Microscale Mechanobiology for Musculoskeletal Tissue Engineering using Advanced Ultrasound Techniques

使用先进超声技术进行肌肉骨骼组织工程的微观力学生物学

基本信息

批准号：
9974508
负责人：
CHERI X DENG
金额：
$ 36.19万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9974508
关键词：
3-Dimensional Acoustics Anisotropy Bone Regeneration Calvaria Cell physiology Cells Clinical Cues Data Defect Development Engineering Environment Extracellular Matrix Focused Ultrasound Frequencies Goals Histology Hydrogels Image In Vitro Joints Knowledge Lead Length Measures Mechanical Stimulation Mechanics Mesenchymal Differentiation Mesenchymal Stem Cells Methods Minerals Modality Modeling Monitor Musculoskeletal Osteogenesis Periodicity Phenotype Play Property Pulse Pressure Radiation Regenerative Medicine Relaxation Resolution Role Sampling Spinal Fusion Stress Stress Tests System Techniques Testing Therapeutic Therapeutic Intervention Three-dimensional analysis Time Tissue Engineering Tissues Ultrasonography Work base bone cell dimension design elastography healing improved improved outcome in vivo in vivo regeneration innovation insight mechanical force mechanical properties microCT osteogenic physical property pressure radio frequency response spatiotemporal stem cells tissue regeneration tool two-dimensional viscoelasticity

项目摘要

Project Summary Mechanical forces are a key component of the cellular microenvironment, and are well established to have potent effects on cells and tissues. The passive mechanical properties of two-dimensional cell substrates and three-dimensional extracellular matrices have been shown to influence progenitor cell phenotype and can be used to direct cell function. In addition, active stimulation of cells and tissues using externally applied forces has been applied at both the cell and tissue level to induce a variety of responses. Mechanobiology is particularly relevant to musculoskeletal tissues, but there is a gap in our understanding of the physical properties of the tissue environment on length scales that cells sense. This project builds on preliminary work by the project team in applying advanced ultrasound techniques to studying the microscale physical properties of engineered musculoskeletal tissues composed of cell-seeded mineralizing hydrogels. It integrates spectral ultrasound imaging (SUSI), dual-mode ultrasound elastography (DUE), and ultrasound-induced compressive stimulation. SUSI is a technique that uses the backscattered radiofrequency spectrum to derive information about the composition of a sample. DUE applies acoustic radiation force to deform hydrogels and measure their mechanical properties. Focused ultrasound-induced compression also applies acoustic pressure to mechanically stimulate tissues. A key feature of ultrasound techniques is that they are noninvasive and therefore can be used to study developing tissues over time. In addition, imaging and deformation can be applied at sub-millimeter resolution. This project will combine these advanced ultrasound techniques to create a system that can comprehensively characterize and stimulate engineered musculoskeletal tissues at the microscale. The target application is to potentiate bone formation using mesenchymal stem cells (MSC) embedded in a 3D hydrogel matrix. The Specific Aims are 1) to integrate spectral ultrasound imaging (SUSI) and dual-mode ultrasound elastography (DUE) to compositionally and mechanically characterize mineralizing tissues, 2) to probe the effects of passive matrix mechanical properties on MSC phenotype using SUSI-DUE, 3) to actively stimulate osteogenic differentiation of MSC in hydrogel matrices using ultrasound-induced cyclic compression, and 4) to apply SUSI-DUE to catalyze and monitor bone regeneration in vivo. This project will investigate musculoskeletal mechanobiology using an innovative new tool that could have important impact on regenerative medicine. The long term goal is a therapeutic intervention to potentiate bone formation in indications where accelerated healing would lead to improved outcomes, such as treatment of non-unions and recalcitrant spinal fusions.

项目概要机械力是细胞微环境的关键组成部分，并且已被广泛证实对细胞和组织的有效作用。二维电池基底的被动机械性能和三维细胞外基质已被证明可以影响祖细胞表型，并且可以用于指导细胞功能。此外，利用外力主动刺激细胞和组织已应用于细胞和组织水平以诱导多种反应。力学生物学是与肌肉骨骼组织特别相关，但我们对物理的理解存在差距组织环境在细胞感知的长度尺度上的特性。该项目建立在前期工作的基础上项目团队应用先进的超声波技术来研究微观物理特性由细胞接种的矿化水凝胶组成的工程肌肉骨骼组织。它集成了光谱超声成像 (SUSI)、双模式超声弹性成像 (DUE) 和超声诱导压缩刺激。 SUSI 是一种利用反向散射射频频谱来获取信息的技术关于样品的组成。 DUE 应用声辐射力使水凝胶变形并测量他们的机械性能。聚焦超声引起的压缩也将声压施加到机械刺激组织。超声技术的一个关键特点是它们是非侵入性的因此可用于研究随着时间的推移发育的组织。此外，成像和变形可以以亚毫米分辨率应用。该项目将结合这些先进的超声技术来创建一个可以全面表征和刺激工程肌肉骨骼组织的系统微量。目标应用是利用间充质干细胞 (MSC) 增强骨形成嵌入 3D 水凝胶基质中。具体目标是 1) 集成频谱超声成像 (SUSI) 和双模式超声弹性成像 (DUE) 来表征矿化的成分和机械特征组织，2) 使用 SUSI-DUE 探讨被动基质机械特性对 MSC 表型的影响， 3）利用超声诱导的循环积极刺激水凝胶基质中MSC的成骨分化压缩，4) 应用 SUSI-DUE 催化和监测体内骨再生。该项目将使用可能对肌肉骨骼力学生物学产生重要影响的创新工具进行研究再生医学。长期目标是通过治疗干预来增强骨形成加速愈合将导致改善结果的迹象，例如不愈合和不愈合的治疗顽固性脊柱融合。