Reactive Oxygen Species Scavenging Hydrogel Regulates Stem Cell Behavior and Promotes Bone Healing in Osteoporosis

Background: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. Methods: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO 2 nanoparticles as a protective carrier (MnO 2 @Pol/HA hydrogel) for delivering BMSCs. Results: The resulting MnO 2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO 2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g . , TNF-α, IL-1β, and IL-6) and osteogenic related factors (e.g., TGF-β and PDGF). Conclusion: This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO 2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.