Ultrasound Technologies for Tissue Engineering

描述（由申请人提供）： 工程组织的成功构建需要重新创建一个生物活性的细胞外环境，在其中开发产品。超声治疗目前在临床上用于促进骨愈合，并已被证明可以增强软组织修复。已知超声的一些生物效应是由与声波传播相关联的机械力引起的。体外研究表明，机械应力积极影响细胞外基质（ECM）的组织和细胞行为。因此，我们假设声驱动的机械力可用于控制ECM沉积并促进细胞和组织功能。在这个建议中，我们联合收割机结合我们的ECM生物学和生物医学超声的知识，开发基于超声的使能技术，用于功能性3D ECM和组织类似物的制造和监测。为了实现这一目标，我们制定了四个具体目标。在目标1中，我们将使用超声场来制造ECM FN和胶原类似物，并优化超声暴露条件，以增强ECM介导的成纤维细胞和上皮细胞生长。在目标2中，我们将开发使用声学驱动的机械力来促进成纤维细胞迁移到3D、基于胶原蛋白的组织构造中。在目标3中，我们将使用声场来刺激ECM组织，以工程化基于胶原蛋白的组织构建物的生物学和材料特性。在目标4中，我们将应用并扩展我们在超声组织定征技术方面的经验，以实时非破坏性地量化工程组织的机械和生物学特性。我们设想使用超声技术为组织制造和监测提供突破性技术的巨大潜力。此外，超声波作为聚焦波束通过组织传播的能力有可能提供一种革命性的方法来局部调节和监测体内深处的组织再生。组织工程是一种潜在的革命性方法，用于替换或再生患病或受损的器官和组织。目前缺乏可用的组织类似物反映了无法创建具有生物活性和足够机械强度的3D支架。我们将开发基于超声的使能技术，该技术具有双重能力：（i）创建用于组织工程的生物活性3-D组织结构，以及（ii）非侵入性地监测这些结构的生物和机械特性。 (End摘要）

DESCRIPTION (provided by applicant): The successful construction of engineered tissues requires the re-creation of a biologically active extracellular environment in which to develop the product. Ultrasound therapy is currently used clinically to promote bone healing and has been shown to enhance soft tissue repair. Some biological effects of ultrasound are known to result from the mechanical forces associated with acoustic wave propagation. In vitro studies demonstrate that mechanical stresses positively affect both extracellular matrix (ECM) organization and cell behavior. Thus, we hypothesize that acoustically-driven mechanical forces can be used to control ECM deposition and promote cell and tissue function. In this proposal, we combine our knowledge of ECM biology and biomedical ultrasound to develop ultrasound-based enabling technologies for the fabrication and monitoring of functional 3D ECM and tissue analogs. To accomplish this goal, we have developed four specific aims. In Aim 1, we will use ultrasound fields to fabricate ECM FN and collagen analogs, and optimize ultrasound exposure conditions that enhance ECM-mediated fibroblast and epithelial cell growth. In Aim 2, we will develop the use of acoustically-driven mechanical forces to promote fibroblast migration into 3D, collagen- based tissue constructs. In Aim 3, we will use acoustic fields to stimulate ECM organization in order to engineer the biological and material properties of collagen-based tissue constructs. In Aim 4, we will apply and extend our experience in ultrasound tissue characterization technologies to non-destructively quantify mechanical and biological properties of engineered tissues in real-time. We envision immense potential for the use of ultrasound technologies to provide break-through technologies for tissue fabrication and monitoring. Furthermore, the ability of ultrasound to propagate through tissue as a focused beam has the potential to provide a revolutionary approach to locally regulate and monitor tissue regeneration deep within the body. Tissue engineering is a potentially revolutionary approach for replacing or regenerating diseased or destroyed organs and tissues. The current lack of available tissue analogs reflects an inability to create 3-D scaffolds that have both biological activity and adequate mechanical strength. We will develop ultrasound- based enabling technologies with the dual capacity to (i) create biologically-active, 3-D tissue constructs for tissue engineering and (ii) non-invasively monitor the biological and mechanical properties of these constructs. (End of Abstract)