Stephen J. Florczyk, Mylene H. Simon, Derek Juba, Patrick S. Pine, Sumona Sarkar, Desu Chen, Paula J. Baker, Subhadip Bodhak, Antonio Cardone, Mary C. Brady, Peter Bajcsy, Carl G. Simon Jr.
Three-dimensional (3D) cellular morphotyping is introduced for assessing and comparing the niches provided by biomaterial scaffolds. Many scaffold systems have been advanced to provide synthetic cell niches for tissue engineering and drug screening applications, however there is no method to assess and compare scaffold niches. To overcome this barrier, a strategy for using 3D cell shape measurements to assign a 3D cell morphotype to scaffold niches was developed. Primary human bone marrow stromal cells (hBSMCs) cultured in planar substrate niches yielded cells with flattened morphologies while cells cultured in 3D scaffold niches took on morphologies with greater 3D-character. Multivariate analysis revealed that 3D-character was best described by measuring the cell depth along its shortest axis after aligning cells with a best-fit ellipsoid (gyration tensor). These results identify a defining characteristic for classifying scaffold niches and a measurement strategy to enable rational design of scaffold niches based on cell structure-function relationships.