Locally Released H2 and O2 from an Artificial Periosteum Modulate the Survival and Reparative Activities of Stem Cells Derived from the Aged Human Nasal Mucosa after Transplantation

Stem cell therapies are limited by poor cell survival and engraftment. Elderly diabetic patients (EDPs) have a greater risk of bone graft failure. Herein, a g-C 3 N 4 /polydopamine (PDA@g-C 3 N 4 ) composite nanosheet was successfully fabricated via in situ polymerization of PDA on a g-C 3 N 4 surface. Then, the PDA/g-C 3 N 4 composite was crosslinked with a fibrin hydrogel to prepare an artificial periosteum for EDPs. With the help of NIR, we showed that the synthetic artificial periosteum released H 2 and O 2 and enhanced the survival and osteogenic differentiation of aged human nasal mucosa-derived ectodermal stem cells (hEMSCs) in microenvironments characterized by oxidative stress and hypoxia. The artificial periosteum had pleiotropic effects on aged hEMSC reparative activities, modulating cytokine secretion and the protein expression of effectors associated with vascularization, and bone formation in vivo. Our findings imply that the developed artificial periosteum loaded with hEMSCs has great promise for the repair of bone defects in EDPs.