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.Comfort纳米材料(NMS)具有巨大的潜力，可以通过从日常消费品到生物医学疗法的应用来提高生活质量。NM使用率的这种激增导致了NM浪费的严重程度和人类接触比率的增加，因此需要确保基于NM的应用程序的安全。由于NM的行为依赖于当地的环境因素，这给基于细胞的标准评估带来了挑战，因为它们缺乏生理准确性，无法产生可靠的数据。这项工作努力克服这些限制，将标准的细胞模型转换为更能代表人类系统的模型，从而开发出更能代表真实世界暴露场景的环境。通过利用这种用于纳米材料安全评估的增强模型，我们将能够准确而高效地描述纳米材料的行为和由此产生的生物响应。本职业研究项目的目标是设计、创建和验证一个增强的微环境模型(EMM)，用于对纳米材料的行为和影响进行生物学上的准确评估。为了实现这一点，PI建议构建和实现EMM，它具有基于细胞系统的优势，同时包含关键的生理元素。这些元素包括：1)多细胞隔间模型；2)连接所有细胞隔间的动态流；3)包含循环免疫线；以及4)促进3D细胞生长的支架。将在EMM中添加银纳米颗粒(AgNms)，然后评估和表征纳米材料的行为、药代动力学、炎症和突变反应以及细胞应激。对这些端点的分析将使EMM得以验证。

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.