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

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

• Processed pyritum
• Metal ions
• Hydrogel
• Osteoimmunomodulatory effects
• Macrophages
• Bone regeneration