Biomimetic dynamic mechanobiology: developing control strategies for self-organizing microengineered tissues

仿生动态力学生物学：开发自组织微工程组织的控制策略

• 批准号: RGPIN-2022-05165
• 负责人: Moraes, Christopher
• 金额: $ 4.01万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747171
• 关键词: Biomimetic; dynamic; mechanobiology; developing; control

Nature of the work: The process by which we grow and differentiate from homogenous embryos into precisely-sculpted, functional tissues and organs is a manufacturing marvel that is far more precise, robust, and adaptive than current tissue engineering process control strategies. Mechanical forces are process variables that must play a central role in tissue formation during development, and in tissue disruption during disease; but the tools to measure, recreate, and manipulate these potent stimuli have lagged far behind the explosive growth of reductionist molecular biology techniques. The long-term goals of this research program are to leverage microfabrication, materials design, and stem cell tissue engineering to (1) understand the co-evolution of mechanics and biology as tissues develop and decay; and (2) exploit these insights to engineer biological process systems of value to society. Anticipated outcomes. Over the next five years, we will explore mechanical plasticity as a critical regulator of cell fate and function, and develop tools to measure and manipulate these parameters in native and engineered cultures. We anticipate developing fundamental strategies to understand the mechanical relationship between cells and their environment, with initial applications in organoid differentiation and control. Though broadly applicable to several problems in microscale tissue engineering for human health, we will then apply this paradigm in a focused effort to develop microengineered strategies to reduce the costs of sustainable materials development. Specifically, we will investigate the plastic-to-elastic transition driven by a colonizing fungal network in granular substrates, which has been proposed as a sustainable alternative material for many industries, but remains economically challenging to adopt broadly. This design cycle should hence provide creative and fundamentally-grounded approaches to biological engineering challenges, and we specifically envision the fundamental knowledge and experience gained through this interdisciplinary approach to impact the fundamental research, biomanufacturing, and agricultural industries. Furthermore, this fundamental knowledge will lay the preliminary groundwork to address critical healthcare challenges in drug screening, regenerative medicine, and diagnostics. Benefits to Canada. In addition to the scientific research outcomes described and the potential innovative applications to industry, this proposed work will train 3 doctoral, 3 masters, and 9 undergraduate researchers at the highly interdisciplinary interface between bioprocessing, mechanics, tissue engineering, and sustainable development. Given the pressing need for creative and sustainable approaches to manufacturing, the proposed training environment and program will position trainees ahead of the curve to invent, develop, and deliver creative strategies to effect positive change in a future-focused society.

工作性质：我们从同质胚胎生长和分化为精确造型的功能性组织和器官的过程是一个制造奇迹，比目前的组织工程过程控制策略更精确，更强大，更适应。机械力是过程变量，在发育过程中的组织形成和疾病过程中的组织破坏中必须发挥核心作用;但是测量、重建和操纵这些有效刺激的工具远远落后于还原分子生物学技术的爆炸性增长。该研究计划的长期目标是利用微制造，材料设计和干细胞组织工程来（1）了解组织发育和衰变时力学和生物学的共同进化;以及（2）利用这些见解来设计对社会有价值的生物过程系统。 预期成果。在接下来的五年里，我们将探索机械可塑性作为细胞命运和功能的关键调节器，并开发工具来测量和操纵这些参数在本地和工程文化。我们期望开发基本策略来理解细胞与其环境之间的机械关系，并初步应用于类器官分化和控制。虽然广泛适用于人类健康的微尺度组织工程中的几个问题，我们将应用这种模式，集中精力开发微工程的策略，以降低可持续材料开发的成本。具体来说，我们将研究由颗粒状基质中的定殖真菌网络驱动的塑性到弹性的转变，该基质已被提议作为许多行业的可持续替代材料，但广泛采用仍然具有经济挑战性。因此，这个设计周期应该为生物工程挑战提供创造性和基础性的方法，我们特别设想通过这种跨学科方法获得的基础知识和经验，以影响基础研究，生物制造和农业产业。此外，这些基础知识将奠定初步基础，以解决药物筛选，再生医学和诊断方面的关键医疗挑战。对加拿大有利。除了所描述的科学研究成果和潜在的工业创新应用外，这项拟议的工作还将在生物加工，力学，组织工程和可持续发展之间的高度跨学科界面上培养3名博士，3名硕士和9名本科生研究人员。鉴于迫切需要创造性和可持续的制造方法，拟议的培训环境和计划将使受训者处于领先地位，以发明，开发和提供创造性的战略，从而在以未来为重点的社会中实现积极的变革。