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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.

BACKGROUND The history of allogenic tooth transplantation can be traced back to the 16th century. Although there have been many successful cases, much needs to be better understood and researched prior to the technique being translated to everyday clinical practice. CASE SUMMARY In the present report, we describe a case of allogenic tooth transplantation between a mother and her daughter. The first left maxillary molar of the mother was diagnosed with residual root resorption and needed to be extracted. The 3rd molar of the daughter was used as a donor tooth. Prior to transplantation, a 3D printing system was introduced to fabricate an individualized reamer drill specifically designed utilizing the donor’s tooth as a template. The specific design of our 3D printed bur allowed for the recipient site to better match the donor tooth. With the ability to 3D print in layers, even the protuberance of the root can be matched and 3D printed, thereby minimizing unnecessary bone loss. CONCLUSION Our study is a pioneering case combining 3D printing with allogenic tooth transplantation, which could be able to minimize unnecessary bone loss and improve the implant stability. This article aims to enhance our understanding of allogenic tooth transplantation and 3D printing, and may potentially lead to tooth transplantation being utilized more frequently - especially since transplantations are so commonly utilized in many other fields of medicine with high success rates.

Osteoporosis has been shown to intensify bone loss caused by periodontitis and both share common risk factors. One strategy utilized to manage the disease has been via the release of Sr ions by Strontium Ranelate having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously we have developed and characterized porous Sr‐mesoporous bioactive glass (Sr‐MBG) scaffolds and demonstrated their ability to promote periodontal regeneration when compared to MBG alone. Our group further discovered a splicing factor, heterogeneous nuclear ribonucleoprotein L (hnRNPL), was drastically down‐regulated in periodontal ligament stem cells (PDLCs) stimulated by Sr through the activation of AKT pathway. Furthermore, hnRNPL restrained the osteogenic differentiation of PDLCs through down‐regulating H3K36me3‐specific methyltransferase Setd2. The goal of the present study was to investigate the mechanism of periodontal regeneration stimulated by Sr It was first found that the epigenetic mechanism of splicing factor hnRNPL participated in the osteogenesis processing of PDLCs stimulated by SrCl2. Meanwhile, the different role of hnRNPL and SET domain containing 2 (Setd2) may provide some implication of the treatment of periodontitis patients simultaneously suffering from osteoporosis.

Boron (B), a trace element found in the human body, plays an important role for health of bone by promoting the proliferation and differentiation of osteoblasts. Our research group previously fabricated B-mesoporous bioactive glass (MBG) scaffolds, which successfully promoted osteogenic differentiation of osteoblasts when compared to pure MBG scaffolds without boron. However, the mechanisms of the positive effect of B-MBG scaffolds on osteogenesis remain unknown. Therefore, we performed in-vivo experiments in OVX rat models with pure MBG scaffolds and compared them to B-MBG scaffold. As a result, we found that B-MBG scaffold induced more new bone regeneration compared to pure MBG scaffold and examined genes related to bone regeneration induced by B-MBG scaffold through RNA-seq to obtain target genes and epigenetic mechanisms. The results demonstrated an increased expression and affiliation of Setd7 in the B-MBG group when compared to the MBG group. Immunofluorescent staining from our in vivo samples further demonstrated a higher localization of Setd7 and H3K4me3 in Runx2-positive cells in defects treated with B-MBG scaffolds. KEGG results suggested that specifically Wnt/β-catenin signaling pathway was highly activated in new bone area associated with B-MBG scaffolds. Thereafter, in vitro studies with human bone marrow stem cells (hBMSCs) stimulated by extracted liquid of B-MBG scaffolds was associated with significantly elevated levels of Setd7, as well as H3K4me3 when compared to MBG scaffolds alone. To verify the role of Setd7 in new bone formation in the presence of Boron, Setd7 was knocked down in hBMSCs with stimulation of the extracted liquids of B-MBG or MBG scaffolds. The result showed that osteoblast differentiation of hBMSCs was inhibited when Setd7 was knocked down, which could not be rescued by the extracted liquids of B-MBG scaffolds confirming its role in osteoblast differentiation and bone regeneration. As a histone methylase, Setd7 may be expected to be a potential epigenetic target for new treatment schemes of osteoporosis. Statement of Significance Boron-containing MBG scaffold has already been proved to promote bone regeneration in femoral defects of OVX rats by our research group, however, the epigenetic mechanism of Boron’s positive effects on bone generation remains ill-informed. In our present study, we found an increased expression and affiliation of Setd7 and H3K4me3 in Runx2-positive osteoblasts in vivo. And in vitro, the higher expression of Setd7 enhanced osteogenic differentiation of human BMSCs stimulated by extracted liquids of B-MBG scaffold compared to MBG scaffold, which was associated with the activation of Wnt/β-catenin signaling pathway. Above all, it suggests that Setd7 plays an positive role in osteogenic differentiation and it may become a potential epigenetic target for new schemes for osteoporosis.

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.