Alveolar bone reconstruction simulation is an effective means for quantifying orthodontics, but currently, it is not possible to directly obtain human alveolar bone material models for simulation. This study introduces a prediction method for the equivalent shear modulus of three-dimensional random porous materials, integrating the first-order Ogden hyperelastic model to construct a computed tomography (CT) based porous hyperelastic Ogden model (CT-PHO) for human alveolar bone. Model parameters are derived by combining results from micro-CT, nanoindentation experiments, and uniaxial compression tests. Compared to previous predictive models, the CT-PHO model shows a lower root mean square error (RMSE) under all bone density conditions. Simulation results using the CT-PHO model parameters in uniaxial compression experiments demonstrate more accurate prediction of the mechanical behavior of alveolar bone under compression. Further prediction and validation with different individual human alveolar bone samples yield accurate results, confirming the generality of the CT-PHO model. The study suggests that the CT-PHO model proposed in this paper can estimate the material properties of human alveolar bone and may eventually be used for bone reconstruction simulations to guide clinical treatment.
Humans ; Tomography, X-Ray Computed/methods* ; Porosity ; Alveolar Process/physiology* ; Bone Density ; Computer Simulation ; Elasticity ; X-Ray Microtomography ; Stress, Mechanical ; Finite Element Analysis ; Models, Biological

Complex crown-root fractures in the esthetic zone refer to a type of dental trauma occurring in the anterior region, characterized by concurrent fractures involving both the crown and the root, with associated pulp exposure and periodontal tissue injury. These injuries consistently exhibit critical anatomical features, including a fixed palatal fracture location below the alveolar crest, compromised residual tooth structure, and frequent encroachment of the biological width. To predict treatment outcomes, a risk assessment framework based on the restoration-tooth-periodontium interface was developed. Resistance risk was evaluated by assessing the type of residual dentin ferrule and the length of the root within the alveolar bone, while periodontal risk was assessed according to gingival phenotype and alveolar bone morphology. Based on these risk dimensions and the principles of aesthetics, stability, and minimally invasive treatment, a diagnostic classification system was established to categorize fractures into three types: favorable, intervention and high-risk. Type-specific management strategies were proposed: for favorable cases, crown lengthening combined with deep margin elevation to reduce periodontal risk is recommended; for intervention cases, orthodontic extrusion or surgical extrusion is applied to simultaneously address both ferrule deficiency and biological width violation; for high-risk cases, extraction followed by implant restoration is advised due to limited root preservation value. The presented classification enables clinicians to adopt a scientific and structured approach to treatment planning for these complex crown-root fractures in the aesthetic zone.
Humans ; Tooth Fractures/therapy* ; Tooth Root/injuries* ; Risk Assessment ; Tooth Crown/injuries* ; Periodontium ; Esthetics, Dental ; Dental Restoration, Permanent/methods*

OBJECTIVE: To evaluate the clinical and radiographic efficacy of micro crestal flap-alveolar ridge preservation following extraction of mandibular molars with severe periodontitis compared with natural healing, and to preliminarily propose the surgical indication. METHODS: A retrospective analysis was conducted on clinical data from patients with mandibular molars with severe periodontitis either receiving micro crestal flap-alveolar ridge preservation (MCF-ARP group) or undergoing natural healing in department of periodontology, Peking University School and Hospital of Stomatology from September 2013 to June 2021. Cone-beam computed tomography scannings performed before/immediately after extraction (as baseline) and repeated before implantation (after the extraction socket healing) were used to measure the ridge width, height and volumetric changes of the sockets, and the proportion of guided bone regeneration (GBR) during implant therapy were compared between the two groups. RESULTS: Between baseline and healing, significant differences in changes of MCF-ARP group [(8.34±2.81) mm] and natural healing group [(3.82±3.58) mm] in the distances from mandibular canal to center of the tooth socket were recorded (P < 0.001). The ridge width at 1 mm below the most coronal aspect of the crest increased by (3.50±4.88) mm in the MCF-ARP group but decreased by (0.16±5.70) mm in the natural healing group, respectively (P=0.019). After healing, the MCF-ARP group showed the distances from mandibular canal to center of the tooth socket >8 mm in all the cases, with 97.1% exceeding 10 mm. Natural healing group displayed 23.1% of the cases with center bone height < 8 mm and 61.5% exceeding 10 mm. Volume changes at the buccal and lingual aspect as well as the total socket were significantly greater in the MCF-ARP group compared with natural healing group (P < 0.001).At the time of implantation, GBR was performed in 5 out of 68 subjects (8.3%) in the MCF-ARP group, whereas 8 out of 26 subjects (30.8%) in the natural healing group required GBR, reflecting significant difference (P=0.003). CONCLUSION In the sites of mandibular molars with severe periodontitis, when the distances from mandibular canal to center of the tooth socket was not enough (less than 7 mm), clinicians could consider performing the micro crestal flap-alveolar ridge preservation to achieve augmentation for alveolar ridge and reduce the proportion of guided bone regeneration during implant therapy to reduce the difficulty and risk of injuries during implant therapy.
Humans ; Tooth Extraction ; Retrospective Studies ; Surgical Flaps ; Molar/surgery* ; Mandible/surgery* ; Female ; Periodontitis/surgery* ; Male ; Adult ; Middle Aged ; Cone-Beam Computed Tomography ; Alveolar Ridge Augmentation/methods* ; Alveolar Process/surgery* ; Tooth Socket/diagnostic imaging* ; Dental Implantation, Endosseous/methods*

OBJECTIVE: To evaluate the wound healing of recipient and donor sites following keratinized mucosa augmentation (KMA) around implants in reconstructed jaw areas and to compare these outcomes with gingival grafts in native jawbone, so as to provide clinical guidance for postoperative maintenance, and to investigate the impact of clinical experience on the evaluation of KMA postoperative healing through subgroup comparisons. METHODS: This study included patients who underwent resection of maxillofacial tumors, fibular or iliac flap reconstruction, and implant placement at Peking University Dental Hospital from October 2020 to April 2023. Three months post-implant placement, the patients were referred for KMA procedures. Clinical photographs of the reconstructed area were taken preoperatively, immediately postoperatively, and 3 weeks and 3 months post-surgery. Additionally, photographs of the palatal donor site were obtained preoperatively and 3 weeks later. Wound healing was assessed by four junior and three senior clinicians utilizing the early healing index (EHI), early wound healing score (EHS), and pink esthetic score (PES).And senior clinicians evaluated the healing effect compared with gingival transplantation on natural jawbone using a 10-point scale. RESULTS: A total of 26 patients with jawbone reconstruction were included, with an average age of (34.2±10.2) years, 11 males (42.3%) and 15 females (57.7%). Among them, 13 cases (50.0%) underwent fibula flap reconstruction, and 13 cases (50.0%) underwent iliac flap reconstruction. The average number of implants per patient was 3.2±0.7. In the recipient area, 3 weeks postoperatively, the EHS was 7.0 (4.0, 9.0), with sub-item scores as follows: Clinical signs of re-epithelialization (CSR) 6.0 (3.0, 6.0), clinical signs of haemostasis (CSH) 1.5 (1.0, 2.0), and clinical signs of inflammation (CSI) 1.0 (0.0, 1.0), indicating that the average appearance of the wound in the recipient area was characterized by generally well-approximated wound edges with minimal fibrin lines and mild erythema and swelling. The EHI for the recipient area was 2.0 (1.5, 2.5), suggesting that the incision was mostly closed with some fibrin lines 3 weeks postoperatively. The long-term healing evaluation system, PES, was 2.5 (2.0, 3.0), with sub-scores for color [1.0 (1.0, 1.5)] and texture [1.5 (1.0, 2.0)], which were slightly different from the reference values.In the palatal donor area, 3 weeks postoperatively, the EHI score was lower at 1.3 (1.0, 2.5), while the EHS score was higher at 8.5 (6.0, 10.0), indicating better soft tissue healing in the donor area compared with the recipient area. Among the clinicians with different levels of experience, the assessment of wound healing revealed that except for the CSI sub-item, where the junior group scored higher than the senior group, all other sub-items showed significantly higher scores in the senior group compared with the junior group. In the EHS evaluation system, the CSH sub-item demonstrated no significant differences between the groups with varying levels of experience. Experienced clinicians' evaluation outcomes of healing effect compared with gum graft on natural alveolar bone was 8.5 (7.5, 9.5), showing high consistency [intraclass correlation coefficient (ICC): 0.892; 95% confidence interval (CI): 0.791－0.949], suggesting slightly suboptimal healing results after KMA surgery. CONCLUSION The healing process following KMA in the context of jawbone reconstruction is relatively protracted, emphasizing the necessity for comprehensive postoperative management. Moreover, clinician experience plays a significant role in the assessment of wound healing outcomes for KMA in maxillofacial reconstruction.
Humans ; Wound Healing ; Adult ; Male ; Female ; Gingiva/transplantation* ; Plastic Surgery Procedures/methods* ; Middle Aged ; Surgical Flaps ; Keratins

Dental stem cells (DSCs), a distinct subset of mesenchymal stem cells (MSCs), are isolated from dental tissues, such as dental pulp, exfoliated deciduous teeth, periodontal ligament, and apical papilla. They have emerged as a promising source of stem cell therapy for tissue regeneration and autoimmune disorders. The main types of DSCs include dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Each type exhibits distinct advantages: easy access via minimally invasive procedures, multi-lineage differentiation potential, and excellent ethical acceptability. DSCs have demonstrated outstanding clinical efficacy in oral and maxillofacial regeneration, and their long-term safety has been verified. In oral tissue regeneration, DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair. A defining advantage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration, which render them a better option for oral tissue regenerative therapies. Beyond oral applications, DSCs also exhibit promising potential in the treatment of systemic diseases, including type Ⅱ diabetes and autoimmune diseases due to their immunomodulatory effects. Moreover, extracellular vesicles (EVs) derived from DSCs act as critical mediators for DSCs' paracrine functions. Possessing regulatory properties similar to their parental cells, EVs are extensively utilized in research targeting tissue repair, immunomodulation, and regenerative therapy-offering a "cell-free" strategy to mitigate the limitations associated with cell-based therapies. Despite these advancements, standardizing large-scale manufacturing, maintaining strict quality control, and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use. Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy. In conclusion, DSCs and their EVs represent a transformative approach in regenerative medicine, and increasing clinical evidence supports their application in oral and systemic diseases. Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.
Humans ; Dental Pulp/cytology* ; Translational Research, Biomedical ; Mesenchymal Stem Cells/cytology* ; Periodontal Ligament/cytology* ; Stem Cells/cytology* ; Regeneration ; Tooth, Deciduous/cytology* ; Cell Differentiation ; Tissue Engineering/methods* ; Regenerative Medicine

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.
Animals ; Bone Regeneration/drug effects* ; Rats ; Periodontal Ligament/cytology* ; Microspheres ; NF-E2-Related Factor 2 ; Hydrogels ; Periodontitis/therapy* ; Osteogenesis/drug effects* ; Disease Models, Animal ; Stem Cells ; Male ; Rats, Sprague-Dawley ; Humans

The periodontal ligament (PDL) plays a crucial role in transmitting and dispersing occlusal force, acting as mechanoreceptor for muscle activity during chewing, as well as mediating orthodontic tooth movement. It transforms mechanical stimuli into biological signals, influencing alveolar bone remodeling. Recent research has delved deeper into the biological and mechanical aspects of PDL, emphasizing the importance of understanding its structure and mechanical properties comprehensively. This review focuses on the latest findings concerning both macro- and micro- structural aspects of the PDL, highlighting its mechanical characteristics and factors that influence them. Moreover, it explores the mechanotransduction mechanisms of PDL cells under mechanical forces. Structure-mechanics-mechanotransduction interplay in PDL has been integrated ultimately. By providing an up-to-date overview of our understanding on PDL at various scales, this study lays the foundation for further exploration into PDL-related biomechanics and mechanobiology.
Periodontal Ligament/cytology* ; Humans ; Biomechanical Phenomena ; Mechanotransduction, Cellular/physiology* ; Stress, Mechanical

The repair of the periodontal membrane is essential for the successful management of periodontal disease and dental trauma. Emdogain^® (EMD) is widely used in periodontal therapy due to its ability to promote repair. Despite substantial research, the cellular and molecular mechanisms underlying EMD's effects, particularly at the single-cell resolution, remain incompletely understood. This study established a delayed tooth replantation model in rats to investigate these aspects. Tooth loss rate and degree of loosening were evaluated at 4 and 8 weeks. Micro-CT, HE staining, TRAP staining, and immunofluorescence staining were evaluated to assess EMD's efficacy. Single-cell sequencing analyses generated single-cell maps that explored enrichment pathways, cell communication, and potential repair mechanisms. Findings indicated that EMD could reduce the rate of tooth loss, promote periodontal membrane repair, and reduce root and bone resorption. Single-cell analysis revealed that EMD promotes the importance of Vtn+ fibroblasts, enhancing matrix and tissue regeneration functions. Additionally, EMD stimulated osteogenic pathways, reduced osteoclastic activity, and promoted angiogenesis-related pathways, particularly bone-related H-type vessel expression in endothelial cells. Gene modules associated with angiogenesis, osteogenesis, and odontoblast differentiation were identified, suggesting EMD might facilitate osteogenesis and odontoblast differentiation by upregulating endothelium-related genes. Immune cell analysis indicated that EMD did not elicit a significant immune response. Cell communication analysis suggested that EMD fostered pro-regenerative networks driven by interactions between mesenchymal stem cells, fibroblasts, and endothelial cells. In conclusion, EMD proves to be an effective root surface therapy agent that supports the restoration of delayed replantation teeth.
Animals ; Tooth Replantation/methods* ; Rats ; Dental Enamel Proteins/pharmacology* ; Single-Cell Analysis ; Rats, Sprague-Dawley ; X-Ray Microtomography ; Osteogenesis/drug effects* ; Male ; Periodontal Ligament/drug effects*

Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications. In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner. However, existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes, thereby hindering a comprehensive understanding of their interactions. Here, we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria, respectively. Using a key oral pathobiont, Fusobacterium nucleatum, as the primary test bed, we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes. Compared to conventional models, this system enhanced bacterial invasion, elevated intracellular bacterial loads, and elicited more robust host pro-inflammatory responses, including increased secretion of CXCL10, IL-6, and IL-8. In addition, the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens. Finally, we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont, Porphyromonas gingivalis. These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics, offering a physiologically relevant approach to advance oral and systemic health research.
Coculture Techniques/methods* ; Humans ; Fusobacterium nucleatum/physiology* ; Gingiva/microbiology* ; Keratinocytes/microbiology* ; Host Microbial Interactions ; Mouth/microbiology* ; Host-Pathogen Interactions ; Epithelial Cells/microbiology* ; Cells, Cultured ; Porphyromonas gingivalis