The Interplay Between Cell Adhesion Cues and Curvature of Cell Adherent Alginate Microgels in Multipotent Stem Cell Culture

Cell-adherent microcarriers are increasingly used to expand multipotent stem cells on a large scale for therapeutic applications. However, the role of the microcarrier properties and geometry on the phenotypic activities of multipotent cells has not been well studied. This study presents a significant interplay of the number of cell adhesion sites and the curvature of the microcarrier in regulating cell growth and differentiation by culturing mesenchymal stem cells on alginate microgels chemically linked with oligopeptides containing the Arg-Gly-Asp (RGD) sequence. Interestingly, the cell growth rate and osteogenic differentiation level were increased with the RGD peptide density. At a given RGD peptide density, the cell growth rate was inversely related to the microgel diameter, whereas the osteogenic differentiation level was minimally influenced. The dependency of the cell growth rate on the microgel diameter was related to changes in shear stresses acting on cells according to simulation. Overall, this study identifies material variables key to regulating cellular activities on microcarriers, and these findings will be useful to designing a broad array of bioactive microcarriers.