Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore, 487372, Singapore.
Adv Mater. 2022 Jan;34(1):e2107038. doi: 10.1002/adma.202107038. Epub 2021 Oct 23.
Recapitulation of complex tissues signifies a remarkable challenge and, to date, only a few approaches have emerged that can efficiently reconstruct necessary gradients in 3D constructs. This is true even though mimicry of these gradients is of great importance to establish the functionality of engineered tissues and devices. Here, a composable-gradient Digital Light Processing (DLP)-based (bio)printing system is developed, utilizing the unprecedented integration of a microfluidic mixer for the generation of either continual or discrete gradients of desired (bio)inks in real time. Notably, the precisely controlled gradients are composable on-the-fly by facilely by adjusting the (bio)ink flow ratios. In addition, this setup is designed in such a way that (bio)ink waste is minimized when exchanging the gradient (bio)inks, further enhancing this time- and (bio)ink-saving strategy. Various planar and 3D structures exhibiting continual gradients of materials, of cell densities, of growth factor concentrations, of hydrogel stiffness, and of porosities in horizontal and/or vertical direction, are exemplified. The composable fabrication of multifunctional gradients strongly supports the potential of the unique bioprinting system in numerous biomedical applications.
复杂组织的重建是一项重大挑战，迄今为止，只有少数几种方法能够有效地在 3D 结构中重建必要的梯度。即使模拟这些梯度对于构建具有功能的工程组织和设备非常重要，但事实确实如此。在这里，开发了一种基于可组合梯度数字光处理（DLP）的（生物）打印系统，该系统利用微流混合器的空前集成，实时生成所需（生物）墨水的连续或离散梯度。值得注意的是，通过简单地调整（生物）墨水的流速比，可以实时对精确控制的梯度进行组合。此外，这种设计方式可在更换梯度（生物）墨水时最大程度地减少（生物）墨水的浪费，进一步增强了这种节省时间和（生物）墨水的策略。举例说明了各种平面和 3D 结构，这些结构具有材料、细胞密度、生长因子浓度、水凝胶硬度以及水平和/或垂直方向的孔隙率的连续梯度。多功能梯度的可组合制造强烈支持该独特生物打印系统在众多生物医学应用中的潜力。
