Engineering MicroEnvironment Core (EMEC)

工程微环境核心 (EMEC)

• 批准号: 10642942
• 负责人: KATHRYN JANE GRANDE-ALLEN
• 金额: $ 20.19万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642942
• 关键词: 3-Dimensional; 3D Print; Acceleration; Anatomy; Biocompatible Materials; Biological Models; Biomechanics; Biomedical Engineering; Biomimetics; Biophysics; Calibration; Cardiovascular system; Categories; Cell Adhesion; Cell Culture Techniques; Cells; Coculture Techniques; Communicable Diseases; Computer Models; Connective Tissue; Development; Disease; Encapsulated; Engineering; Enteral; Environment; Epithelial Cells; Epithelium; Extracellular Matrix; Functional disorder; Funding; Goals; Human; Human Resources; Hydrogels; Immune; Individual; Infection; Infectious Diseases Research; Intestines; Knowledge; Leadership; Liquid substance; Lung; Lung infections; Mechanical Stimulation; Modeling; Modification; Molds; Mucous Membrane; Mucous body substance; Neurons; Oxygen; Pathogenesis; Perfusion; Physical environment; Physiological; Physiology; Pre-Clinical Model; Production; Property; Public Health; Research; Research Personnel; Respiratory Disease; Respiratory Tract Infections; Rice; Role; Services; Surface; System; Technology; Technology Transfer; Testing; Time; Tissue Engineering; Tissues; Training; United States National Institutes of Health; Universities; Work; airway epithelium; cell community; cell transformation; cost; design; enteric infection; experience; gastrointestinal; gastrointestinal epithelium; gastrointestinal system; human disease; human tissue; improved; in vitro Model; intestinal epithelium; mechanical behavior; mechanical load; member; novel; oxygen transport; pandemic disease; particle; pathogen; professor; respiratory; screening; tool; transmission process

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.

项目摘要 – 核心 C 气道和胃肠道上皮的新临床前模型，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，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）旨在为仿生合作研究中心（BCRC）研究人员提供 生物材料和流体室平台以及其他使能技术能够改善人类 胃肠道和肺系统用于项目 1-3 和人类仿生科学中提出的研究 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。 这些平台将利用生物材料和组织工程的 3D 生理和物理环境。 我们在最初的 NAMSED 资助期间建立的技术，也将建立在这些技术的基础上 扩展我们回答有关宿主粘液层的作用、细胞物理学等问题的能力的技术 肠道和肺部感染的微环境和细胞群落是 EMEC 的服务组成部分。 将提供工程工具，包括（1）准备“TransWell Trough”系统，将流量应用于合作 解剖学上不同的上皮细胞培养物，（2）制造组织工程/生物材料平台来支持 肠或肺上皮细胞培养物，(3) 制造用于流过的微流体灌注室 (mPC) 肠上皮细胞±病原体，（4）制造和维护校准的氧传感储备 基于水凝胶的微粒，(5) 3D 打印模具和培养系统的其他组件 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模型 (8) 通过培训小组成员和其他受资助 U19 的人员转让技术。 EMEC 的开发部分将增强先前测试的培养系统以模仿 拟议研究中 3D 主机环境的复杂性，通过 (1) 开发对 具有双流的 TransWell 槽模型，(2) 修改水凝胶以实现免疫和免疫细胞的 3D 封装 用于共培养研究的神经细胞，(3) 开发改良的 mPC 系统，使上皮细胞在 仿生水凝胶表面，以及（4）开发定制的粘膜模拟物以促进宿主筛选 通过中央核心提供这些平台、工具和服务将节省粘液-病原体相互作用。 时间、精力和成本，加快发现速度，并实现跨项目结果的比较 只要有可能，EMEC 就会对各个项目的需求进行协商和响应。 随着研究的进展和整个领域的发展，可能会发生变化以满足新的活动。 我们的目标是在这些努力中实现互补和协作，以开发项目研究人员的需求。 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。