Tailoring the Crosslinking and Degradation of Hyaluronic Acid Hydrogels to Enhance Neocartilage Formation by Mesenchymal Stem Cells

Optimization of tissue formation is essential for the success of a tissue engineered scaffold. Crosslinking density affects encapsulated cell viability, initial mechanical properties, and the diffusion of nutrients and waste. Degradation affects scaffold properties, cell-scaffold interactions, and the quantity and distribution of extracellular matrix (ECM) produced by entrapped cells with time [1,2]. Previously, we showed that neocartilage formation by encapsulated chondrocytes is influenced by network structure and properties [3], and that the chemistry of hyaluronic acid (HA) hydrogels supports and promotes the chondrogenic differentiation of mesenchymal stem cells (MSCs) [4]. While others have also investigated the use of HA-based hydrogels for cartilage repair [5,6], by tuning HA network degradation, with the inclusion of hydrolytically degradable components, we show the effects of temporal network structure on scaffold properties and enhanced neocartilage formation. This type of control could help translate tissue engineering technology to clinical applications.