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

点击翻译按钮获取中文摘要

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.