Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX, 77843, USA.
Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, 77030, USA.
Adv Healthc Mater. 2021 Nov;10(21):e2101141. doi: 10.1002/adhm.202101141. Epub 2021 Jul 26.
3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modeling. However, current cell-laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. Here, a new class of nanoengineered hydrogel-based cell-laden bioinks is introduced, that can be printed into 3D, anatomically accurate, multicellular blood vessels to recapitulate both the physical and chemical microenvironments of native human vasculature. A remarkably unique characteristic of this bioink is that regardless of cell density, it demonstrates a high printability and ability to protect encapsulated cells against high shear forces in the bioprinting process. 3D bioprinted cells maintain a healthy phenotype and remain viable for nearly one-month post-fabrication. Leveraging these properties, the nanoengineered bioink is printed into 3D cylindrical blood vessels, consisting of living co-culture of endothelial cells and vascular smooth muscle cells, providing the opportunity to model vascular function and pathophysiology. Upon cytokine stimulation and blood perfusion, this 3D bioprinted vessel is able to recapitulate thromboinflammatory responses observed only in advanced in vitro preclinical models or in vivo. Therefore, this 3D bioprinted vessel provides a potential tool to understand vascular disease pathophysiology and assess therapeutics, toxins, or other chemicals.
3D 生物打印是一种新兴的添加剂制造技术,用于制造用于人类疾病建模的构建体。然而,目前的细胞负载生物墨水缺乏足够的生物相容性、可打印性和结构稳定性,无法将这项技术转化为临床前和临床试验。在这里,引入了一类新的纳米工程水凝胶基细胞负载生物墨水,可以将其打印成 3D 、解剖准确的、多细胞血管,以重现天然人类血管的物理和化学微环境。这种生物墨水的一个非常独特的特点是,无论细胞密度如何,它都表现出很高的可打印性和保护封装细胞免受生物打印过程中高剪切力的能力。3D 打印的细胞保持健康的表型,并在制造后近一个月内保持存活。利用这些特性,纳米工程生物墨水被打印成 3D 圆柱形血管,由内皮细胞和血管平滑肌细胞的共培养物组成,为模拟血管功能和病理生理学提供了机会。在细胞因子刺激和血液灌注后,这种 3D 生物打印的血管能够再现仅在先进的体外临床前模型或体内观察到的血栓炎症反应。因此,这种 3D 生物打印的血管提供了一种潜在的工具,可以了解血管疾病的病理生理学,并评估治疗药物、毒素或其他化学物质。