CAREER: Bridging the in vitro - in vivo gap through generation of an enhanced microenvironment model for biologically accurate nanomaterial evaluation

CBET - 1650960 PI：Kristen K.舒适纳米材料（NM）具有巨大的潜力，可以通过日常消费品到生物医学治疗的应用来改善生活质量。纳米利用率的激增导致了纳米浪费的严重程度和人类接触率的增加，从而产生了确保基于纳米的应用程序安全的需求。由于NM行为取决于局部环境因素，这对标准的基于细胞的评估产生了挑战，以产生可靠的数据，因为它们缺乏生理准确性。这项工作致力于克服这些限制，通过将标准的细胞模型转化为一个更能代表人类系统的模型，从而开发出一个更能代表真实的世界暴露场景的环境。通过利用这种增强的模型NM安全评估，我们将能够准确地表征NM的行为和由此产生的bioresponses准确和efficient. Objectives的这个CAREER研究项目是设计，创建和验证一个增强的微环境模型（EMM）的纳米材料的行为和影响的生物准确的评估。为了实现这一目标，PI建议构建和实施EMM，该EMM具有基于细胞的系统的优点，同时结合了关键的生理元素。这些要素包括：1）多细胞区室模型; 2）连接所有细胞区室的动态流; 3）包含循环免疫线;和4）促进3D细胞生长的支架。EMM将加标银NM（AgNM），然后评价和表征纳米材料行为、药代动力学特征、炎症和致突变反应以及细胞应激。对这些终点的分析将使EMM的验证成为可能。

CBET - 1650960 PI: Kristen K. ComfortNanomaterials (NMs) hold tremendous potential to improve quality of life through applications spanning everyday consumer products to biomedical therapeutics. This surge in NM utilization has resulted in significant degrees of NM waste and increased rates of human exposure, generating the need to ensure the safety of NM-based applications. As NM behavior is dependent upon local environmental factors, this creates a challenge for standard cell-based assessment to produce reliable data, as they lack physiological accuracy. This work strives to overcome these limitations by transforming a standard cellular model into one more representative of a human system, thereby developing an environment more representative of real world exposure scenarios. Through utilization of this enhanced model for NM safety assessments, we will be able to accurately characterize NM behavior and resultant bioresponses accurately and efficiently.The objective of this CAREER research project is to design, create, and validate an enhanced microenvironment model (EMM) for biologically accurate evaluation of nanomaterial behavior and impact. To accomplish this, the PI proposes to construct and implement the EMM which has the advantages of cell-based systems, while incorporating the key physiological elements. These elements include: 1) a multiple cellular compartment model; 2) dynamic flow connecting all cellular compartments; 3) a inclusion of a circulating immune line; and 4) a scaffold to promote 3D cellular growth. The EMM will be spiked with silver NMs (AgNMs) followed by evaluation and characterization of nanomaterial behavior, pharmacokinetic profiles, inflammatory and mutagenic responses and cellular stress. Analyses of these endpoints will enable validation of the EMM.