In Situ Oxygen Generation Enhances the SCAP Survival in Hydrogel Constructs

Abstract

Prolonged and severe hypoxia is the main cause of death of transplanted cells prior to the establishment of functional circulation. In situ generation of oxygen by oxygen-producing scaffolds—a unique solution that could produce and deliver oxygen to the adjacent cells independently of blood perfusion—has attracted considerable attention to enhance the survivability of the transplanted cells. However, the application of oxygen-generating scaffolds for facilitating cell survival in pulp-like tissue regeneration is yet to be explored. In this study, gelatin methacryloyl (GelMA)—a biocompatible scaffolding material that closely mimics the native extracellular matrix and is conducive to cell proliferation and differentiation—was used to fabricate oxygen-generating scaffolds by loading various concentrations of CaO2. The CaO2 distribution, topography, swelling, and pore size 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 evaluated. In addition, cellular constructs were engineered into root canals, and cell viability within the apical, middle, and coronal portions was assessed. Our findings showed that 0.5% CaO2-GelMA was sufficient to supply in situ oxygen for maintaining the embedded SCAP viability for 1 wk. Furthermore, the 0.5% CaO2-GelMA hydrogels improved the survivability of SCAPs within the coronal portion of the engineered cellular constructs within the root canals. This work demonstrated that 0.5% CaO2-GelMA hydrogels offer a potential promising scaffold that enhances survival of the embedded SCAPs in endodontic regeneration.

The Journey of SCAPs (Stem Cells from Apical Papilla), from Their Native Tissue to Grafting: Impact of Oxygen Concentration

“…Alternatively, providing oxygen to the grafted tissue could be pertinent. For example, it has been shown that in situ oxygenation of SCAPs embedded in a hydrogel like GelMa in the presence of CAO 2 results in improved graft survival [ 75 ]. In the same vein, in situ oxygen generation by oxygen-producing scaffolds could produce and deliver oxygen to the adjacent cells independently of blood perfusion.…”

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds

“…In addition, making oxygen-containing hydrogels is also a preferable choice. Zou et al [ 201 ] produced a gelatin methacrylate (GelMA) hydrogel containing calcium peroxide to release oxygen in situ to ensure the average growth of SCAP under a hypoxic environment.…”

Oxygen-Generating Biomaterials for Translational Bone Regenerative Engineering

“…Therefore, the cell viability of the hydrogel with 0.5% was higher than that of GelMa after 4 and 7 days. However, the burst release of oxygen resulted in oxidative stresses that damaged cells, so samples with higher CPO had lower cell viability (Figure D) …”

“…(D) Confocal images and semiquantification of live (green)/dead (red) stained stem cells from apical papilla encapsulated in CaO 2 –GelMA hydrogels containing 0%, 0.5%, 1%, or 3% CaO 2 in hypoxic conditions on days 1, 4, and 7. The scale bar equals 100 μm . (A) Reproduced with permission from ref , Copyright 2020 J. Biomed.…”