Engineering MicroEnvironment Core (EMEC)

项目摘要-核心C 新的临床前呼吸道和胃肠上皮模型，特别是那些充分 反映相关的人体3D生理学和疾病病理生理学，是阐明疾病亟需的 机制，并找出治疗途径。工程微环境的总体目标 核心(EMEC)是为仿生合作研究中心(BCRC)的研究人员小组提供 生物材料和流体室平台和其他使能技术改善人类 用于项目1-3和人体仿生科学中提出的研究的胃肠和肺系统 核心(HBSC，核心B)。这些仿生系统被设计成复制上皮细胞的关键方面 三维生理和物理环境。这些平台将利用生物材料和组织工程 我们在最初的NAMSED投资中建立的技术，也将建立在这些技术的基础上 扩展我们的能力以回答有关宿主粘液层、细胞物理作用的问题的技术 肠道和肺部感染的微环境和细胞群落。EMEC的服务组成部分 解剖结构不同的上皮细胞的培养，(2)构建组织工程/生物材料平台以支持 肠道上皮细胞±病原体，(4)氧敏传感器的制作和维护 制作，(6)量化组织和生物流体的力学行为，以制备体外生理模型 忠实的材料性质，(7)液体动力学和氧在培养中传输的计算模型 EMEC的开发组件将增强先前测试的培养系统，以模拟 拟议研究中3D主机环境的复杂性，通过(1)开发对 具有双流动的TransWell槽模型，(2)修改水凝胶以实现免疫和 用于共培养研究的神经细胞，(3)开发一种改进的MPC系统以在 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、工具和服务将节省 时间、精力和成本，加快发现速度，并实现跨项目的结果比较 只要有可能。EMEC将对个别项目的需要进行协商和回应，这些项目 可能会随着研究的进行和整个领域的发展而变化。将开发新的活动以满足 项目调查员的需求。我们的目标是在这些努力中互补和合作，以发展 仿生工程模型，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.