Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany.
Biomater Adv. 2023 Apr;147:213329. doi: 10.1016/j.bioadv.2023.213329. Epub 2023 Feb 8.
During nozzle-based bioprinting, like inkjet and microextrusion, cells are subjected to hydrostatic pressure for up to several minutes. The modality of the bioprinting-related hydrostatic pressure is either constant or pulsatile depending on the technique. We hypothesized that the difference in the modality of hydrostatic pressure affects the biological response of the processed cells differently. To test this, we used a custom-made setup to apply either controlled constant or pulsatile hydrostatic pressure on endothelial and epithelial cells. Neither bioprinting procedure visibly altered the distribution of selected cytoskeletal filaments, cell-substrate adhesions, and cell-cell contacts in either cell type. In addition, pulsatile hydrostatic pressure led to an immediate increase of intracellular ATP in both cell types. However, the bioprinting-associated hydrostatic pressure triggered a pro-inflammatory response in only the endothelial cells, with an increase of interleukin 8 (IL-8) and a decrease of thrombomodulin (THBD) transcripts. These findings demonstrate that the settings adopted during nozzle-based bioprinting cause hydrostatic pressure that can trigger a pro-inflammatory response in different barrier-forming cell types. This response is cell-type and pressure-modality dependent. The immediate interaction of the printed cells with native tissue and the immune system in vivo might potentially trigger a cascade of events. Our findings, therefore, are of major relevance in particular for novel intra-operative, multicellular bioprinting approaches.
在基于喷嘴的生物打印中，如喷墨和微挤压，细胞会受到长达几分钟的静水压力。生物打印相关的静水压力的方式要么是恒定的，要么是脉动的，这取决于技术。我们假设，静水压力方式的差异会以不同的方式影响处理细胞的生物学反应。为了验证这一点，我们使用了一种定制的装置，对内皮细胞和上皮细胞施加控制的恒定或脉动的静水压力。这两种生物打印过程都没有明显改变所选细胞骨架丝、细胞-基底附着和细胞-细胞接触在两种细胞类型中的分布。此外，脉动的静水压力会立即增加两种细胞类型的细胞内 ATP。然而，只有内皮细胞对生物打印相关的静水压力产生了促炎反应，白细胞介素 8（IL-8）的增加和血栓调节蛋白（THBD）转录物的减少。这些发现表明，基于喷嘴的生物打印过程中采用的设置会产生静水压力，这种压力会在不同的屏障形成细胞类型中引发促炎反应。这种反应取决于细胞类型和压力方式。打印细胞与体内天然组织和免疫系统的即时相互作用可能会引发一系列事件。因此，我们的发现对于新型术中、多细胞生物打印方法尤其重要。
