A graphene oxide-loaded processed pyritum composite hydrogel for accelerated bone regeneration via mediation of M2 macrophage polarization

Changcan Shi; Yinting Yu; Hongjuan Wu; Huanjin Liu; Mengyu Guo; Wenxin Wang; Dan Wang; Chenxu Wei; Hao Zhai; Guojun Yan; Zhipeng Chen; Ting Cai; Weidong Li

doi:10.1016/j.mtbio.2023.100753

A graphene oxide-loaded processed pyritum composite hydrogel for accelerated bone regeneration via mediation of M2 macrophage polarization

Mater Today Bio. 2023 Jul 30:22:100753. doi: 10.1016/j.mtbio.2023.100753. eCollection 2023 Oct.

Authors

Changcan Shi¹, Yinting Yu¹, Hongjuan Wu^{2

3}, Huanjin Liu¹, Mengyu Guo¹, Wenxin Wang¹, Dan Wang⁴, Chenxu Wei¹, Hao Zhai⁵, Guojun Yan¹, Zhipeng Chen¹, Ting Cai⁵, Weidong Li^{1

6}

Affiliations

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
² The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
³ Department of Pulmonology, Jiangning Hospital of Traditional Chinese Medicine, Nanjing, 211100, China.
⁴ School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100089, China.
⁵ State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
⁶ Key Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, Nanjing, 210023, China.

Abstract

A coordinated interaction between osteogenesis and the osteoimmune microenvironment plays a vital role in regulating bone healing. However, disturbances in the pro- and anti-inflammatory balance hinder the therapeutic advantages of biomaterials. In this study, a novel composite hydrogel was successfully fabricated using graphene oxide (GO)-loaded processed pyritum (PP) in combination with poly(ethylene glycol) diacrylate (PEGDA) and carboxymethyl chitosan (CMC). Subsequently, the immunomodulatory effects and bone regenerative potential of PP/GO@PEGDA/CMC were investigated. The results demonstrated that the PP/GO@PEGDA/CMC hydrogel possessed excellent mechanical properties, swelling capacity, and stability. Moreover, PP/GO@PEGDA/CMC prominently promoted M2 polarization and increased the levels of anti-inflammatory factors (interleukin (IL)-4, IL-10, and transforming growth factor-β). These beneficial effects facilitated the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Additionally, the in vivo results further verified that the implantation of PP/GO@PEGDA/CMC markedly reduced local inflammation while enhancing bone regeneration at 8 weeks post-implantation. Therefore, the results of this study provide potential therapeutic strategies for bone tissue repair and regeneration by modulating the immune microenvironment.

Keywords: Bone regeneration; Hydrogel; Macrophages; Metal ions; Osteoimmunomodulatory effects; Processed pyritum.