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

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Tissue Engineering and Regenerative Medicine Aims and scope

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., 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 MnO2@Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

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Data availability

The data that support the findings of this study are accessible from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the Foundation of Guangdong Basic and Applied Basic Research Foundation (2022A1515140046 & 2022A1515140151 & 2022A1515140071) and Huizhou Priority Clinical Speciality Cultivation Project (Orthopedics and Sports Medicine) and Scientific Research Projects of Guangdong Provincial Bureau of Traditional Chinese Medicine (20221400 & 20222241) and Research and Innovation Fund of Huizhou First Hospital (2022ZD001 & 2022ZD002) and Huizhou Science and Technology Project (2022CZ010146 & 2022CZ010423).

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Author notes

  1. Yuanjian Ye, Haobo Zhong, and Shoubin Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedic, Huizhou First Hospital, Guangdong Medical University, Huizhou, 516003, Guangdong, China

    Yuanjian Ye, Haobo Zhong, Shoubin Huang, Weiqiang Lai, Chunhan Sun & Shaowei Zheng

  2. Department of Emergency Medicine, Huizhou First Hospital, Guangdong Medical University, Huizhou, 516003, Guangdong, China

    Yanling Zhang

  3. Guangdong Medical University, DongGuan, 523000, Guangdong, China

    Yizhi Huang

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  1. Yuanjian Ye
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Correspondence to Yanling Zhang or Shaowei Zheng.

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The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of the Huizhou First Hospital, Guangdong Medical University (IACUC no. 2021113).

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Ye, Y., Zhong, H., Huang, S. et al. Reactive Oxygen Species Scavenging Hydrogel Regulates Stem Cell Behavior and Promotes Bone Healing in Osteoporosis. Tissue Eng Regen Med 20, 981–992 (2023). https://doi.org/10.1007/s13770-023-00561-w

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