scaffold performance in vivo. Biodegradable polymer scaffolds are used to support cells and growing tissues until they are replaced by the body's own extracellular matrix (ECM). Two main challenges in creating the ideal biodegradable polymer scaffold are: (1) the scaffold must have a defined shape and porous internal architecture suitable for direct tissue ingrowths but with appropriate mechanical and degradation properties and (2) the scaffold must have the right surface properties to provide favorable conditions for cells to attach differentiate and lay down ECM. To design scaffolds which appropriately transfer their mechanical load over time to the in growing tissue, temporal data are required that verify the mechanical viability of the remodeling construct. Current analysis methods are destructive, requiring animal euthanasia and explanting the construct for histological and direct mechanical characterization. In addition, different samples are prepared and measured at varying times, but high growth deviation between specimens makes analysis difficult. Ideally, tissue engineers need a system that can non-invasively monitor growth in the same specimen over time. Other imaging methods, such as magnetic resonance imaging (MRI) and computed tomography (CT), provide internal scaffold structural information, but they are limited to providing only morphological information. Ultrasound easticity imaging (UEI) based on phase-sensitive speckle tracking can characterize the mechanical, structural, and functional change of the implanted engineered tissues at very high resolution and sensitivity. Local UEI offers the potential to radically improve the biomaterial scaffold design and engineered tissue growth techniques. The long term goal of this research program is to develop a novel noninvasive functional imaging modality in the field of tissue engineering and regenerative medicine. The objective of the current project is to evaluate UEI as noninvasive imaging tool to assess mechanical, structural, and functional characteristics of the scaffold degradation and tissue ingrowth. The specific aims are: (1) Establish the in vitro relationship between noninvasive UEI and the mechanical and structural characteristics of the biomaterial scaffold degradation. (2) Establish the in vivo relationship between noninvasive UEI and the mechanical, structural, and functional characteristics of simultaneous tissue growing and scaffold degradation. These specific aims will be evaluated using novel polyurethane-based soft tissue scaffolds with three different degradation rates. In-vivo feasibility will also be demonstrated using the rat abdominal repair model. If successful, UEI integrated into a commercial ultrasound scanner can also be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained conveniently and non-invasively from human subjects PUBLIC HEALTH RELEVANCE: Tissue Engineering is an emerging, interdisciplinary field which is full of promise for those in need of organ and tissue replacement and repair. However, some major limitations with the development and translation remained unsolved mainly due to the limitations of laboratory feedback capabilities, especially non-invasive assessment tool for the implants in animal study. Clinical application of tissue engineering treatments will also require the ability to non-invasively monitor functional tissue regeneration. The proposed ultrasound elasticity imaging technique will provide quantitative assessment and monitoring of the mechanical strength of the engineered tissue as it grows into the native tissue. This technique can be easily integrated into a commercial ultrasound scanner for real-time in-vivo animal study, significantly reducing the number of animals required in the study, and eventually as a clinical tool to monitor the tissue engineering treatments.

描述（由申请人提供）：非侵入性监测组织支架降解，细胞生长和组织发育的程度将极大地帮助组织工程师在体内无损地评估候选型支架的性能。可生物降解的聚合物支架用于支撑细胞和生长组织，直到被人体自身的细胞外基质（ECM）取代。创建理想的可生物降解聚合物支架的两个主要挑战是：（1）脚手架必须具有定义的形状和多孔内部体系结构，适用于直接组织内部，但具有适当的机械和退化特性，并且（2）脚手架必须具有正确的表面特性，以提供有利的细胞条件，以附加分化和放置ECM。为了设计脚手架，这些脚手架会随着时间的推移适当地将其机械负载转移到生长的组织中，需要时间数据来验证重塑构建体的机械可行性。当前的分析方法是破坏性的，需要动物安乐死，并为组织学和直接的机械表征提供了构造。此外，在不同的时间准备并测量不同的样品，但是样品之间的高生长偏差使分析变得困难。理想情况下，组织工程师需要一个系统，该系统可以随着时间的流逝而非侵入性地监测同一标本中的生长。其他成像方法，例如磁共振成像（MRI）和计算机断层扫描（CT），提供了内部支架结构信息，但仅限于提供形态学信息。基于相位敏感斑点跟踪的超声东部成像（UEI）可以表征植入工程组织的机械，结构和功能变化，并以非常高的分辨率和灵敏度为单位。本地UEI提供了从根本上改善生物材料脚手架设计和工程组织生长技术的潜力。该研究计划的长期目标是在组织工程和再生医学领域开发一种新型的非侵入性功能成像方式。当前项目的目的是评估UEI作为无创成像工具，以评估脚手架降解和组织内部的机械，结构和功能特征。具体目的是：（1）建立非侵入性UEI与生物材料支架降解的机械和结构特征之间的体外关系。 （2）在非侵入性UEI与同时组织生长和支架降解的机械，结构和功能特征之间建立体内关系。这些特定目标将使用具有三种不同降解速率的新型聚氨酯软组织支架进行评估。体内可行性也将使用大鼠腹部修复模型证明。如果成功，则将UEI集成到商业超声扫描仪中，也可以迅速转化为临床实践，因为它基于对超声数据的新处理，可以方便，非侵入性地从人类受试者中获得 公共卫生相关性：组织工程是一个新兴的跨学科领域，对于需要器官和组织更换和修复的人来说，充满希望。但是，由于实验室反馈能力的局限性，尤其是动物研究中植入物的非侵入性评估工具，主要是由于实验室反馈能力的局限性，其开发和翻译的一些主要局限性仍未解决。组织工程治疗的临床应用还需要非侵入性监测功能组织再生的能力。所提出的超声弹性成像技术将在工程组织生长成天然组织时对工程组织的机械强度进行定量评估和监测。该技术可以轻松地集成到实时体内动物研究的商业超声扫描仪中，从而大大减少了研究中所需的动物数量，并最终是监测组织工程处理的临床工具。