Role of Pericellular Matrix in Mesenchymal Stem Cell Deformation during Chondrogenic Differentiation

One approach widely used in tissue engineering research, particularly for compressive load-bearing tissues, has been to embed progenitor cells in a hydrogel scaffold. Because these cells are exposed to mechanical loading either during culture or when implanted, understanding the biophysical mechanisms that regulate cell deformation in these systems could help enhance the efficiency of construct maturation. This study investigates the role of the pericellular matrix (PCM) in the deformability of human mesenchymal stem cells (hMSCs) in hydrogels during chondrogenesis. Results show that type VI collagen accumulated regionally around cells after 1 week and fully enveloped cells by 2 weeks of chondrogenic alginate bead culture, but was minimally deposited around cells in growth media. The PCM was able to attenuate cell deformations significantly only when type VI collagen coverage was complete. Gene expression data show that sox9 was upregulated when non-differentiating cells were embedded in alginate, but not sustained unless supplemented with pro-chondrogenic factors. In addition, we examined cell deformations with disruption of individual cytoskeletal elements, but could not detect significant effects. Overall, these finding suggest that the PCM is the primary modulator of cell deformation during chondrogenic differentiation of hMSCs. These considerations will be important for defining loading strategies and designing scaffold properties.