Optimization of macromer density in human MSC-laden hyaluronic acid (HA) hydrogels

Mesenchymal stem cells are attractive cell type and can undergo chondrogenesis in various 3D platforms. Hyaluronic acid (HA) hydrogel, a natural constituent of the cartilage extracellular matrix, provides a biologically relevant interface for encapsulated cells. While MSC-laden HA constructs can produce native mechanical properties using cells from animal sources, clinical repair will depend on successful translation of these findings to human MSCs (hMSCs). To optimize chondrogenesis, we assessed the ability of hMSCs to undergo chondrogenesis in varying macromer concentration HA gels. Variation in this parameter influenced construct mechanical and biochemical properties. In 1% methacrylated HA (MeHA), equilibrium modulus and GAG content were higher (86kPa (E_Y) and 2.16%) than in 2% MeHA constructs (50 kPa, 1.62% GAG). However, greater contractility occurred in 1% MeHA (-36.25%/-24.25%; Thickness/diameter) compared to 2% MeHA (-20.57%/1.02%) constructs. This study provides new insight into optimized macromer densities for hMSC-based cartilage tissue engineering using HA hydrogels.