Development and Characterization of Thermoresponsive Double-Network Nanocomposite Hydrogel for Bone Tissue Engineering

Abstract

In this study, a thermoresponsive double-network (DN) nanocomposite hydrogel is developed. The primary hydrogel network comprises Pluronic P123, while the secondary network comprises gelatinmethacrylate (GELMA) and polyacrylamide (PAM). A systematic approach is adopted to develop DN hydrogels. Initially, the impact of Pluronic P123 concentrationon the mechanical properties of PAM-GELMA hydrogel is investigated. Results from the tensile strength and the oscillatory shear tests reveal that an increasing P123 concentration has a marginal effect on the storage modulus while significantly reducing the loss modulus of the PAM-GELMA hydrogel, thereby improving mechanical properties. Notably, DN3 hydrogel containing 7.5w/v% P123 in PAM-GELMA exhibits osteoid matrix-like mechanical properties. To further enhance the mechanical properties, citrate-containing amorphous calcium phosphate (ACP_CIT) is incorporated in DN3 hydrogel at varying concentrations. At a lower concentration of ACP_CIT (0.75 w/v%), the mechanical properties of DN3-ACP0.75 hydrogel are notably enhanced. Incorporating ACP_CIT in DN3 hydrogel (DN3-ACP0.75) decreases creep strain, rapid stress relaxation, and reduced water uptake capacity while maintaining the thermoresponsive behavior. Finally, an in vitro analysis confirms the cytocompatibility of the hydrogels with MC3T3-E1 cells, indicating the potential use in bone tissue engineering.