Biomimetic Assembly of Microphysiological Lacunocanalicular Network

微生理腔隙小管网络的仿生组装

• 批准号: 1409779
• 负责人: Woo Lee
• 金额: $ 39万
• 依托单位: Stevens Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1409779&HistoricalAwards=false
• 关键词: Biomimetic; Assembly; Microphysiological; Lacunocanalicular; Network

Non-Technical: This award by the Biomaterials Program in the Division of Materials Research to Stevens Institute of Technology is to develop human tissue-like materials that could be used in place of animal testing for drug evaluation. The regulation of osteoblasts by osteocytes for new bone formation is a major target for development of new drugs for treating 10 million osteoporosis patients, and cancer patients with bone metastases which result in 350,000 deaths every year in the U.S. For these diseases, this project will provide a more clinically relevant method of evaluating drugs than animal testing, as the latter is known to poorly predict drug response in humans. This study will, therefore, offer an important new insight in addressing pharmaceutical industry's need to lower the number of costly drug failures that occur during clinical trials. With regard to broader impacts, this project will bring the excitement of discovery, collaboration, and entrepreneurship to: 1) graduate students through interdisciplinary activities; 2) undergraduate students via summer research experiences; and 3) high school students through the American Chemical Society's Summer Research Internship Program for Economically Disadvantaged High School Students. Students will be challenged to develop business plans that can translate discoveries to entrepreneurial opportunities at levels appropriate for their educational stages. This innovation theme is important in our geographical area where biomedical research plays a key role in propelling the regional, national, and global economies.Technical: With this award, the investigators will reconstruct in vitro the 3-dimensional (3D) lacunocanalicular network structure of cortical human bones. In order to mimic the network's multi-scale 3D geometrical features, a biomimetic approach will be used to hierarchically assemble microbeads and nanoparticles with primary osteocyte cells harvested from human bones within a microfluidic perfusion culture chamber. The biomimetic approach will enable: (1) long-term culture of primary human osteocytes which has not been possible to date; and (2) ex vivo investigation of biomaterial effects on the cellular response of osteocytes for the first time. The specific objectives of the project are to: (1) investigate the effects of biphasic calcium phosphate and hydroxyapatite nanoparticles on extracellular matrix production by human primary osteocytes and remodeling of their lacunocanalicular space; and (2) reproduce the physiological role of the reconstructed osteocyte network in incorporating neighboring osteoblasts into the cellular network and regulating the spatiotemporal transition of the osteoblasts to osteocytes, as mechanisms by which new bone tissue is formed during homeostatic bone remodeling.

非技术领域：史蒂文斯理工学院材料研究部生物材料项目授予该奖项的目的是开发类似人体组织的材料，用于代替动物试验进行药物评估。骨细胞调节成骨细胞形成新骨是开发新药的主要目标，用于治疗美国每年导致35万例死亡的1000万骨质疏松症患者和骨转移癌患者。对于这些疾病，该项目将提供比动物试验更具有临床相关性的药物评估方法，因为后者很难预测人类的药物反应。因此，这项研究将为解决制药行业在降低临床试验期间发生的昂贵药物失败数量的需求提供重要的新见解。就更广泛的影响而言，该项目将为研究生带来发现、合作和创业的兴奋：1)通过跨学科活动；2)本科生通过暑期调研体验；3)通过美国化学学会为经济困难高中生提供的暑期研究实习计划的高中生。学生将面临的挑战是制定商业计划，将发现转化为适合其教育阶段的创业机会。这一创新主题在我们的地理区域非常重要，因为生物医学研究在推动区域、国家和全球经济方面发挥着关键作用。技术：有了这个奖项，研究人员将在体外重建人类皮质骨的三维（3D）腔管网络结构。为了模拟网络的多尺度三维几何特征，将使用仿生方法在微流控灌注培养室中将微珠和纳米颗粒与从人骨中收获的原代骨细胞分层组装。仿生方法将使：(1)长期培养原代人骨细胞，这是迄今为止不可能的；(2)首次在体外研究了生物材料对骨细胞细胞反应的影响。该项目的具体目标是：(1)研究双相磷酸钙和羟基磷灰石纳米颗粒对人原代骨细胞细胞外基质产生和骨腔管腔重塑的影响；(2)再现重建骨细胞网络的生理作用，将邻近的成骨细胞纳入细胞网络，并调节成骨细胞向骨细胞的时空转变，作为在稳态骨重塑过程中形成新骨组织的机制。