Bioreactor suite to study mechanical loading in skeletal tissues & biomaterials

每天，我们的骨骼和关节都要承受持续的机械载荷，包括压缩、拉伸和/或静水载荷。这些负荷是调节这些组织内细胞功能的重要信号。我们的跨学科协作研究团队包括椎间盘(S)、软骨(贝尔)、滑膜(阿普尔顿)、肌腱和骨生物学(GROL)的专家，以及生物材料(弗林)和细胞表面受体生物学(Ramachandran)的专家。这个团队有着卓有成效的合作记录，反映了我们对研究多样性的共同信念，包括不同职业阶段的个人，来自代表性不足的群体，在传统上由男性主导的学科中女性领导和性别平衡的重要性。总之，由NSERC资助的由该团队领导的研究正在调查机械信号如何在发育、组织动态平衡和组织再生的背景下调节骨骼组织的生物学。我们目前研究中的一个关键差距是能够对3D组织或生物材料中细胞的复杂机械环境进行建模，以便研究潜在的细胞过程和/或使用这些信号来刺激细胞进行组织再生。为了满足这一基本需求，本申请寻求资金支持购买一套生物反应器-这些设备将使我们能够在实验室环境中随着时间的推移向3D组织或生物材料提供精确的机械载荷。这套集成的设备将允许同时加载多个组织(并行或不同加载方案)的实验，这些组织旨在模拟骨骼组织在体内经历的静水压力(MCTR)、单轴压缩(MCTX)或单轴拉伸(MCJ1和MCFX)加载。所要求的系统具有独特的特点，包括在多个独立的井中独立机械加载样品的设计。这一特点允许高通量实验，容纳不同大小/形状的组织。独立的Well系统允许我们在加载过程中调节关键的细胞效应器(例如，使用药物或小分子)，或者测量组织在加载过程中分泌的可能向相邻细胞/组织发出信号的因子。最后，这些系统可以在整个实验过程中测量组织的机械性能，使我们能够从功能上实时测量载荷对组织重塑或适应的影响，这是目前无法实现的。所要求的设备将创建一个独特的资源，以支持西部地区的HQP培训。在我们的基础生物学研究中，对组织力学的关注支持合作，并为学员提供发展和领导跨学科研究的机会。此外，我们与CellScale在设备设计和应用方面的合作为学员提供了对行业和产品开发的重要见解。

Every day, our bones and joints are subjected to continual mechanical load in the form of compression, tension and/or hydrostatic loading. These loads are important signals that regulate the function of cells within these tissues. Our collaborative transdisciplinary team of researchers includes experts in intervertebral disc (Séguin), cartilage (Beier), synovium (Appleton), tendon and bone biology (Grol), partnered with experts in biomaterials (Flynn) and cell surface receptor biology (Ramachandran). This team has an established track record of productive collaboration and reflects our shared belief in the importance of diversity in research, including individuals at various career stages, from under-represented groups, with a female lead and gender balance in traditionally male-dominated disciplines. Together, NSERC-funded research being led by this team is investigating how mechanical signals regulate the biology of skeletal tissues in the context of development, tissue homeostasis, and tissue regeneration. A critical gap in our current research is the ability to model the complex mechanical environment of cells within 3D tissues or biomaterials in order to study the underlying cellular processes and/or use these signals to stimulate cells for tissue regeneration. To address this essential need, the current application seeks funding to support the purchase of a suite of bioreactors - equipment that will enable us to deliver precise mechanical loads to 3D tissues or biomaterials over time in the laboratory setting. The integrated suite of equipment will allow for experiments that simultaneously load multiple tissues (either in parallel or different loading regimens) designed to simulate the hydrostatic pressure (MCTR), uniaxial compression (MCTX), or uniaxial tension (MCJ1 and MCFX) loading that skeletal tissues experience in the body. The requested systems have unique features, including a design for independent mechanical loading of specimens within multiple, separate wells. This feature allows high-throughput experiments, accommodating tissues of different sizes/shapes. The separate well systems allow us to modulate key cellular effectors during loading (e.g. using drugs or small molecules) or measure the factors secreted by tissues during load that may signal to adjacent cells/tissues. Lastly, these systems can measure a tissue's mechanical properties throughout the experiment, enabling us to functionally measure, in real time, the effects of loading on tissue remodeling or adaptation that is currently not possible. The requested equipment will create a unique resource to support HQP training at Western. The focus on tissue mechanics in our basic biology studies supports collaboration and gives trainees the opportunity to develop and lead transdisciplinary research. Furthermore, our collaboration with CellScale in equipment design and application allows trainees important insights into industry and product development.