Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Adv Mater. 2018 Jul;30(27):e1800242. doi: 10.1002/adma.201800242. Epub 2018 May 7.
A stereolithography-based bioprinting platform for multimaterial fabrication of heterogeneous hydrogel constructs is presented. Dynamic patterning by a digital micromirror device, synchronized by a moving stage and a microfluidic device containing four on/off pneumatic valves, is used to create 3D constructs. The novel microfluidic device is capable of fast switching between different (cell-loaded) hydrogel bioinks, to achieve layer-by-layer multimaterial bioprinting. Compared to conventional stereolithography-based bioprinters, the system provides the unique advantage of multimaterial fabrication capability at high spatial resolution. To demonstrate the multimaterial capacity of this system, a variety of hydrogel constructs are generated, including those based on poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacryloyl (GelMA). The biocompatibility of this system is validated by introducing cell-laden GelMA into the microfluidic device and fabricating cellularized constructs. A pattern of a PEGDA frame and three different concentrations of GelMA, loaded with vascular endothelial growth factor, are further assessed for its neovascularization potential in a rat model. The proposed system provides a robust platform for bioprinting of high-fidelity multimaterial microstructures on demand for applications in tissue engineering, regenerative medicine, and biosensing, which are otherwise not readily achievable at high speed with conventional stereolithographic biofabrication platforms.
提出了一种基于立体光刻的生物打印平台,用于制造多材料的异质水凝胶结构。通过数字微镜器件进行动态图案设计,与移动台和包含四个通/断气动阀的微流控装置同步,用于创建 3D 结构。新型微流控装置能够在不同的(细胞负载)水凝胶生物墨水之间快速切换,实现逐层多材料生物打印。与传统的基于立体光刻的生物打印机相比,该系统提供了在高空间分辨率下进行多材料制造的独特优势。为了展示该系统的多材料能力,生成了各种水凝胶结构,包括基于聚乙二醇二丙烯酸酯(PEGDA)和明胶甲基丙烯酰(GelMA)的结构。通过将细胞负载的 GelMA 引入微流控装置并制造细胞化结构,验证了该系统的生物相容性。进一步评估了 PEGDA 框架的图案和三种不同浓度的 GelMA(负载血管内皮生长因子)在大鼠模型中的新生血管化潜力。所提出的系统为按需生物打印高保真度多材料微结构提供了一个强大的平台,可用于组织工程、再生医学和生物传感等应用,而这些应用在传统的立体光刻生物制造平台上则难以高速实现。