Horizontal alveolar bone resorption is common following tooth loss in the posterior mandible. Selecting an appropriate bone augmentation strategy is key to ensuring the long-term success of implant restoration. This article innovatively proposes a defect morphology-based classification system, categorizing bone defects into potential, favorable, partially favorable, and unfavorable types by analyzing the spatial relationship between the implant position and the outer alveolar ridge contour of adjacent teeth. This classification helps assess the spatial maintenance capacity of the defect site. Based on this classification, the article systematically outlines the corresponding implant timing and augmentation technique selection for different defect categories, establishing a clear clinical decision-making pathway to provide a reference for the implant restoration workflow in the posterior mandible.

Insufficient skeletal repair is the primary threat of health span and lifespan in elders with increasingly vast global burden; yet, to date, the knowledge of resolving this crisis remains limited. In this study, we addressed the specific mechanisms underlying aging-associated poor bone repair, which are driven by the mitochondrial DNA structures mitochondrial G-quadruplex (mtG4). We found that mtG4 is spatiotemporal-wisely accumulated within Pdgfra+ periosteal mesenchymal stromal/stem cells (PPM) both in healthy and premature aging, which substantially increases cellular senescence and the degenerative alterations of PPM. By utilizing transgenic lineage tracking, PPM organoids formation, mitochondrial transgenic mutation, organoids transplantation, and serial cellular molecular investigations, we reveal that mtG4 in PPM restricts vital mitochondrial genes’ transcription to cause mitochondrial dysfunction, which utterly leads to severe mitophagy and cell senescence. These senescent PPM demonstrates impaired stemness and disrupted fate determination, finally phenocopying aging-associated poor bone repair. This study decodes the mitochondrial genomic reasons for insufficient bone repair during aging, which offers insights for developing cell-type- and disease-specific senolytic therapies in the future.

OBJECTIVES:To introduce a universal scan calibrator (SC) and to evaluate its accuracy in the calibrated intraoral scan protocol (CISP) by comparison with two previously published SCs. MATERIALS AND METHODS:Three SCs were evaluated on an edentulous implant model containing six scan bodies (SBs) positioned at the screw-retained abutment (SRA) level: (1) a universal SC with a C-shaped window (SC-CW), (2) an SC covering only the alveolar ridge (SC-R), and (3) an SC limited to the palatal region (SC-P). Each SC was attached to the model and scanned 10 times using an intraoral scanner (IOS). The intraoral scans were subsequently corrected using the corresponding desktop scans of the SCs as reference data. A desktop scan of the model served as the reference. The test scans were superimposed onto the reference scan by: (1) using all SBs to evaluate the overall fit, and (2) using the first and second SBs to simulate the virtual Sheffield test. Linear and angular deviations of SRAs were measured using Python scripts. RESULTS:When aligned by all SBs, all three groups exhibited significant improvements in trueness and linear precision following correction. In the virtual Sheffield test, no statistically significant differences were observed in post-correction trueness or angular precision at the ending SRA6. All three groups achieved clinically acceptable trueness and precision values following correction. CONCLUSIONS:All three SCs yielded clinically acceptable impressions after correction under in vitro conditions. The novel SC represents a promising approach for CISP; however, further in vivo clinical evidence is required.

Conventional planar hydrogels cannot adequately conform to the irregular topography of complex wounds, which limits the efficiency of drug delivery. In this study, a morphologically adaptive microconical hydrogel (G/P@Cur MC) was developed, composed of physically cross-linked gelatin/polyvinyl alcohol and curcumin. Fabricated using a wound-replicating microporous mold, this dressing achieves conformal contact with the tissue and eliminates spatial blind zones in drug delivery. The G/P@Cur hydrogel integrates excellent mechanical properties, biocompatibility, and sustained release characteristics, and exhibits multiple biological activities, including the promotion of cell migration, angiogenesis, reactive oxygen species scavenging, and M2 macrophage polarization. In a full-thickness skin defect model in diabetic rats, the G/P@Cur MC significantly accelerated wound healing through synergistic antioxidant, anti-inflammatory, and pro-angiogenic mechanisms. This topology-adaptive platform offers a novel strategy for precision treatment of wounds.

ABSTRACT N6‐methyladenosine (m6A) is the most abundant internal chemical modification of eukaryotic RNA and a central mechanism of epitranscriptomic gene regulation. Although m6A was first characterized in messenger RNA (mRNA), it is also deposited on ribosomal RNA (rRNA), circular RNA, and other RNA species, where it regulates RNA stability, decay, splicing, nuclear export, translational efficiency, and ribosome function. m6A‐mediated gene regulation has attracted increasing attention as a mechanism that contributes to development, differentiation, metabolism, and disease. Its relevance is also becoming evident in skeletal biology and bone metabolism. METTL3‐mediated m6A modification of mRNA regulates the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells and contributes to the maintenance of bone mass, while METTL5‐mediated m6A modification of 18S rRNA supports bone formation through OSER1‐dependent antioxidant regulation. m6A modification has also been implicated in osteoclast differentiation and bone‐resorbing activity, acting through mRNA decay, nuclear export, and transcription factor regulation. In this review, we summarize the basic concepts of m6A modification and discuss its emerging roles in the regulation of bone metabolism, with particular focus on osteoblasts, osteoclasts, osteocytes, and bone marrow mesenchymal stem cells. We also consider the implications of m6A‐mediated epitranscriptomic regulation for oral and skeletal biology.

Craniofacial bone regeneration remains a major clinical challenge, yet the identity of orofacial mesenchymal stem/stromal cells (OMSCs) has not been fully elucidated. Here, we performed single-cell RNA sequencing (scRNA-seq) on mouse orofacial bone and identified multiple stromal cell clusters. Cell-cell communication mapping and trajectory inference uncovered the heterogeneity of OMSCs and functional divergence among subpopulations. We identified a previously unrecognized population, Smmhc-expressing mesenchymal stem/stromal cells (MSCs), at the earliest stage of the progenitor lineage trajectory. In vivo lineage tracing demonstrated that Smmhc+ MSCs are multipotent, giving rise to osteoblasts, osteocytes, periodontal ligament (PDL) cells, and dental pulp cells. Targeted ablation of Smmhc+ MSCs using SmmhcCreER;iDTR mouse model led to impaired orofacial bone development and disrupted orofacial tissue homeostasis, characterized by reduced osteogenic differentiation and non-cell autonomous reduction of bone resorption. Collectively, this study establishes a cellular atlas of OMSCs and identifies Smmhc+ MSCs as a functionally indispensable subset for craniofacial bone homeostasis, orchestrating the dynamic balance between osteogenesis and bone resorption within the orofacial skeletal niche.

N 6 -methyladenosine (m 6 A) RNA modification regulates diverse biological process. The m 6 A writers and downstream readers collaboratively undertake m 6 A-mediated RNA metabolism, yet the functional specificity among different writers and readers remains poorly understood. Using limb organogenesis as a development model, we uncover a critical and specific functional axis between the m 6 A reader YTHDC1 and writer METTL16. Depletion of either YTHDC1 or METTL16-but not METTL3-causes severe limb malformations, revealing unexpected functional selectivity. Mechanistically, we demonstrate that YTHDC1 specifically recognizes METTL16-deposited m 6 A marks on chromatin-associated RNAs, orchestrating cotranscriptional splicing of genes vital for cell cycle progression and DNA repair. Loss of YTHDC1 triggers genome-wide transcription arrest and dysregulates key developmental gene expression programs. Importantly, chromatin-bound YTHDC1 recruits splicing factors to transcriptional complex through liquid–liquid phase separation (LLPS), with alkalic arginine residues in its C-terminal region being molecular determinants. Our findings identified a selective and specific METTL16-m 6 A-YTHDC1 axis that couples RNA modification with cotranscriptional splicing during mammalian organogenesis, providing molecular insights into how epitranscriptomic regulation governs developmental decisions.

A dequate keratinized mucosa thickness is essential for the long-term health and esthetics of the peri-implant area. All along, for patients with soft tissue defects, FGG is the most commonly used treatment method. Although it can achieve better therapeutic effects, it also causes significant secondary injury areas. Objective : To achieve minimally invasive soft tissue augmentation without sutures, using tent pins to fix the soft tissue and ensure more reliable tissue stabilization. Materials and methods : This article describes a novel soft tissue augmentation technique that replaces conventional FGG with a combination of bone trephine and tack fixation. Results : All patients with this technique showed an improvement in their keratinized mucosal thickness in 1 month. No complications were observed, and all cases achieved tension-free healing and aesthetic outcomes. Conclusion : Pin technique has emerged as a reliable and predictable minimally invasive treatment approach for addressing insufficient peri-implant keratinized gingiva.

ABSTRACT The periosteal pouch technique is a promising alternative to conventional guided bone regeneration, but bilayer flap preparations on the buccal side are technique-sensitive and limit its clinical application. This study aimed to evaluate a simplified periosteal pouch technique designed to overcome these specific limitations through a modified flap design and a membrane-free crestal barrier. This retrospective study included 30 implants in 26 patients who received this simplified periosteal pouch technique for simultaneous horizontal bone augmentation in posterior mandibular single-tooth sites. The 6-month implant survival rate was 100%. The mean horizontal bone gain at the implant platform was 3.24 ± 1.70 mm. Sites with more severe initial deficiencies (buccal bone width < 0.5 mm) demonstrated significantly greater gains (4.26 ± 1.65 mm). The proposed simplified technique achieves reliable horizontal bone gain and favorable clinical bone quality. By addressing key limitations of the classic pouch technique, this approach offers a predictable and simplified solution for augmenting the posterior mandible.

Bone repair is a complex regenerative process involving inflammatory responses, vascular remodeling, and stem cell-mediated osteogenesis, wherein the immune microenvironment plays a critical regulatory role. Neutrophils have long been recognized as short-lived, pro-inflammatory effector cells primarily responsible for pathogen clearance and tissue debridement, and may even trigger inflammatory tissue damage when abnormally activated. Their regenerative potential in bone healing has, therefore, been significantly underestimated. Emerging evidence suggests that neutrophils are pivotal contributors to the bone repair process, exhibiting remarkable functional diversity that extends beyond their classical inflammatory roles. During the repair process, neutrophils assist in extracellular matrix (ECM) deposition and secrete pro-angiogenic factors, thereby fostering the early repair microenvironment. Meanwhile, they modulate the immune microenvironment through bidirectional interactions with macrophages and other immune cells, and promote bone regeneration by facilitating the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs). Recent studies have also begun to elucidate the temporal dynamics and circadian regulation of neutrophil functions during tissue repair. Conversely, under pathological conditions, aberrantly activated neutrophils can disrupt these finely tuned processes and drive pathological bone repair. Collectively, these findings necessitate a redefinition of the role of neutrophils in bone repair and underscore the importance of exploring new concepts and directions in neutrophil biology.

Wound healing is a highly dynamic and metabolically demanding process. However, the primary drivers of metabolic alterations involved in this process remain incompletely understood. Here, we employed multiomics profiling of clinical samples to investigate metabolic alterations during wound healing. Our analyses revealed significant activation of the TCA cycle and identified α-ketoglutarate (αKG) as a central regulator orchestrating the reparative phase. Systemic administration of αKG promoted wound closure and re-epithelialization, characterized by enhanced neo-tissue formation with an extended epithelial tongue. Mechanistically, αKG promoted cell proliferation via the cell cycle pathway and enhanced fibroblast-derived TGF-β signaling to induce epithelial-mesenchymal transition-like programs in epithelial cells. To address the spatial metabolic heterogeneity, we developed a transdermal MN platform based on gelatin methacryloyl for localized αKG delivery, further accelerating tissue repair. Collectively, these findings identify αKG as a metabolic driver of wound repair, reveal its dual role in modulating the epithelial-fibroblast microenvironment, and introduce a targeted bioengineering strategy with translational potential for both acute and chronic wound management.

OBJECTIVES:To identify the predictors, develop and validate a nomogram for implant buccal shoulder dehiscence following horizontal bone augmentation using the full-thickness envelope flap technique (FEFT). MATERIAL AND METHODS:A total of 318 implants in 250 patients receiving FEFT were included in the study. Implants were classified as "buccal shoulder dehiscence" or "buccal shoulder coverage" based on radiographic images obtained at 6 months postoperatively. Predictive factors for buccal shoulder dehiscence were evaluated using regression analysis. A nomogram was constructed, and model performance was assessed through calibration and discrimination analyses. RESULTS:Six factors were identified as predictors: initial deficit depth, graft overhanging angle, bone graft contour relative to the bone arch, type of bone substitute material, implant bucco-lingual position with respect to the initial alveolar bone profile, and implant site. The model showed an apparent area under the curve (AUC) of 0.899. This performance remained robust after patient-level cluster bootstrap validation (mean AUC = 0.886). The model demonstrated acceptable calibration, and decision curve analysis confirmed net clinical benefit. CONCLUSIONS:This nomogram provides a practical tool for predicting buccal shoulder coverage at 6 months after implant placement with simultaneous FEFT. TRIAL REGISTRATION:Trial Registration: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR2500115545).

Skeletal development, maintenance, and repair require precise control of protein production, yet mRNA levels often correlate poorly with protein abundance. Translation is the process through which mRNA is converted into protein, but its role in skeletal biology remains much less understood than that of transcriptional regulation. Recent advances in translatomics have begun to reveal how translational regulation contributes to skeletal development, homeostasis, and repair. Here, we summarize translational control across skeletal lineages, developmental stages, and disease settings. We also discuss emerging approaches for studying mRNA translation and potential therapeutic opportunities that target translational pathways. Understanding how translational regulation shapes skeletal health and disease will open new avenues for precise interventions for skeletal defects.

OBJECTIVE:To evaluate the effect of four scan calibrator (SC) morphologies on the accuracy of calibrated complete-arch implant intraoral scans. METHODS:A study model featuring six scan bodies (SBs) at the screw-retained abutment (SRA) level was fabricated, and reference data were obtained by scanning the model with an industrial scanner. A universal SC was manufactured in four morphologies: (1) tubular (SC-TU), (2) crumpled (SC-CR), (3) spherical (SC-SP), and (4) polyhedral (SC-PO). Each SC was attached to the model, and the resulting model-SC assembly was scanned ten times (n = 10) using an intraoral scanner (IOS) to obtain uncalibrated scans. These uncalibrated datasets were then calibrated using the corresponding desktop scans of the SCs. Both the uncalibrated and calibrated scans were registered against the reference scan via two alignment strategies: (1) using all SBs to assess the overall fit, and (2) using only the first and second SBs to simulate the Sheffield test. Linear deviations between the central points of SRAs were calculated using a custom Python script. RESULTS:When aligned using all SBs, trueness was comparable among the four SC-assisted groups, whereas the SC-CR group exhibited significantly lower post-calibration precision (40.11 ± 35.21 μm) than the SC-SP (29.63 ± 17.37 μm) and SC-PO (28.08 ± 13.48 μm) groups. In the virtual Sheffield test, the SC-SP (86.30 ± 34.25 µm) group demonstrated significantly higher trueness than the SC-CR group (162.06 ± 62.45 µm) following calibration at the distal SRA6. Furthermore, the SC-PO (66.21 ± 29.96 μm) group exhibited significantly higher post-calibration precision than the other three SC groups at SRA6. CONCLUSIONS:SC morphologies influence the accuracy of calibrated complete-arch implant intraoral scans. SC-PO demonstrated the highest post-calibration precision. CLINICAL SIGNIFICANCE:The proposed SC morphologies, except for SC-CR, may help correct IOS stitching errors. The polyhedral morphology may represent a favorable design choice for SC fabrication.

Most synthetic implants trigger a foreign-body reaction that envelops the device in a dense fibrotic capsule, blocking close tissue integration. By contrast, titanium establishes direct bone-implant contact and long-term clinical function. Exactly how the initial immune cues at the titanium interface redirect inflammation toward rapid resolution and pro-regenerative pathways, thereby maximizing implant tissue integration and functional performance, remains to be fully elucidated. Here, we profile the early immune microenvironment around titanium implants and find neutrophils to dominate the cellular dynamics using single cell RNA sequencing in a large animal model. Neutrophils are recruited sooner and cleared faster than in standard tissue healing process, and their depletion in mice markedly impairs integration. Titanium implants activate neutrophil NF-κB signaling, provoking chemokine release that attracts mesenchymal stem cells (MSCs) while simultaneously inducing neutrophil apoptosis; extracellular vesicles (EVs) from these apoptotic cells further enhance MSC osteogenesis. These findings offer valuable insights into biomaterial-tissue interactions and provide a foundation for optimizing implant design and clinical outcomes.

This in vitro study aimed to evaluate the impact of a novel Tooth-Shaped Auxiliary Device (TSAD) on the scanning accuracy (trueness and precision) of complete-arch implant impressions, in comparison to conventional splinted impressions (CI) and standard intraoral scans (IOS). A mandibular edentulous master model with six implants was used as the reference. Three impression methods were tested (n = 10 per group): CI, IOS, and IOS with the TSAD. The TSAD, featuring a biomimetic occlusal geometry, was digitally designed and 3D-printed to attach to scan bodies. Scans were performed using a 3Shape TRIOS 3 scanner across three implant configurations (BCDE, BCDEF, and ABCDEF). The resulting Standard Tessellation Language (STL) files and the reference scan were used to calculate trueness and precision using best-fit alignment and mean linear deviation between implants. Statistical analysis was performed using two-way ANOVA with Bonferroni correction for post-hoc comparisons, and simple effects analyses for significant interactions. The effect of TSAD on scanning accuracy varied by implant configuration. In the BCDE and BCDEF configurations, no statistically significant differences in trueness or precision were observed between TSAD and CI (trueness: P = 1.000 and P = 0.883; precision: P = 0.662 and P = 0.368, respectively). In the ABCDEF configuration, TSAD demonstrated significantly better trueness and precision than both CI and IOS (all P < 0.001 for trueness; precision: P = 0.024 vs. CI, P = 0.003 vs. IOS). The precision of TSAD remained stable across the three implant configurations (P = 0.435), whereas the trueness and precision of IOS varied significantly across configurations (both P < 0.001). Under in vitro conditions, TSAD demonstrated accuracy similar to CI in partial-arch configurations and significantly better accuracy than both CI and IOS in the full-arch configuration. Further studies are needed to validate its performance under clinical conditions.

Bone regeneration in complex pathological environments (e.g., infection or diabetes) is particularly challenging. Traditional collagen barrier membranes often degrade quickly and lack multifunctional bioactivity, limiting their effectiveness under such conditions. Here, we describe a collagen-based Janus membrane for advanced guided bone regeneration in these challenging settings. The membrane features an asymmetric bilayer architecture: the soft-tissue side comprises a dense barrier layer formed by electrodeposition, whereas the bone-defect side consists of a porous repair layer. The repair layer incorporates copper-doped hydroxyapatite particles and PLGA microspheres loaded with the natural polyphenol proanthocyanidin, endowing the membrane with potent antibacterial, antioxidant, and osteoconductive properties. Copper ions released from the mineral phase stimulate angiogenic signaling and promote neovascularization, while proanthocyanidin stabilizes the collagen matrix and mitigates inflammation. Meanwhile, the electrodeposited barrier layer confers enhanced mechanical strength and structural integrity, effectively preventing soft-tissue infiltration and bacterial invasion. Moreover, the membrane modulates macrophage glucose metabolism and mitophagy, thereby reducing reactive oxygen species and promoting macrophage polarization toward the anti-inflammatory M2 phenotype, creating an osteoimmune environment conducive to new bone formation. In rat models of infected calvarial and diabetic periodontal defects, the membrane preserves its barrier protection and microenvironmental modulation capacity under pathological stress, leading to enhanced tissue regeneration. This collagen-based Janus membrane thus represents a promising strategy for guided bone regeneration in complex clinical scenarios such as infection or metabolic disorders.

ABSTRACT Oral mucosal lesions present significant therapeutic challenges due to the complex oral environment and the limitations of conventional biomaterials in clinical application. Herein, a self‐gelling supramolecular powder composed of polyethyleneimine (PEI), poly (acrylic acid) (PAA), and α‐lipoic acid (LA) is developed for oral ulcer management. Upon contact with saliva, the powder rapidly absorbs water and undergoes instantaneous self‐gelation (<5 s), forming a physically cross‐linked hydrogel that exhibits robust wet adhesion to oral mucosal tissues. The incorporation of LA enhances the mechanical integrity of the network without increasing swelling, while enabling sustained LA release that imparts intrinsic anti‐inflammatory bioactivity. In a murine oral ulcer model, the optimized PEI/PAA/1%LA formulation accelerates wound healing, reduces pain‐associated behaviors, and suppresses local expression of IL‐1β and TNF‐α. Mechanistically, transcriptomic analysis reveals that LA exerts its anti‐inflammatory effects through comprehensive suppression of both classical and noncanonical NF‐κB signaling pathways, downregulating Nfkb1, Nfkb2, and downstream inflammatory cytokines. By integrating durable wet adhesion with controlled therapeutic delivery, this supramolecular system offers a clinically translatable strategy for oral mucosal regeneration that addresses both biological healing requirements and patient comfort.

N6-methyladenosine (m6A) RNA modification regulates diverse biological process. The m6A writers and downstream readers collaboratively undertake m6A-mediated RNA metabolism, yet the functional specificity among different writers and readers remains poorly understood. Using limb organogenesis as a development model, we uncover a critical and specific functional axis between the m6A reader YTHDC1 and writer METTL16. Depletion of either YTHDC1 or METTL16-but not METTL3-causes severe limb malformations, revealing unexpected functional selectivity. Mechanistically, we demonstrate that YTHDC1 specifically recognizes METTL16-deposited m6A marks on chromatin-associated RNAs, orchestrating cotranscriptional splicing of genes vital for cell cycle progression and DNA repair. Loss of YTHDC1 triggers genome-wide transcription arrest and dysregulates key developmental gene expression programs. Importantly, chromatin-bound YTHDC1 recruits splicing factors to transcriptional complex through liquid-liquid phase separation (LLPS), with alkalic arginine residues in its C-terminal region being molecular determinants. Our findings identified a selective and specific METTL16-m6A-YTHDC1 axis that couples RNA modification with cotranscriptional splicing during mammalian organogenesis, providing molecular insights into how epitranscriptomic regulation governs developmental decisions.

Peri-implantitis (PI) is a multifactorial chronic inflammatory disease characterized by persistent mucosal inflammation and progressive marginal bone loss, yet the tissue architecture and cellular programs that sustain chronic inflammation remain incompletely defined. Here, we integrate single-cell and spatial transcriptomic analyses with targeted validation to map the PI microenvironment and its regulatory circuits. PI lesions exhibit marked immune enrichment, including expansion of CXCR4⁺ aged neutrophils with enhanced survival signaling consistent with apoptosis delay. Spatial and communication analyses reveal a PI-specific stromal–myeloid organization in which fibroblast-rich regions are closely associated with myeloid hotspots and display heightened CXCL- and CSF-related signaling. Within the fibroblast compartment, inflammatory myofibroblasts emerge as a prominent predicted source within a CXCL/CSF-enriched secretory program, with CXCL6 and CSF3 highlighted as candidate mediators of neutrophil recruitment and survival. Functionally, blockade of the CXCR2 axis reduces neutrophil infiltration and mitigates peri-implant bone resorption. Upstream regulatory analyses nominate STAT4 as a candidate upstream regulator of the inflammatory stromal program; pharmacologic perturbation with lisofylline reduces CXCL6/CSF3 expression, weakens neutrophil chemotaxis, partially restores apoptosis sensitivity, and alleviates inflammation and bone loss in vivo. Together, these findings support a stromal–neutrophil circuit that sustains chronic inflammation in PI and highlight stromal inflammatory programs and neutrophil recruitment/survival pathways as potential therapeutic entry points.