Bioinnovation Program, Tulane University, New Orleans, LA, United States of America. Department of Biomedical Engineering, Tulane University, New Orleans, LA, United States of America.
Biofabrication. 2019 Oct 21;12(1):015002. doi: 10.1088/1758-5090/ab41b4.
The high attrition rate of neuro-pharmaceuticals as they proceed to market necessitates the development of clinically-relevant in vitro neural microphysiological systems that can be utilized during the preclinical screening phase to assess the safety and efficacy of potential compounds. Historically, proposed models have adhered to two distinct approaches; those that are biologically relevant (e.g.-organoids, spheroids) or those that provide engineering control (e.g.-bioprinting, microfluidics). Separately, these approaches fail to fully recapitulate the complex hierarchical structure of the nervous system, limiting their clinical applications. Furthermore, the reliance on manual implementation present in many models fails to effectively scale up or satisfy the consistency standards required for widespread industry adoption. This work serves as a proof-of-concept for merging the two approaches to create a neural microphysiological system that overcomes their individual limitations. Spinal cord spheroids, fabricated using magnetic nanoparticles, are positioned in a three-dimensional hydrogel construct using magnetic bioprinting. Resulting constructs demonstrate both localized cell-cell interactions and long-distance projections that mimic in vivo structure. The use of magnetic nanoparticles for spheroid formation provides batch-to-batch consistency in size and shape and reduces the reliance on trained experimenters for accurate placing for culture. Taken together, this combination approach provides the first steps towards developing a simple approach for integrating spheroid, hydrogel culture, and bioprinting as an alternative to more specialized and expensive processes.
神经药物在进入市场的过程中淘汰率很高，这就需要开发具有临床相关性的体外神经微生理系统，以便在临床前筛选阶段评估潜在化合物的安全性和有效性。从历史上看，提出的模型采用了两种截然不同的方法；那些具有生物学相关性的（例如类器官、球体）或提供工程控制的（例如生物打印、微流控）。这些方法单独使用都不能完全再现神经系统的复杂层次结构，限制了它们的临床应用。此外，许多模型中手动实施的依赖关系不能有效地扩大规模或满足广泛行业采用所需的一致性标准。这项工作是将两种方法结合起来创建一个克服其各自局限性的神经微生理系统的概念验证。使用磁性纳米粒子制造的脊髓球体使用磁性生物打印放置在三维水凝胶结构中。得到的结构显示出局部细胞-细胞相互作用和长距离投射，模拟了体内结构。磁性纳米粒子用于球体形成提供了批次间的尺寸和形状一致性，并减少了对训练有素的实验人员进行准确放置培养的依赖。总之，这种组合方法为开发一种简单的方法提供了初步步骤，即将球体、水凝胶培养和生物打印集成在一起，作为更专业和昂贵工艺的替代方法。
