Florczyk Stephen J, Simon Mylene, Juba Derek, Pine P Scott, Sarkar Sumona, Chen Desu, Baker Paula J, Bodhak Subhadip, Cardone Antonio, Brady Mary C, Bajcsy Peter, Simon Carl G
Biophysics Program, University of Maryland, College Park, Maryland 20742, United States.
ACS Biomater Sci Eng. 2017 Oct 9;3(10):2302-2313. doi: 10.1021/acsbiomaterials.7b00473. Epub 2017 Sep 19.
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 L-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.
许多生物材料支架已得到改进，可为组织工程和药物筛选应用提供合成细胞微环境；然而，目前比较支架微环境的方法侧重于细胞功能结果，或试图使不同支架形式之间的材料特性标准化。我们展示了一种三维（3D）细胞形态分型策略，用于比较不同生物材料支架形式之间的生物材料支架细胞微环境。将原代人骨髓基质细胞（hBMSCs）培养在8种不同的生物材料支架上，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。采用生物信息学方法，通过使用82个形状指标分析约1000个细胞，确定每个处理组的3D细胞形态型。我们发现，在平面基质上培养的hBMSCs产生平面细胞形态型，而在3D支架中培养的细胞具有更高的伸长或等轴细胞形态型。多变量分析有效地区分了扁平基质中细胞与支架中细胞的平均形状，L深度指标（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细胞形态分型技术能够直接比较广泛不同类型支架之间的细胞微环境，并基于细胞结构-功能关系设计支架。
