The interactions between cells and the extracellular matrix are vital for the self-organisation of tissues. In this paper we present proof-of-concept to use machine learning tools to predict the role of this mechanobiology in the self-organisation of cell-laden hydrogels grown in tethered moulds. We develop a process for the automated generation of mould designs with and without key symmetries. We create a large training set with $N=6500$ cases by running detailed biophysical simulations of cell-matrix interactions using the contractile network dipole orientation (CONDOR) model for the self-organisation of cellular hydrogels within these moulds. These are used to train an implementation of the \texttt{pix2pix} deep learning model, reserving $740$ cases that were unseen in the training of the neural network for training and validation. Comparison between the predictions of the machine learning technique and the reserved predictions from the biophysical algorithm show that the machine learning algorithm makes excellent predictions. The machine learning algorithm is significantly faster than the biophysical method, opening the possibility of very high throughput rational design of moulds for pharmaceutical testing, regenerative medicine and fundamental studies of biology. Future extensions for scaffolds and 3D bioprinting will open additional applications.
翻译:细胞与细胞外基质之间的相互作用对于组织的自我组织至关重要。在本文中,我们提出使用机器学习工具来预测这种力学生物学在细胞负载的水凝胶中的作用,该水凝胶在被拴住的模具中生长。我们开发了一个流程来自动化设计具有和不具有关键对称性的模具。我们使用自我组织细胞水凝胶的机械生物学模型(称为CONDOR)运行详细的仿真,创建了一个大的训练集,共$N=6500$个案例。这些用于训练\texttt{pix2pix}深度学习模型的实现,保留了$740$个案例,这些案例在神经网络的训练和验证中未被看到。将机器学习技术的预测与生物物理算法的预测进行比较表明,机器学习算法进行了出色的预测。机器学习算法比生物物理方法快得多,可以极高的通量合理设计模具用于制药测试、再生医学和基础生物学的研究。未来的扩展为支架和3D生物打印将开启更多应用。