Biomimetic Assembly of Microphysiological Lacunocanalicular Network

非技术：史蒂文斯理工学院材料研究部生物材料项目的这一奖项旨在开发可用于代替动物试验进行药物评估的人类组织样材料。骨细胞调节成骨细胞以形成新骨是开发新药的主要目标，用于治疗1000万骨质疏松症患者和骨转移癌症患者，美国每年有35万人死亡。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，因为已知后者不能很好地预测人类的药物反应。因此，这项研究将提供一个重要的新的见解，在解决制药行业的需要，以减少昂贵的药物失败的数量，发生在临床试验。关于更广泛的影响，该项目将带来发现，合作和创业精神的兴奋：1）通过跨学科活动的研究生; 2）通过夏季研究经验的本科生;和3）通过美国化学学会的经济困难高中生夏季研究实习计划的高中生。学生将面临制定商业计划的挑战，这些计划可以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：有了这一奖项，研究人员将在体外重建人类皮质骨的三维（3D）腔隙性神经网络结构。为了模拟网络的多尺度3D几何特征，仿生方法将用于在微流体灌注培养室内分层组装微珠和纳米颗粒与从人骨中收获的原代骨细胞。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;和（2）第一次离体研究生物材料对骨细胞细胞反应的影响。本项目的具体目标是：（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产生细胞外基质及其骨陷窝小管间隙重塑的影响;和（2）再现重建的骨细胞网络在将相邻的成骨细胞并入细胞网络中并调节成骨细胞向骨细胞的时空转变中的生理作用，作为在稳态骨重建期间形成新骨组织的机制。

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.