Cytocompatibility of hyaluronic acid hydrogels with concentration variations

BACKGROUND: Hydrogel, which is a kind of semi-solid materials, can be used for three-dimensional culture for mesenchymal stem cells. So it would improve efficiency of cultured cells by eliminating "contact inhibition", which is common in two-dimensional culture. Hyaluronic acid hydrogel as a three-dimensional culture matrix has been reported in the field of stem cells and tissue engineering research. OBJECTIVE: To investigate the morphology and proliferation of rat bone marrow mesenchymal stem cells cultured in the three-dimensional hyaluronic acid hydrogels with different properties. METHODS: Three concentrations of hyaluronic acid hydrogels, 4, 8, and 12 g/L, were prepared and evaluated with their properties including gelation time, swelling ratio, degradation rate and viscoelasticity. Rat bone marrow mesenchymal stem cells were encapsulated and cultured in those hyaluronic acid hydrogels. Another rat bone marrow mesenchymal stem cells cultured in the two-dimensional medium served as control. Morphology of the encapsulated bone marrow mesenchymal stem cells was observed by laser scanning confocal microscope. Growth curves of bone marrow mesenchymal stem cells cultured in the hyaluronic acid hydrogels with different concentrations were depicted using cell counting method. RESULTS AND CONCLUSION: The higher concentration of hyaluronic acid hydrogels leaded to the shorter gelation time, lower swelling ratio, slower degradation rate and higher strength (P < 0.05). Bone marrow mesenchymal stem cells cultured in the three-dimensional hyaluronic acid hydrogels showed a spherical shape and higher proliferation compared with those in normal culture. Meanwhile, rat bone marrow mesenchymal stem cells cultured in 8 g/L hyaluronic acid hydrogels showed higher proliferation than those in 4 and 12 g/L hyaluronic acid hydrogels (P < 0.05). These findings indicate that concentration variations of hyaluronic acid hydrogels lead to changes in their mechanical properties. Hyaluronic acid hydrogel with a concentration of 8 g/L is more appropriate for three-dimensional culture of rat bone marrow mesenchymal stem cells.