Many biomaterial scaffolds have been advanced to provide synthetic cell niches for tissue engineering and drug screening applications; however, current methods for comparing scaffold niches focus on cell functional outcomes or attempt to normalize materials properties between different scaffold formats. We demonstrate a three-dimensional (3D) cellular morphotyping strategy for comparing biomaterial scaffold cell niches between different biomaterial scaffold formats. Primary human bone marrow stromal cells (hBMSCs) were cultured on 8 different biomaterial scaffolds, including fibrous scaffolds, hydrogels, and porous sponges, in 10 treatment groups to compare a variety of biomaterial scaffolds and cell morphologies. A bioinformatics approach was used to determine the 3D cellular morphotype for each treatment group by using 82 shape metrics to analyze approximately 1000 cells. We found that hBMSCs cultured on planar substrates yielded planar cell morphotypes, while those cultured in 3D scaffolds had elongated or equiaxial cellular morphotypes with greater height. Multivariate analysis was effective at distinguishing mean shapes of cells in flat substrates from cells in scaffolds, as was the metric L₁-depth (the cell height along its shortest axis after aligning cells with a characteristic ellipsoid). The 3D cellular morphotyping technique enables direct comparison of cellular microenvironments between widely different types of scaffolds and design of scaffolds based on cell structure–function relationships.

中文翻译：

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用于评估生物材料支架利基的生物信息学 3D 细胞形态分析策略


许多生物材料支架已得到改进，可以为组织工程和药物筛选应用提供合成细胞生态位；然而，目前比较支架生态位的方法侧重于细胞功能结果或尝试标准化不同支架格式之间的材料特性。我们展示了一种三维（3D）细胞形态分析策略，用于比较不同生物材料支架格式之间的生物材料支架细胞生态位。原代人骨髓基质细胞（hBMSC）在8种不同的生物材料支架上培养，包括纤维支架、水凝胶和多孔海绵，分为10个处理组，以比较各种生物材料支架和细胞形态。使用生物信息学方法通过使用 82 个形状指标分析大约 1000 个细胞来确定每个治疗组的 3D 细胞形态类型。我们发现在平面基质上培养的 hBMSC 产生平面细胞形态类型，而在 3D 支架中培养的 hBMSC 则产生具有更高高度的细长或等轴细胞形态类型。多变量分析可以有效地区分平坦基质中的细胞与支架中的细胞的平均形状，度量L ₁深度（将细胞与特征椭球体对齐后沿其最短轴的细胞高度）也是如此。 3D细胞形态分型技术可以直接比较不同类型支架之间的细胞微环境，并根据细胞结构-功能关系设计支架。