Ultrasound Technologies for Tissue Engineering

描述(由申请人提供)： 成功构建工程化组织需要重新创造一个具有生物活性的细胞外环境，在其中开发产品。超声波治疗目前在临床上用于促进骨愈合，并已被证明可以促进软组织修复。已知超声波的一些生物效应是由与声波传播相关的机械力引起的。体外研究表明，机械应力对细胞外基质(ECM)的组织和细胞行为都有积极的影响。因此，我们假设声学驱动的机械力可以用来控制细胞外基质沉积，促进细胞和组织功能。在这项提案中，我们将我们对ECM生物学和生物医学超声的知识结合起来，开发基于超声波的使能技术，用于制造和监测功能性3D ECM和组织类似物。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备细胞外基质FN和胶原类似物，并优化超声暴露条件，以促进细胞外基质介导的成纤维细胞和上皮细胞的生长。在目标2中，我们将开发利用声学驱动的机械力来促进成纤维细胞向3D胶原基组织结构的迁移。在目标3中，我们将使用声场来刺激细胞外基质组织，以设计基于胶原的组织结构的生物和材料特性。在目标4中，我们将应用和扩展我们在超声组织鉴定技术方面的经验，以非破坏性地实时量化工程组织的机械和生物特性。我们展望了利用超声波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在组织中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身体深处的组织再生。组织工程是一种潜在的革命性方法，可以替代或再生患病或被破坏的器官和组织。目前缺乏可用的组织类似物，反映出无法创造既具有生物活性又具有足够机械强度的3D支架。我们将开发基于超声波的使能技术，具有(I)为组织工程创造具有生物活性的3-D组织结构和(Ii)非侵入性地监测这些结构的生物和机械特性的双重能力。(摘要结束)

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)