Zhu Xiaolu, Yang Hao
College of Mechanical & Electrical Engineering, Hohai University, Changzhou 213022, Jiangsu, China.
Changzhou Key Laboratory of Digital Manufacture Technology, Hohai University, Changzhou 213022, Jiangsu, China.
Micromachines (Basel). 2018 Mar 2;9(3):109. doi: 10.3390/mi9030109.
Four-dimensional (4D) biofabrication techniques aim to dynamically produce and control three-dimensional (3D) biological structures that would transform their shapes or functionalities with time, when a stimulus is imposed or cell post-printing self-assembly occurs. The evolution of 3D branching patterns via self-assembly of cells is critical for the 4D biofabrication of artificial organs or tissues with branched geometry. However, it is still unclear how the formation and evolution of these branching patterns are biologically encoded. Here, we study the biofabrication of lung branching structures utilizing a simulation model based on Turing instability that raises a dynamic reaction⁻diffusion (RD) process of the biomolecules and cells. The simulation model incorporates partial differential equations of four variables, describing the tempo-spatial distribution of the variables in 3D over time. The simulation results present the formation and evolution process of 3D branching patterns over time and also interpret both the behaviors of side-branching and tip-splitting as the stalk grows and the fabrication style under an external concentration gradient of morphogen, through 3D visualization. This provides a theoretical framework for rationally guiding the 4D biofabrication of lung airway grafts via cellular self-organization, which would potentially reduce the complexity of future experimental research and number of trials.
四维（4D）生物制造技术旨在动态地制造和控制三维（3D）生物结构，当施加刺激或细胞打印后自组装发生时，这些结构会随时间改变其形状或功能。通过细胞自组装实现三维分支模式的演变对于具有分支几何形状的人工器官或组织的4D生物制造至关重要。然而，这些分支模式的形成和演变如何在生物学上编码仍不清楚。在这里，我们利用基于图灵不稳定性的模拟模型研究肺分支结构的生物制造，该模型引发了生物分子和细胞的动态反应-扩散（RD）过程。该模拟模型包含四个变量的偏微分方程，描述了这些变量在三维空间中随时间的时空分布。模拟结果呈现了三维分支模式随时间的形成和演变过程，并通过三维可视化解释了随着茎的生长侧支和尖端分裂的行为以及在形态发生素的外部浓度梯度下的制造方式。这为通过细胞自组织合理指导肺气道移植物的4D生物制造提供了一个理论框架，这可能会降低未来实验研究的复杂性和试验次数。
