Biomimetic and immunomodulatory baicalin-loaded graphene oxide-demineralized bone matrix scaffold for in vivo bone regeneration

Abstract

The use of an artificial bone substitute is a potential strategy for repairing bone defects; however, the inadequate consideration of repair–immune system interactions, resulting in significant pathological changes in the microenvironment, is a major barrier to achieving effective regenerative outcomes. Here, we evaluated a biomimetic baicalin (BAI)-incorporating graphene oxide-demineralized bone matrix (GO–BAI/DBM) hybrid scaffold, which was beneficial for bone regeneration. First, by considering that bone is a kind of organic–inorganic composite, a biomimetic GO/DBM bone substitute with enhanced physiochemical and osteoinductive properties was fabricated. Furthermore, inherently therapeutic GO was also used as a drug delivery carrier to achieve the sustained and prolonged release of BAI. Notably, a series of experiments showed that the GO–BAI nanocomposites could transform inflammatory M1 macrophages into pro-healing M2 macrophages, which was beneficial for in vitro angiogenesis and osteogenesis. By using a rat subcutaneous model, it was revealed that the GO–BAI nanocomposites proactively ameliorated the inflammatory response, which was coupled with decreased fibrous encapsulation. Notably, obvious in situ calvarial bone regeneration was achieved using the GO–BAI/DBM hybrid scaffold. These findings demonstrated that the bifunctional GO–BAI/DBM scaffold, by enhancing beneficial cross-talk among bone cells and inflammatory cells, might be utilized as an effective strategy for bone regeneration.