Engineering MicroEnvironment Core (EMEC)

项目概要-核心C 新的气道和胃肠道上皮的临床前模型，特别是那些充分 反映相关的人类3D生理学和疾病病理生理学，是迫切需要阐明疾病 机制，并确定治疗途径。工程微环境的总体目标 核心（EMEC）是为仿生合作研究中心（BCRC）的研究人员提供 生物材料和流体腔室平台以及另外的使能技术来改善人类的健康状况。 胃肠道和肺系统的研究项目1-3和人类仿生科学 核心（HBSC，核心B）。这些仿生系统旨在复制上皮细胞的关键方面， 3D生理和物理环境。这些平台将利用生物材料和组织工程 我们在最初的NAMSED资助期间建立的技术，也将在这些技术的基础上发展 技术，以扩大我们的能力，以回答有关主机粘液层的作用，细胞物理的问题， 微环境和肠道和肺部感染中的细胞群落。EMEC的服务组件 将提供工程工具，包括（1）准备“TransWell槽”系统，以应用流量， 解剖学上不同的上皮细胞的培养物，（2）制造组织工程/生物材料平台以支持 肠或肺上皮细胞培养物，（3）制造用于流过的毫流体灌注室（mPC）， 肠上皮细胞±病原体，（4）制造和维持校准的氧传感储备 水凝胶基微粒，（5）模具和培养系统的其他组件的3D打印， 制造，（6）量化组织和生物流体机械行为以制备具有生理学的体外模型 忠实的材料特性，（7）培养物中流体动力学和氧传输的计算建模 系统，以及（8）通过培训小组成员和其他受资助的U19人员转让技术。 EMEC的开发组件将增强先前测试的培养系统，以模拟 3D主机环境的复杂性，通过（1）开发一个修改的 具有双流动的TransWell槽模型，（2）修改水凝胶以实现免疫和 神经细胞共培养研究，（3）开发一种改良的mPC系统， 仿生水凝胶表面，以及（4）开发定制的粘膜模拟物以便于筛选宿主 粘液-病原体相互作用通过中央核心提供这些平台、工具和服务， 时间、精力和成本，加快发现速度，并支持跨项目比较结果 只要有可能EMEC将对各个项目的需求进行咨询和响应， 可能会随着研究的进行和整个领域的发展而改变。将开展新的活动， 项目调查人员的需求。我们的目标是在这些努力中相互补充和合作， 仿生工程模型，以研究宿主粘膜表面在肠道和呼吸道感染中的作用。

PROJECT SUMMARY – Core C New pre-clinical models of both the airway and gastrointestinal epithelium, especially those that adequately reflect relevant human 3D physiology and disease pathophysiology, are desperately needed to elucidate disease mechanisms and identify avenues for treatment. The overall objective of the Engineering MicroEnvironment Core (EMEC) is to provide the group of Biomimetic Collaborative Research Center (BCRC) investigators with biomaterial and fluidic chamber platforms and additional enabling technologies to improve human gastrointestinal and lung systems for the studies proposed in Projects 1-3 and the Human Biomimetic Scientific Core (HBSC, Core B). These biomimetic systems are designed to replicate key aspects of the epithelial cells’ 3D physiological and physical environment. These platforms will utilize the biomaterial and tissue engineering technologies that we established during our original NAMSED funding, and will also build upon these technologies to expand our capabilities to answer questions about the role of the host mucus layer, cell physical microenvironment, and cell communities in intestinal and lung infections. The service component of the EMEC will be to provide engineering tools, including (1) preparing “TransWell Trough” systems to apply flow to co- cultures of anatomically-distinct epithelial cells, (2) fabricating tissue engineering/biomaterial platforms to support intestinal or lung epithelial cell cultures, (3) fabricating millifluidic perfusion chambers (mPC) for flow across intestinal epithelial cells ± pathogens, (4) fabricating and maintaining calibrated stocks of oxygen-sensing hydrogel-based microparticles, (5) 3D printing of molds and other components of the culture systems being fabricated, (6) quantifying tissue and biofluid mechanical behavior to prepare in vitro models with physiologically faithful material properties, (7) computational modeling of fluid dynamics and oxygen transport in culture systems, and (8) transferring technology through training group members and personnel at other funded U19s. The development component of EMEC will enhance the previously tested culture systems to mimic the complexity of the 3D host environment in the proposed studies, through (1) developing a modification of the TransWell Trough model with dual flow, (2) modifying the hydrogels to enable 3D encapsulation of immune and neural cells for co-culture studies, (3) developing a modified mPC system to grow the epithelial cells atop a biomimetic hydrogel surface, and (4) developing customized mucosal mimics to facilitate screening of host mucus-pathogen interactions. Providing these platforms, tools, and services through a central core will save time, effort, and costs, accelerate the rate of discovery, and enable comparison of results across Projects whenever possible. The EMEC will be consultative and responsive to needs of the individual Projects, which may change as the research proceeds and as the overall field evolves. New activities will be developed to meet the needs of the Project investigators. Our goal is complementary and collaborative in these efforts to develop biomimetic engineering models to study the role of the host mucosal surface in enteric and respiratory infections.