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

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.