Engineering MicroEnvironment Core (EMEC)

工程微环境核心 (EMEC)

• 批准号: 10462790
• 负责人: KATHRYN JANE GRANDE-ALLEN
• 金额: $ 16.51万
• 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/10462790
• 关键词: 3-Dimensional; 3D Print; Anatomy; Biocompatible Materials; Biological Models; Biomechanics; Biomedical Engineering; Biomimetics; Biophysics; Cardiovascular system; Categories; Cell Adhesion; Cell Culture Techniques; Cells; Coculture Techniques; Communicable Diseases; Computer Models; Connective Tissue; Consultations; Custom; Development; Disease; Engineering; Enteral; Environment; Epithelial; Epithelial Cells; 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; base; 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; pathogen; professor; respiratory; screening; tool

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的临床前模型，尤其是那些适当的上皮 反映相关的人类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 Core（EMEC）是为仿生协作研究中心（BCRC）研究人员提供 生物材料和流体室平台以及其他能够改善人类的技术 在项目1-3和人类仿生科学的研究中提出的研究的胃肠道和肺系统 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物理环境。这些平台将利用生物材料和组织工程 我们在原始命名资金中建立的技术，也将基于这些技术 扩大我们能力的技术，以回答有关宿主粘液层的作用，细胞物理的问题 微环境以及肠道和肺部感染中的细胞群落。 EMEC的服务组成部分 将提供工程工具，包括（1）准备“ Trangwell”系统以应用流程 解剖上上皮细胞的培养物，（2）制造组织工程/生物材料平台以支持 肠道或肺上皮细胞培养物，（3）制造毫米流体灌注室（MPC），以使流过流过 肠上皮细胞±病原体（4）制造和维持氧气的校准库存 基于水凝胶的微粒，（5）3D霉菌的印刷和其他培养系统的其他成分是 制造的，（6）量化组织和生物流体机械行为，以便在体外模型中进行物理上的体外模型 忠实的材料特性，（7）培养中流体动力和氧运输的计算建模 系统，以及（8）通过其他资助U19的培训小组成员和人员转移技术。 EMEC的开发成分将增强先前测试的培养系统，以模仿 3D主机环境在拟议的研究中的复杂性，通过（1）形成修改 具有双流动的Trandwell槽模型，（2）修改水凝胶以实现3D封装的免疫和 神经细胞用于共培养研究，（3）开发一个改良的MPC系统，以在A上种植上皮细胞 仿生水凝胶表面和（4）开发自定义的粘膜模拟物以促进宿主筛查 粘液病原体相互作用。通过中心核心提供这些平台，工具和服务将节省 时间，精力和成本，加速发现率，并能够比较项目的结果 尽可能。 EMEC将对单个项目的需求进行咨询和响应， 随着研究的进行和整体领域的发展，可能会发生变化。将开发新的活动以满足 项目调查人员的需求。我们的目标是完整和协作的，以发展 仿生工程模型研究宿主粘膜表面在肠和呼吸道感染中的作用。