Shujiao Qian

Aim: Peri‐implant tissues are more susceptible than gingiva to rapid inflammatory breakdown, but the cellular basis of this vulnerability remains unclear. This study investigated (1) whether clinically healthy peri‐implant mucosa already displays an immune landscape distinct from healthy gingiva, and (2) which cellular states and molecular pathways characterize the transition from peri‐implant health to peri‐implantitis. Methods: An integrative single‐cell RNA‐sequencing analysis was performed using clinically healthy pre‐loading peri‐implant mucosa ( n = 3), healthy gingiva ( n = 17), and peri‐implantitis tissues ( n = 3). Healthy peri‐implant mucosa was first compared with a healthy gingival reference atlas to define the baseline peri‐implant immune niche. Disease‐associated changes were then examined by comparing healthy peri‐implant and peri‐implantitis tissues. Key findings were validated in independent tissue cohorts comprising healthy gingiva, clinically healthy peri‐implant mucosa, and peri‐implantitis ( n = 6 participants per group) using multiplex immunofluorescence, immunohistochemistry, and reactive oxygen species (ROS) detection. Results: Clinically healthy peri‐implant mucosa showed greater immune‐cell enrichment than healthy gingiva, most notably within the myeloid compartment. Among myeloid cells, a CXCR2 ⁺ neutrophil subset exhibited the highest baseline signature for neutrophil extracellular trap (NET) formation, indicating an immune‐enriched state with enhanced NET‐associated transcriptional potential, despite clinical health. In peri‐implantitis, this CXCR2 ⁺ neutrophil subset expanded further and displayed increased oxidative, chemotactic, and NET‐associated programs, supported by tissue validation of MPO, CXCR2, CitH3, and ROS signals. Cell–cell communication analysis nominated fibroblast‐derived CXCL signaling as a potential contributor to CXCR2 ⁺ neutrophil recruitment. NSUN6, an RNA modification enzyme, was enriched in disease‐associated CXCR2 ⁺ neutrophils, and NSUN6 knockdown in neutrophil‐like cells attenuated CXCR2 ⁺ cell enrichment and NET‐associated marker expression. Conclusion: Clinically healthy peri‐implant mucosa before functional loading is not immunologically equivalent to gingiva, but represents an immune‐primed niche that may lower the threshold for inflammatory breakdown. These findings may not be directly generalized to long‐term functionally loaded implants. Peri‐implantitis is characterized by amplification of an oxidative CXCR2 ⁺ neutrophil state, with fibroblast‐derived CXCL–CXCR2 signaling and NSUN6‐associated neutrophil activation emerging as candidate pathways for future diagnostic and therapeutic investigation.

Peri‐implantitis (PI) is a common disease that occurs in most dental implant patients. The progressive bone resorption related to PI markedly affects patients’ life quality. Thermosensitive hydrogels composed of chitosan (CS) and β‐glycerophosphate (GP) have been previously employed for the PI treatment. However, their restricted mechanical strength undermined the bone‐repairing outcome. The formation of a hybrid network by adding inorganic crosslinking components may help improve the mechanical properties of hydrogels. Moreover, copper (Cu) ions have been confirmed to be beneficial for bacterial killing in a concentration‐dependent manner. Hence, a copper chelated thermosensitive hybrid hydrogel (Cu/CGT) is fabricated here by incorporating tetraethoxysilane into the Cu doped CS and GP solution. Material characterization, biocompatibility, and antibacterial tests are conducted in vitro and in vivo to determine the physical and biological properties of hydrogels. The result shows that 1Cu/CGT with improved compressive modulus can not only promote the osteogenic differentiation and suppress the inflammation, but also show notable bacterial killing ability against pathogenic bacteria. The ideal Cu release profile of 1Cu/CGT may contribute to the satisfactory biomedical performance of hydrogels. In summary, this study develops a thermosensitive hybrid hydrogel with ideal bacterial‐defensive and pro‐osteogenic performance, exhibiting good potential for clinical treatment of PI.

Local immunoinflammatory events instruct skeletal stem cells (SSCs) to repair/regenerate bone after injury, but mechanisms are incompletely understood. We hypothesized that specialized Tregs are necessary for bone repair and interact directly with SSCs through organ-specific messages. Both in human patients with bone fracture and a mouse model of bone injury, we identified a bone injury–responding Treg subpopulation with bone-repair capacity marked by CCR8. Local production of CCL1 induced a massive migration of CCR8 ⁺ Tregs from periphery to the injury site. Depending on secretion of progranulin (PGRN), a protein encoded by the granulin ( Grn ) gene, CCR8 ⁺ Tregs supported the accumulation and osteogenic differentiation of SSCs and thereby bone repair. Mechanistically, we revealed that CCL1 enhanced expression levels of basic leucine zipper ATF-like transcription factor (BATF) in CCR8 ⁺ Tregs, which bound to the Grn promoter and increased Grn translational output and then PGRN secretion. Together, our work provides a new perspective in osteoimmunology and highlights possible ways of manipulating Treg signaling to enhance bone repair and regeneration.

Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method. The incorporation of Ce-MBGNs remarkably improves surface hydrophilicity by increasing the surface areas. The bioactive ions are appropriately released, thereby promoting mesenchymal stem cell proliferation and differentiation under diabetic conditions. The conversion between Ce(III) and Ce(IV) endows Ce-MBGNs coating with antioxidative nanoenzymes properties to scavenge diabetes-induced ROS, resulting in macrophage polarization towards the anti-inflammatory phenotype. The therapeutic effect of Ce-MBGNs-modified titanium implants is also verified in diabetic rats by inhibiting inflammatory responses and accelerating early osseointegration. Taken together, the findings reveal that the ROS-scavenging and immunomodulation activity of the Ce-MBGNs coating contributes to enhanced osseointegration, and provides a novel implant surface for diabetic patients.

Aim: To examine the independent and joint associations of oral microbiome diversity and diet quality with risks of all‐cause and cause‐specific mortality.Materials and Methods: We included 7,055 eligible adults from the U.S. National Health and Nutrition Examination Survey (NHANES). Oral microbiome diversity was measured with α‐diversity, including the Simpson Index, observed amplicon sequence variants (ASVs), Faith's phylogenetic diversity, and Shannon–Weiner index. Dietary quality was assessed using the Healthy Eating Index‐2015 (HEI‐2015). Cox proportional hazard models were used to assess the corresponding associations.Results: During a mean follow‐up of 9.0 years, we documented 382 all‐cause deaths. We observed independent associations of oral microbiome diversity indices and dietary quality with all‐cause mortality (hazard ratio [HR] = 0.63; 95% confidence interval [CI]: 0.49–0.82 for observed ASVs; HR = 0.68, 95% CI: 0.52–0.89 for HEI‐2015). Jointly, participants with the highest tertiles of both oral microbiome diversity (in Simpson index) and HEI‐2015 had the lowest hazard of mortality (HR = 0.37, 95% CI: 0.23–0.60). In addition, higher oral microbiome diversity was associated with lower risks of deaths from cardiometabolic disease and cancer.Conclusions: Higher oral microbiome α‐diversity and diet quality were independently associated with lower risk of mortality.

Aim: Impairment of masticatory function in elderly patients with terminal dentition due to stage IV periodontitis (TDS4P) may lead to lower nutritional intake. The study aimed to report the dietary intake and nutrition status of elderly patients with TDS4P and compare them with those of the elderly Chinese population and the Chinese Dietary Reference Intakes (DRIs).Materials and Methods: Fifty‐one consecutive subjects (≥55 years old) with TDS4P were enrolled. Average dietary intake was evaluated based on a 3‐day 24‐h dietary recall (24HR) and food frequency questionnaire (FFQ). The daily intake of fresh vegetables and fruits, dietary energy as well as macro and micronutrients were calculated and compared with matched national data and the Chinese DRIs. Nutritional status was assessed by Short‐Form Mini‐Nutritional assessment.Results: Of the subjects, 19.6% (95% CI: 7.2%–28.1%) were at risk of malnutrition. The mean daily energy intake was 1517.4 kcal (95% CI: 1400.5–1634.3) for males and 1110.7 kcal (95% CI: 1001.5–1219.9) for females, which were very low compared with both the national data and the DRIs. Females derived a higher percentage of energy from fat. The mean daily intake of vegetables was 151.4 g (95% CI: 128.1–174.8) by FFQ and 130.9 g (95% CI: 104.6–157.3) by 24HR. Both results were significantly lower than the national reports (95% CI: 310.3–340.1) and the DRIs (300–450 g). Insufficient micronutrient intake, especially vitamins A, C and E, was also found.Conclusions: Elderly subjects with TDS4P had a lower daily energy intake, vegetable and fruit consumption and essential macro and micronutrient intake. More studies are needed to clarify the impact of periodontitis and tooth loss/replacement on nutrition and healthy ageing.

Aim: Emerging evidence points to a two‐way relationship between periodontitis and dietary choices and, thus, nutrition. This study aimed to assess the potential cause–effect relationship between the periodontitis stage, loss of functional tooth units (FTUs), masticatory function, and intake of different food groups using path analysis.Materials and Methods: A single calibrated examiner determined the periodontitis stage of a consecutive sample of 241 Chinese subjects reporting for tooth replacement. Their masticatory function was quantified by the mixing ability of a two‐colour chewing gum. Validated food frequency questionnaires were used to calculate the intake of 33 food group items by an experienced calibrated rater. After verification of assumptions, visual structural equation modeling was performed with Amos 23. The consistency of results and the potential modifying effect of age were assessed in 9043 subjects from the NHANES database.Results: Highly significant models were constructed using periodontitis stage and age as exogenous factors. Periodontitis stage diagnosis significantly affected the number of posterior FTUs and oral health‐related quality of life (OHRQoL, path coefficient [PC] = –0.55 and −0.20, p < .05, respectively). In the model, FTUs also had an independent effect on OHRQoL (PC = 0.23, p < .05). FTUs determined the level of masticatory function (PC = –0.38, p < .05), which in turn affected vegetable intake but not fruit or meat intake (PC = –0.18, p < .0.5, PC = 0.06, NS and PC = 0.11, NS, respectively). The effect of age was significant for vegetable and meat intake and was also correlated with periodontitis stage diagnosis. Analysis of the NHANES database confirmed the negative impact of periodontitis on the number of occluding pairs and vegetable consumption for the 18–44, 45–60 and >60 age groups.Conclusions: Periodontitis showed a potential cause–effect pathway affecting vegetable intake across cultures and age groups. The size of the effect is potentially of clinical and public health significance. Additional studies, including intervention trials, are required to test this potential mechanism linking oral health to nutrition.

Aim: To reveal the cellular composition and molecular environment of the periodontal and peri‐implant inflammatory infiltrates through a single‐cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri‐implant/periodontal tissue immunity.Materials and Methods: High‐throughput single‐cell transcriptomic profiling of peri‐implant tissues from patients with peri‐implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri‐implantitis and periodontitis.Results: Based on our single‐cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri‐implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation‐promoting fibroblasts as well as a predominance of CXCL8⁺ fibroblast–CXCR2⁺ neutrophil interaction in peri‐implantitis.Conclusions: Our study indicated that the predominance of CXCL8⁺ fibroblast–CXCR2⁺ neutrophil interaction might underline the enhanced host response in peri‐implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri‐implantitis.

Objectives: To evaluate the clinical, radiographic, and esthetic outcomes of immediate implant placement with buccal bone dehiscence in the anterior maxilla.Methods: In this case series, implants were inserted immediately after tooth extraction in sockets with buccal bone dehiscence. Guided bone regeneration (GBR) with a papilla preservation flap and simultaneous connective tissue grafting (CTG) was used. The following outcome variables were measured: mid‐facial mucosal recession, probing depth, bleeding on probing, Pink Esthetic Score (PES), marginal bone loss, and thickness of buccal bone plate (TBP).Results: 12 patients were recruited. Stable mid‐facial mucosal level (−0.03 ± 0.17 mm) and excellent soft‐tissue esthetic outcomes (PES, 9.17 ± 0.72) were achieved at 1 year. The TBP at platform level was 2.01 ± 0.31 mm at 1‐year follow up with a resorption rate of 28.90% ± 15.14%.Conclusions: Immediate implant placement using GBR performed with a papilla preservation approach and simultaneous CTG is a feasible treatment procedure in compromised extraction sockets in the anterior region. Favorable esthetic outcomes and buccal bone thickness were obtained. Further studies were needed to evaluate the long‐term tissue alteration.

Background: The aim of this study was to compare the 3‐year clinical outcomes of narrow‐diameter implants (NDI) with standard‐diameter implants (SDI) in conjunction with lateral bone augmentation in atrophic posterior jaws.Materials and Methods: Fifty patients were included and randomly assigned into two groups: Patients in Group 1 received NDI (Ø3.5 mm); patients in Group 2 received SDI (Ø4.3 mm) with simultaneous lateral bone augmentation. Implant survival rates, complications, crestal bone loss, peri‐implant conditions, treatment cost, and patient satisfaction were compared.Results: Three patients dropped out the follow‐up. No implant loss was observed. The difference in technical complication rates between the two groups was 3.8% (95% CI: −13.7% to 21.3%). No significant differences in crestal bone loss were found between two groups at 3‐year follow‐up (0.55 ± 0.76 vs 0.41 ± 0.41 mm, p = .429). A total of 20.8% (5/24) of NDI were diagnosed with mucositis and 8.3% (2/24) with peri‐implantitis. A total of 17.4% (4/23) of SDI showed mucositis and (1/23) 4.3% showed peri‐implantitis. The total cumulative cost of treatment per patient in Group 1 (2849.6 USD, 95% CI: 2726.8–2972.4) was significantly lower than that in Group 2 (3581.4 USD, 95% CI, 3460.9–3701.9) over the 3‐year follow‐up (p < .01). The patient satisfaction rating of operation was significantly higher in Group 1 (85.42 ± 7.41 vs 80.48 ± 7.95, p = .033).Discussion: NDI yielded favorable implant survival, acceptable technical and biological complications, and high patient satisfaction supporting single crowns in the atrophic posterior region after 3‐year follow‐up. NDI might be a reasonable alternative in horizontally deficient posterior jaws.Trial Registration: Clinicaltrials.gov identifier: ChiCTR1800020426.