3D bioprinted cardiac tissue models

在人体临床试验期间，很大比例的候选药物因为不安全或无效而失败。即使临床前的细胞和动物研究似乎是阳性的，问题也会出现，因为在这些模型上用药物进行的测试通常不能预测在人类身上会发生什么。这在很大程度上是由于不同物种在生物学上的显著差异。例如，离子通道(心脏细胞传导电流的膜蛋白)在人类和动物之间可能会有所不同。包括非心血管药物在内的许多药物都针对心脏中的这些离子通道，这可能会导致致命的心律失常。因此，使用临床前模型来更好地预测药物安全性是至关重要的。为了简化治疗开发流程，我们将开发一种新的3D生物打印人类心脏活动模型，该模型将改进翻译科学过程，以预测药物在人类身上是否安全有效。我们的目标是开发出与脉冲传导和心律失常发生相关的、与人体心脏电生理特性密切相关的3D人类心脏组织结构(S)。我们将使用一种已知的模仿人类心脏细胞的HL-1细胞系，以及新的基于微流体的3D生物打印技术和方法来构建3D心脏组织。最终，这些模型有望取代使用动物筛选药物的安全性和有效性。为了验证我们的模型，我们将评估一系列已知化合物的心脏毒性潜力，并将结果与使用当前标准分析获得的数据进行比较。一种新药的开发和上市批准平均需要超过25亿美元。仅完成临床前研究就需要大约1亿美元。使用新的心脏组织生物打印模型有望显著缩短将新药推向市场的成本和时间。

During human clinical trials, a large percentage of candidate drugs fail because they are unsafe or ineffective.Even when pre-clinical cell and animal studies seem positive, problems occur because tests done with drugs onthese models are often not predictive of what happens in humans. Much of this is due to significant differencesin biology between species.For instance, ion channels (membrane proteins through which heart cells conduct electrical currents) can varybetween humans and animals. Many drugs, including non-cardiovascular drugs, target these ion channels in theheart, which can potentially result in lethal arrhythmias. Thus, it is critical to use preclinical models that canclosely reproduce what happens in humans to better predict drug safety.To streamline the therapeutic development pipeline, we will develop a novel 3D bioprinted human cardiactissue model which will improve the translational science process for predicting whether drugs will be safe andeffective in humans. The goal is to develop 3D human cardiac tissue structure(s) that closely model theelectrophysiological properties of the human heart, relevant to impulse conduction and arrhythmia generation.We will use a known cardiac cell line, HL-1, that mimics human cardiac cells and and novel microfluidic based3D bioprinting technology and methodologies to build the 3D cardiac tissue. Ultimately, these models areexpected to replace the use of animals to screen drugs for safety and efficacy.To validate our models, we will evaluate the cardiotoxicity potential of a range of known compounds, andcompare the outcome with data obtained using current standard assays. It takes on average over $2.5 billion todevelop and gain marketing approval for a new drug. About $100 million is required to complete thepre-clinical studies alone. Using novel bioprinted models of cardiac tissue is expected to significantly cut thecost and time of bringing a new drug to market.