MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
Biomacromolecules. 2023 Feb 13;24(2):604-612. doi: 10.1021/acs.biomac.2c00961. Epub 2023 Feb 1.
Three-dimensional cell culture in engineered hydrogels is increasingly used in tissue engineering and regenerative medicine. The transfer of nutrients, gases, and waste materials through these hydrogels is of utmost importance for cell viability and response, yet the translation of diffusion coefficients into practical guidelines is not well established. Here, we combined mathematical modeling, fluorescent recovery after photobleaching, and hydrogel diffusion experiments on cell culture inserts to provide a multiscale practical approach for diffusion. We observed a dampening effect of the hydrogel that slowed the response to concentration changes and the creation of a diffusion gradient in the hydrogel by media refreshment. Our designed model combined with measurements provides a practical point of reference for diffusion coefficients in real-world culture conditions, enabling more informed choices on hydrogel culture conditions. This model can be improved in the future to simulate more complicated intrinsic hydrogel properties and study the effects of secondary interactions on the diffusion of analytes through the hydrogel.
三维细胞培养在工程水凝胶中越来越多地用于组织工程和再生医学。这些水凝胶中营养物质、气体和废物的传递对于细胞活力和反应至关重要，但扩散系数转化为实际指南的方法尚未得到很好的建立。在这里，我们结合数学建模、光漂白后荧光恢复和细胞培养插入物上的水凝胶扩散实验，提供了一种用于扩散的多尺度实用方法。我们观察到水凝胶的阻尼效应，该效应减缓了对浓度变化的响应，并通过介质更新在水凝胶中产生扩散梯度。我们设计的模型结合测量结果，为实际培养条件下的扩散系数提供了实用的参考点，使人们能够在水凝胶培养条件方面做出更明智的选择。该模型可以在未来进行改进，以模拟更复杂的内在水凝胶特性，并研究二次相互作用对分析物通过水凝胶扩散的影响。
