Oxygen generating hydrogels enhance the survival of engineered pulp tissue

Abstract

Objectives: Severe and prolonged hypoxia is the crucial cause of death of the transplanted cells prior to the establishment of functional circulation. In-situ production of oxygen by oxygen-generating scaffolds could generate and deliver oxygen to the adjacent cells independently of blood perfusion, has attracted extensive attention to enhance the survivability of the transplanted cells. Nevertheless, the application of oxygen-generating scaffolds for facilitating dental pulp tissue survival and regeneration is yet to be explored. In this study, gelatin methacryloyl (GelMA), a biocompatible scaffolding material that closely mimic the native extracellular matrix as well as conducive to cell survival and proliferation, was utilized to fabricate oxygen-generating scaffolds by loading various concentrations of CaO2 to enhance the survival of engineered pulp tissue. Methods: The CaO2 distribution, topography, swelling, and porosity of CaO2-GelMA hydrogels were characterized in detail. The release of O2 by the scaffold and the viability, spreading, and proliferation of stem cells from apical papilla (SCAPs) encapsulated in the GelMA hydrogels with various concentrations of CaO2 under hypoxia were then assessed. In addition, pulp-like tissue constructs were engineered into root canals and cell viability within the apical, middle, and coronal portions were evaluated. Results: It showed that 0.5% CaO2-GelMA was sufficient to supply in situ oxygen for maintaining the embedded SCAPs viability for 1 week. Additionally, the 0.5% CaO2-GelMA hydrogels significantly improved the survivability of SCAPs within the coronal portion of the engineered pulp-like constructs within the root canals. Conclusions: This work revealed that 0.5% CaO2-GelMA hydrogels could offer a potential promising scaffold that enhances survival of the embedded SCAPs in endodontic regeneration.