Mechanical Testers to Support the Development of In Vitro 3D Tissue Models

健康的组织有胶原蛋白和弹性纤维组成的网络。该网络为周围细胞提供结构和生化支持，这对组织和器官的正常运作至关重要。健康的组织有一个结构良好的网络，含有适量的胶原蛋白、弹性纤维和其他成分。当组织受损时，会发生一个称为“疤痕形成”的过程，这是一个有益的损伤愈合过程。然而，过度的伤口愈合反应会导致胶原蛋白的积累，从而阻碍器官的正常功能——这种情况被称为“纤维化”。纤维化可发生在许多组织中，包括肺、肝、心和脑，是几种疾病的标志，包括某些类型的癌症、动脉粥样硬化和哮喘。在这个提案中，我们需要两个系统来支持我们已经建立的组织工程基础设施，以提供我们新开发的体外组织模型的机械测试能力。我们的模型专注于更好地理解几种情况下（如哮喘、癌症、慢性伤口）纤维化的基本机制。由于组织微观结构在纤维化过程中发生显著改变，因此与自然组织中的生物力学特性相匹配对于开发先进的生理相关人工组织模型至关重要。所要求的系统将允许：i)生物工程构建体的机械刺激以模拟体内发现的条件；ii)具有高力分辨率（即nN量级）的体外模型的力学性能评估。即使在最简单的组织中，机械完整性和力的传递对正常功能至关重要，组织微环境中产生的物理力影响细胞的生长、迁移和分化。失调会减弱组织的机械强度。越来越多的证据表明，破坏张力稳态可以激活机械敏感信号通路，因此，在开发3D组织模型时必须考虑组织力学特性。所要求的系统不仅将直接支持申请人的研究项目，而且还将支持组织工程和应用材料中心（TEAM）的集体努力-一个旨在研究组织工程的多个跨学科方面以造福加拿大医疗保健系统的区域研究计划。由于这些仪器的高度专业化，并使它们在学术环境中可用，将支持HQP在生物材料和人工组织开发方面的培训。所有这些都在一个独特的，包容的，高度跨学科的科学网络中。随着这一网络的快速扩展，通过建立新的合作关系，我们的战略定位是寻找重要科学问题的答案，同时加强加拿大在新兴的组织工程领域的创新和全球影响力。

Healthy tissues have a network of collagen and elastic fibers. This network provides structural and biochemical support to surrounding cells, which is important for tissues and organs to function properly. Healthy tissues have a well-structured network with the right amount of collagen, elastic fibers, and other components. When a tissue is damaged, a process called "scar formation" occurs, which is a beneficial process of injury healing. However, an exaggerated wound healing response results in the build-up of collagen that impedes normal organ function - a condition called "fibrosis". Fibrosis can occur in many tissues including the lungs, liver, heart, and brain, and is a hallmark of several diseases including certain types of cancer, atherosclerosis, and asthma. In this proposal we are requesting two systems to support our already-established tissue engineering infrastructure, to provide the capability of performing mechanical testing of our newly developed in vitro tissue models. Our models are focused on determining a better understanding of the basic mechanisms underlying fibrosis in several contexts (e.g., asthma, cancer, chronic wounds). Since tissue microstructure is significantly altered during fibrosis, matching the biomechanical properties found in naturally occurring tissues is crucial for developing advanced physiologically-relevant artificial tissue models. The requested systems will allow for: i) the mechanical stimulation of bioengineered constructs to mimic conditions found in vivo; ii) the assessment of mechanical properties of in vitro models with high force resolution (i.e., nN magnitudes). Mechanical integrity and force transmission, in even the simplest tissues, are critical to proper functioning, and physical forces generated in the tissue microenvironment affect cell growth, migration, and differentiation. Dysregulation can attenuate tissue mechanical strength. Growing evidence suggests that disrupting tensional homeostasis can activate mechanosensitive-signalling pathways, and therefore, tissue mechanical properties must be considered in the development of 3D tissue models. The requested systems will directly support not only the applicant's research program, but also collective efforts of the Tissue Engineering and Applied Materials (TEAM) Hub - a regional research initiative aiming to study multiple interdisciplinary aspects of tissue engineering to the benefit of Canada's healthcare system. Due to the high specialization of such instruments and making them available in an academic environment will support HQP training in biomaterials and artificial tissues development. All within a unique, inclusive, and highly interdisciplinary scientific network. With the quick expansion of this network by establishing new collaborations, we are strategically positioned to find answers to important scientific questions while enhancing Canadian innovation and global presence in the burgeoning field of tissue engineering.