Calcium peroxide-mediated in situ formation of multifunctional hydrogels with enhanced mesenchymal stem cell behaviors and antibacterial properties

Abstract

Injectable hydrogels can serve as therapeutic vehicles and implants for the treatment of various diseases as well as for tissue repair/regeneration. In particular, the horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂)-catalyzed hydrogelation system has attracted much attention, due to its ease of handling and controllable gel properties. In this study, we introduce calcium peroxide (CaO₂) as a H₂O₂-generating reagent to gradually supply a radical source for the HRP-catalyzed crosslinking reaction. This novel therapy can create stiff hydrogels without compromising the cytocompatibility of the hydrogels due to the use of initially high concentrations of H₂O₂. The physico-chemical properties of the hydrogels can be controlled by varying the concentrations of HRP and CaO₂. In addition, the controlled and sustained release of bioactive molecules, including H₂O₂, O₂, and Ca²⁺ ions, from the hydrogels could stimulate the cellular behaviors (attachment, migration, and differentiation) of human mesenchymal stem cells. Moreover, the hydrogels exhibited killing efficacy against both Gram-negative and Gram-positive bacteria, dependent on the H₂O₂ and Ca²⁺ release amounts. These positive results suggest that hydrogels formed by HRP/CaO₂ can be used as potential matrices for a wide range of biomedical applications, such as bone regeneration and infection treatment.