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Abstract Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss®) to replace autograft, and used cytokine (BMP-2) to enhance osteogenesis. Encouragingly, this mixture, which we named “Autograft Mimic (AGM)”, has multiple functions and advantages. (1) The fiber network provided by PRF binds the entire bone scaffold together, thereby shaping the bone grafts and maintaining the space of the defect area. (2) The sustained release of BMP-2 from bone graft promoted bone regeneration continuously. (3) AGM recruited bone marrow mesenchymal stem cells (BMSCs) and promote their proliferation, migration, and osteogenic differentiation. Thus, AGM developed in this study can improve osteogenesis, and provide new guidance for the development of clinical bone grafts.

Macrophages have been found to regulate the effects of biomaterials throughout the entire tissue repair process as an antigen-presenting cell. As a well-defined osteoconductive biomaterial for bone defect regeneration, tricalcium phosphate (TCP) has been found to facilitate a favourable osteoimmunomodulatory response that can shift macrophage polarization towards the M2 phenotype. In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Furthermore, the NF-κB pathway in macrophages was significantly downregulated through stimulation of TCP, suggesting a potential interaction between EZH1 and the NF-κB pathway. Utilizing gene knock-down therapy in macrophages, it was found that depletion of EZH1 induced M2 macrophage polarization but did not downregulate NF-κB. When the NF-κB pathway was inhibited, the expression of EZH1 was significantly downregulated, suggesting that the inhibition of EZH1 may be regulated by the NF-κB pathway. These novel findings provide valuable insights into a potential gene target system that controls M2 macrophage polarization which ultimately favours a microenvironment suitable for bone repair.