Background: Bone regeneration is a well‐regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process.Objective: This review aims to summarize the role of the T‐helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering.Results: The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano‐structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration.Conclusion: Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.

Demineralized dentin matrix (DDM) is an osteoconductive and osteoinductive material that has been successfully used in sinus floor augmentation and alveolar ridge augmentation in clinical applications. It releases bone morphogenetic proteins (BMPs) and other growth factors, making DDM a suitable grafting material. However, the granular particle of DDM makes it difficult to anchor into the bone defect area. The aim of this study was to investigate the biological effects and osteoinductivity of the combination of DDM and Fibrin Glue (FG) at an optimal ratio on bone healing from a critical bone defect in an animal model. The mouse osteoblastic cell line (MC3T3-E1) was co-cultured with various ratios of DDM and FG to examine their effects on osteoblast proliferation and differentiation, as indicated by alkaline phosphatase (ALP) activity, osteocalcin (OC) production and mineralized nodules formation. The optimal ratio was then chosen for further study with a rabbit calvarial defective model, in which they were implanted with DDM or DDM-FG1 (1 g: 0.1 ml) and DDM-FG2 (1 g: 0.5 ml) compounds, or left blank for 2, 4, 8 and 12 weeks to investigate soft tissue and new bone regeneration. Micro-CT and histology analysis were used to evaluate the total grafting properties according to the different healing periods. The result from in vitro studies demonstrated that the ratio of 1:0.1 induced more ALP activity and mineralized nodules, while the ratio of 1: 0.5 (DDM-FG combined) induced more osteocalcin (OC) at specific time points. In the animal model, the 3D new bone volume in all DDM-FG treatment groups was significantly greater than that in the blank group at 2, 4, 8 and 12 weeks. Furthermore, the new bone volume was greater in DDM-FG2 when compared to the other groups during the early weeks of the healing period. In histological analysis, clusters of osteoblasts were formed adjacent to the DDM particles, and newly formed bone was observed in all groups, suggesting an osteoinductive property of DDM. Moreover, the greater new collagen synthesis observed at 4 weeks suggested that early bone healing was induced in the DDM-FG2 group. This study demonstrated that at an optimal ratio, the DDM-FG compound enhances osteogenic activities and bone regeneration.

Alveolar hypoplasia in Ectodermal Dysplasia (ED) children poses unique challenges for implant treatment compared to those with missing teeth from trauma or other congenital disorders. This study aimed to summarize and evaluate the clinical evidence regarding the feasibility of implant treatment in young patients with ED. The systematic review (PROSPERO registration number: CRD42024600172) adhered to PRISMA guidelines and conducted searches on PubMed, Scopus, Web of Science, and Google Scholar to retrieve articles published between 1994 and 2024. Inclusion criteria focused on identifying studies specifically addressing implant treatment in children with ED. The risk of bias was evaluated using the Joanna Briggs Institute checklist. The review encompassed 3 retrospective studies, 1 prospective study, 4 case series, and 15 case reports, involving a total of 46 patients aged 3 to 18 years. Among these patients, the highest implant survival rates were observed in the age group of 8 to 13 years, while the lowest rates were noted in the 3 to 8 years age group. The predominant complications identified included the necessity for prosthesis remake or relining and alterations in implant positioning, which can typically be addressed through surgical interventions and adjustments to the prosthesis. Throughout the dental implant treatment of ED children, the complications relevant to growth and development are inevitable yet manageable, potentially leading to a favorable treatment success rate. However, given the substantial constraints posed by the existing clinical data, the benefit-to-risk ratio of implant therapy in ED children warrants further observation and evaluation.

Demineralised dentin matrix (DDM) is an effective scaffold material for bone tissue engineering. However, the osteoimmunological mechanism of DDM remains unexplored. Th17/Treg cell balance has been noticed as a crucial factor in bone regeneration. The aim of this research is to elucidate the influence of DDM on the balance of Th17/Treg and its underlying molecular mechanisms. The study examined DDM's effects on Th17/Treg cell balance by co-incubating DDM extract with peripheral blood mononuclear cells (PBMCs). Transcriptomics and bioinformatics identified DDM-related differentially expressed genes. A naïve CD4⁺ T cell-bone marrow-derived mesenchymal stem cells (BMSCs) co-culture model assessed DDM's immunomodulatory effects on Th17/Treg differentiation and their impact on BMSC viability and osteogenic differentiation. In vivo, a rabbit mandibular defect model with DDM implantation evaluated bone repair and Th17/Treg regulation. DDM promoted Treg cell differentiation in PBMCs and increased anti-inflammatory cytokines. Transcriptomic analysis shows that indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of Th17/Treg balance. In naïve CD4⁺ T cells, DDM enhanced Treg differentiation, which was blocked by IDO1 inhibition. This immunomodulation improved BMSCs viability and osteogenic differentiation which was attenuated by IDO1 inhibition. Co-culture with naïve CD4⁺ T cells further amplified DDM's pro-osteogenic effects. In rabbit mandibular defects, DDM enhanced bone repair and was suppressed with IDO1 inhibition. This study demonstrates that DDM regulates the Th17/Treg cell balance by promoting Treg cell differentiation through IDO1 upregulation, with minimal impact on Th17 cells. This immunomodulatory mechanism is a key factor underlying DDM's significant role in bone repair.