Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, Stoke-on-Trent, United Kingdom.
Optics and Photonics Research Group, Faculty of Engineering, The University of Nottingham, Nottingham, United Kingdom.
Tissue Eng Part A. 2020 Sep;26(17-18):1014-1023. doi: 10.1089/ten.TEA.2020.0027. Epub 2020 May 21.
bone formation by mesenchymal stromal cells encapsulated in type-1 collagen hydrogels is demonstrated after a 28-day culture 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 × 10 cells/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 generating manufactured bone tissue, defining input parameters that yield predictable output measures of tissue maturation. Impact statement This article describes a simple yet powerful quantitative description of tissue-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 determining bone tissue formation.
在 28 天的培养期后，证明了包裹在 1 型胶原水凝胶中的间充质基质细胞的成骨作用。通过 X 射线微计算机断层扫描、组织学和免疫组织化学分析对水凝胶进行分析，这些分析共同证明了水凝胶中的成骨作用与初始胶原浓度以及随后接种细胞的种群密度呈可量化的比例关系。通过在恒定的细胞接种密度（3×10 个细胞/0.3mL 水凝胶）下改变初始胶原浓度，并分别在恒定的胶原浓度（1mg/mL）下改变细胞接种密度来实现这一点。利用这些数据，提出了一个基于细胞接种胶原凝胶观察到的线性收缩动力学的总水凝胶体积和矿化体积的数学模型。通过将数学模型对第 28 天水凝胶和矿化体积的预测与实验数据进行比较，对模型参数进行拟合。然后，该模型用于预测一系列水凝胶胶原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了全面的输入/输出描述符。提出这种定量方法将是生成人造骨组织的有用工具，确定产生组织成熟可预测输出度量的输入参数。影响说明本文通过将实验数据与数学建模相结合，对组织工程骨进行了简单而强大的定量描述。本文的总体目标是研究目前已知的细胞介导的胶原收缩，并证明通过选择特定的细胞接种密度和胶原水凝胶浓度作为输入参数，可以利用这种现象来定制骨形成。我们的研究利用了一种临床相关的细胞来源（人骨髓间充质干细胞）和一种已获得监管部门批准用于人体的生物材料（1 型胶原），因此可能对临床应用有用，并进一步了解细胞/细胞外基质相互作用在决定骨组织形成中的作用。
