Predicting Bone Formation in Mesenchymal Stromal Cell-Seeded Hydrogels Using Experiment-Based Mathematical Modeling.
Predicting Bone Formation in Mesenchymal Stromal Cell-Seeded Hydrogels Using Experiment-Based Mathematical Modeling.
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使用基于实验的数学模型预测间充质基质细胞接种的水凝胶中的骨形成。
DOI：
10.1089/ten.tea.2020.0027
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发表时间：
2020
影响因子：
--
通讯作者：
Price JC
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文献类型：
--
作者：
Price JC
体外培养28天后，1型胶原水凝胶包封的间充质基质细胞体外形成骨。通过X射线显微计算机断层扫描、组织学和免疫组织化学对水凝胶进行分析，这共同证明水凝胶中的骨形成与初始胶原蛋白浓度成定量比例，随后与接种细胞的群体密度成比例。通过在恒定细胞接种密度（3 × 105个细胞/0.3 mL水凝胶）下改变初始胶原蛋白浓度，并在恒定胶原蛋白浓度（1 mg/mL）下分别改变细胞接种密度，确定了这一点。使用这些数据，基于观察到的细胞接种胶原蛋白凝胶的线性收缩动力学，提出了总水凝胶体积和矿化体积的数学模型。通过将第28天的水凝胶和矿化体积的数学模型的预测与实验数据进行比较来拟合模型参数。然后，该模型用于预测一系列水凝胶胶原蛋白浓度和细胞接种密度的水凝胶和矿化体积，为骨组织工程生成矿化水凝胶提供全面的输入/输出描述符。有人提出，这种定量的方法将是一个有用的工具generatingin vitromanufactured骨组织，定义输入参数，产生可预测的输出measures of tissue maturity.Impact statementThis article介绍了一个简单而强大的定量描述ofin vitrotissue-engineered骨相结合的实验数据与数学建模。本文的总体目的是研究目前已知的细胞介导的胶原蛋白收缩，并证明这种现象可以通过选择一组特定的细胞接种密度和胶原蛋白水凝胶浓度形式的输入参数来定制骨形成。我们的研究利用了临床相关的细胞来源（人间充质干细胞）与生物材料，已获得监管机构批准用于人类（1型胶原蛋白），因此可能是有用的临床应用，以及进一步了解细胞/细胞外基质相互作用，以确定在vitrobone组织形成。
In vitrobone formation by mesenchymal stromal cells encapsulated in type-1 collagen hydrogels is demonstrated after a 28-dayin vitroculture period. Analysis of the hydrogels is carried out by X-ray microcomputed tomography, histology, and immunohistochemistry, which collectively demonstrates that bone formation in the hydrogels was quantifiably proportional to the initial collagen concentration, and subsequently the population density of seeded cells. This was established by varying the initial collagen concentration at a constant cell seeding density (3 × 105cells/0.3 mL hydrogel), and separately varying cell seeding density at a constant collagen concentration (1 mg/mL). Using these data, a mathematical model is presented for the total hydrogel volume and mineralization volume based on the observed linear contraction dynamics of cell-seeded collagen gels. The model parameters are fitted by comparing the predictions of the mathematical model for the hydrogel and mineralized volumes on day 28 with the experimental data. The model is then used to predict the hydrogel and mineralization volumes for a range of hydrogel collagen concentrations and cell seeding densities, providing comprehensive input/output descriptors for generating mineralized hydrogels for bone tissue engineering. It is proposed that this quantitative approach will be a useful tool for generatingin vitromanufactured bone tissue, defining input parameters that yield predictable output measures of tissue maturation.Impact statementThis article describes a simple yet powerful quantitative description ofin vitrotissue-engineered bone by combining experimental data with mathematical modeling. The overall aim of the article is to examine what is currently known about cell-mediated collagen contraction, and demonstrate that this phenomenon can be exploited to tailor bone formation by choosing a specific set of input parameters in the form of cell seeding density and collagen hydrogel concentration. Our study utilizes a clinically relevant cell source (human mesenchymal stem cells) with a biomaterial that has received regulatory approval for use in humans (collagen type 1), and hence could be useful for clinical applications, as well as furthering our understanding of cell/extracellular matrix interactions in determiningin vitrobone tissue formation.