Buenzli Pascal R, Lanaro Matthew, Wong Cynthia S, McLaughlin Maximilian P, Allenby Mark C, Woodruff Maria A, Simpson Matthew J
School of Mathematical Sciences, Queensland University of Technology (QUT), Brisbane, Australia.
School of Mechanical Medical and Process Engineering, Queensland University of Technology (QUT), Brisbane, Australia.
Acta Biomater. 2020 Sep 15;114:285-295. doi: 10.1016/j.actbio.2020.07.010. Epub 2020 Jul 13.
Tissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.
生物支架中的组织生长受到孔隙几何形状的显著影响，但这种几何依赖性如何从细胞增殖和细胞迁移等动态细胞过程中产生，目前仍知之甚少。在这里，我们研究了孔径对在薄的3D打印支架中桥接孔隙所需时间的影响。实验表明，在强大的曲率控制下，新组织从孔隙周边不断填充孔隙，这导致组织前沿随时间逐渐变圆。尽管在这个演化过程中组织呈现出各种形状，但我们发现桥接一个孔隙的时间仅仅与总体孔径呈线性增加。为了在这个实验观察中区分细胞行为的生物学影响和几何形状的机制影响，我们基于细胞向孔隙的多孔-费希尔侵入提出了一个简单的组织生长反应-扩散模型。首先，该模型对组织的演化提供了很好的定性描述；模型中的新组织以取决于组织基质局部曲率的有效速率生长。其次，该模型表明桥接时间与孔径的线性依赖关系仅由几何原因引起，而不是由于不同大小孔隙间细胞行为的差异。我们的分析表明，这些实验结构中的组织生长动力学受影响集体细胞增殖和迁移过程的机制拥挤效应主导，并且可以通过具有稳健、一致行为的细胞简单反应-扩散模型进行预测。
