Maji Somnath, Lee Minkyoung, Lee Jooyoung, Lee Jaehee, Lee Hyungseok
Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Republic of Korea.
Department of Animal Industry Convergence, Kangwon National University, Chuncheon, Republic of Korea.
Mater Today Bio. 2023 Jul 8;21:100723. doi: 10.1016/j.mtbio.2023.100723. eCollection 2023 Aug.
Hepatic sinusoids are uniquely organized structures that help maintain a spectrum of hepatic functions. Although several in vitro liver models have been developed to replicate liver sinusoids, most of these platforms require complex, multi-step fabrication methods making it difficult to achieve truly three-dimensional (3D) channel geometries. In this study, a single-step bioprinting technique was demonstrated to simultaneously print a chip platform and develop a perfusable vascularized liver sinusoid in vitro model. The integrated system uses a co-axial-based bioprinting approach to develop a liver sinusoid-like model that consists of a sacrificial core compartment containing a perfusable pre-vascular structure and an alginate-collagen-based shell compartment containing hepatocytes. The lumen-based perfusable 3D liver sinusoid-on-a-chip (LSOC-P) demonstrated significantly better hepatocyte viability, proliferation, and liver-specific gene and protein expression compared to a 3D hepatocyte-based core/shell model with static media and the standard hepatocyte-based 2D sandwich culture system. A drug toxicity evaluation of hepatotoxins highlighted the comparatively higher sensitivity of the LSOC system with a close estimation of the therapeutic range of safe drug concentrations for humans. In conclusion, the current findings indicate that the combinatorial single-step co-axial bioprinting technique is a promising fabrication approach for the development of a perfusable LSOC platform for drug screening applications.
肝血窦是独特的组织结构，有助于维持一系列肝脏功能。尽管已经开发了几种体外肝脏模型来复制肝血窦，但这些平台大多需要复杂的多步骤制造方法，难以实现真正的三维（3D）通道几何形状。在本研究中，展示了一种单步生物打印技术，可同时打印芯片平台并开发一种可灌注的血管化肝血窦体外模型。该集成系统采用基于同轴的生物打印方法来开发一种类似肝血窦的模型，该模型由一个包含可灌注预血管结构的牺牲性核心隔室和一个包含肝细胞的藻酸盐 - 胶原蛋白基外壳隔室组成。与具有静态培养基的基于3D肝细胞的核/壳模型和基于标准肝细胞的2D夹心培养系统相比，基于管腔的可灌注3D肝血窦芯片（LSOC-P）显示出显著更好的肝细胞活力、增殖以及肝脏特异性基因和蛋白质表达。对肝毒素的药物毒性评估突出了LSOC系统相对较高的敏感性，能够紧密估计人类安全药物浓度的治疗范围。总之，目前的研究结果表明，组合单步同轴生物打印技术是开发用于药物筛选应用的可灌注LSOC平台的一种有前途的制造方法。
