Tissue Eng Regen Med.  2023 Oct;20(6):981-992. 10.1007/s13770-023-00561-w.

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

• Ye Y
• Zhong H
• Huang S
• Lai W
• Huang Y
• Sun C
• Zhang Y
• Zheng S

• KMID: 2546845
• DOI: http://doi.org/10.1007/s13770-023-00561-w

Abstract

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 MnO₂ nanoparticles as a protective carrier (MnO₂ @Pol/HA hydrogel) for delivering BMSCs.
RESULTS
The resulting MnO₂ @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 MnO₂ @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., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF).
CONCLUSION
This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO₂ @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Keyword

Hydrogel; BMSCs; Oxidative stress; Bone regeneration; Osteoporosis