Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9, Canada.
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 0A3, Canada.
Adv Healthc Mater. 2022 Dec;11(23):e2201346. doi: 10.1002/adhm.202201346. Epub 2022 Oct 17.
Bioelastomers are extensively used in biomedical applications due to their desirable mechanical strength, tunable properties, and chemical versatility; however, three-dimensional (3D) printing bioelastomers into microscale structures has proven elusive. Herein, a high throughput omnidirectional printing approach via coaxial extrusion is described that fabricates perfusable elastomeric microtubes of unprecedently small inner diameter (350-550 µm) and wall thickness (40-60 µm). The versatility of this approach is shown through the printing of two different polymeric elastomers, followed by photocrosslinking and removal of the fugitive inner phase. Designed experiments are used to tune the microtube dimensions and stiffness to match that of native ex vivo rat vasculature. This approach affords the fabrication of multiple biomimetic shapes resembling cochlea and kidney glomerulus and affords facile, high-throughput generation of perfusable structures that can be seeded with endothelial cells for biomedical applications. Post-printing laser micromachining is performed to generate micro-sized holes (520 µm) in the tube wall to tune microstructure permeability. Importantly, for organ-on-a-chip applications, the described approach takes only 3.6 min to print microtubes (without microholes) over an entire 96-well plate device, in contrast to comparable hole-free structures that take between 1.5 and 6.5 days to fabricate using a manual 3D stamping approach.
生物弹性体由于其理想的机械强度、可调的性能和化学多功能性,被广泛应用于生物医学领域;然而,将生物弹性体 3D 打印成微尺度结构一直难以实现。本文描述了一种通过共轴挤压实现高通量各向同性打印的方法,可制造出前所未有的小内径(350-550μm)和壁厚(40-60μm)的可灌注弹性微管。通过打印两种不同的聚合物弹性体,随后进行光交联和去除易挥发的内相,展示了这种方法的多功能性。通过设计实验来调整微管的尺寸和刚度,使其与天然的离体大鼠血管相匹配。这种方法可以制造出多种仿生形状,如耳蜗和肾小球,并可以轻松、高通量地生成可灌注的结构,这些结构可以接种内皮细胞用于生物医学应用。在打印后进行激光微加工,在管壁上生成微尺寸的孔(520μm),以调节微结构的渗透性。重要的是,对于器官芯片应用,与使用手动 3D 冲压方法制造无孔结构相比,所描述的方法仅需 3.6 分钟即可在整个 96 孔板设备上打印微管(无微孔),而制造无孔结构则需要 1.5 到 6.5 天。