Yu Li

An ABL-loaded micro/nanoparticle hybrid hydrogel integrates localized, heat-triggered drug release with mild photothermal therapy to promote neovascularization and bone regeneration in critical-sized cranial defects.

Objective: The integration of temporary anchorage devices (TADs) to aid clear aligner therapy (CAT) represents an evolving strategy that has gained expanding application over the past decade. This retrospective cohort study aimed to investigate the treatment outcomes of CAT cases involving maxillary incisor retraction following premolar extraction, managed with assistance of various TAD patterns. Subjects and methods: Adult premolar extraction CAT cases were included in this retrospective cohort study. The maxillary central incisors (U1) were grouped based on the TAD pattern for their retraction: Non-TAD (n = 54), posterior TADs only (P-TADs; n = 50), or combined anterior and posterior TADs (AP-TADs; n = 46). Pretreatment and post-treatment CBCTs quantified U1 lingualization, intrusion, retroclination and potential side effects such as apical root resorption (ARR), pulp chamber reduction and palatal dehiscence incidence. Results: P-TADs and AP-TADs patterns achieved greater U1 lingualization than the Non-TAD group. Vertical control differed markedly: AP-TADs achieved U1 intrusion (1.07 ± 1.64 mm), whereas P-TADs and Non-TAD showed U1 extrusion (−0.46 ± 1.12 mm and −1.51 ± 1.29 mm, respectively). U1 retroclination was over 10° in all three groups. AP-TADs exhibited greater ARR (1.31 ± 0.91 mm) and a higher proportion of Grade III ARR than the other groups. In regression analysis, the intrusion achieved was the strongest independent predictor of ARR. Pulp chamber reduction and palatal dehiscence incidence was similar among groups. Limitations: Residual confounding may persist due to the inherent limitations of retrospective study designs. Conclusions: In CAT cases involving maxillary incisor retraction following premolar extraction, P-TADs and AP-TADs patterns were associated with notable clinical treatment outcomes. These preliminary findings may provide prognostic indication for the management of such cases in the future.

Alveolar bone regions with low innate thickness are prone to dehiscence, potentially causing harmful gingival recession. In situ alveolar bone thickening via local bioagent administration has recently emerged as a promising research area. Parathyroid hormone-related protein (PTHrP), encoded by the Pthlh gene, plays a pivotal role in skeletal development and bone remodeling. In this study, we developed a recombinant adeno-associated virus (rAAV) vector overexpressing Pthlh (rAAV9- Pthlh ). Using a split-mouth design, we administered rAAV9- Pthlh via a single submucosal injection into the right maxillary buccal gingiva of rats. Micro-computed tomography scans, both in vivo and ex vivo, revealed a significant increase in alveolar bone thickness on the PTHLH sides 6 wk post-transfection. This enhanced alveolar bone formation was accompanied by marked periosteal thickening, with elevated expression of PTHrP, parathyroid hormone 1 receptor (PTH1R), OCN, and COL1A1. RNA sequencing of the buccal bone tissue showed upregulation of osteogenesis-related pathways along with increased mitophagy activity. Immunofluorescence confirmed enhanced colocalization of mitochondrial and lysosomal markers in the PTHLH group, primarily in the periosteum. Overexpressing Pthlh in primary rat periosteal stem cells via lentiviral transduction promoted cell proliferation and migration and elevated expression of COL1A1, as well as mitophagy markers BNIP3 and LC3-II. These effects were mitigated by Mdivi-1, an inhibitor of mitochondrial fission, suggesting potential involvement of mitophagy-dependent mitochondrial homeostasis maintenance. Finally, we established a rat model of repeated maxillary expansion and validated the effects of prophylactic rAAV9- Pthlh injection to protect against alveolar crest loss in this scenario. In conclusion, local rAAV9- Pthlh injection enhances in situ alveolar bone formation, holding potential for preventing dehiscence in aging or following orthodontic interventions. Additionally, overexpression of PTHrP in the alveolar periosteum has reiterated its well-documented role in expanding the pool of chondroskeletal progenitors, a process vital for the development of long bones and the mandibular condyle.

Maxillofacial bone defects pose significant clinical challenges due to unresolved inflammation, mechanical instability, and insufficient vascular integration. To address these limitations, we designed a multifunctional Ca/SrP microflower-doped triple-network hydrogel (MFs@PPB) engineered with polyethylene glycol diacrylate (PEGDA), poly(vinyl alcohol) (PVA), and borax to create a hydrogel with superior mechanical strength, self-healing properties, and adhesive interfaces. The triple-network structure enables dynamic self-healing under mechanical stress, while its bioactive ionic release, particularly strontium (Sr²⁺), modulates macrophage polarization, suppressing pro-inflammatory M1 macrophages and promoting pro-regenerative M2 polarization. This coordinated immunomodulation fosters angiogenesis and osteogenesis. The hydrogel's unique composition allows precise conformance to irregular mandibular defects, ensuring stable scaffold integration. In vivo, MFs@PPB effectively initiates immunomodulation to suppress chronic inflammation, followed by functional vascular network formation and biomimetic bone deposition, outperforming conventional strategies in structural and functional restoration. This study introduces a biomaterial strategy that bridges immune reprogramming with bioactive material properties, offering a transformative solution for mandibular reconstruction by overcoming the inflammation-regeneration paradox. The harmonized integration of immune modulation, angiogenic activation, and osteoinductive signaling within a single platform has broad implications for regenerative medicine.

Background: This study sought to thoroughly assess the skeletal impacts of Class II elastics therapy on the developing mandible, highlighting three‐dimensional changes in its functional units. Methods: Treatment records of 140 CBCT scans from 70 adolescent patients were retrospectively collected and assigned to one of two groups: the Class II elastics group ( n = 35), in which class II elastics were performed on the stainless steel archwires for more than 12 months, and the control group ( n = 35). Pre‐ and post‐treatment cone beam computed tomography (CBCT) images were used to assess changes related to the skeletal facial pattern, functional units, and transverse parameters. An independent t ‐test was used to compare between the two groups. Results: In the Class II elastics group, the mandibular body unit length (IAF‐MF) increased by 3.09 ± 3.16 mm from pre‐ to post‐treatment, significantly larger than that in the control group (1.37 ± 3.14 mm). No other mandibular functional unit or transverse parameters demonstrated significant differences between the two groups. Conclusions: Based on the single‐center sample included in this study, the adolescent group receiving prolonged Class II elastics may have exhibited a greater increase in mandibular body unit length compared to the group with minimal elastic use. However, these findings cannot be generalized without further validation.

Objective: A 26-year-old woman came for orthodontic treatment to improve her profile with protrusive lips. Diagnosed as bimaxillary protrusion, extraction followed by anterior retraction was indispensable for the case. However, her left upper lateral incisor was absent, the left upper canine had moved mesially and replaced the adjacent incisor, and the original canine location was restored with a long implant, which was in good condition. Surgical removal of the implant would be tricky and might lead to atrophy of the alveolar bone. In addition, the upper left central incisor had a short, curved root, which could not undergo significant movement. Materials and Methods: After crucial discussion between orthodontists and implantologists, based on digital setup, an innovative treatment plan was developed. Four incisors were extracted followed by clear aligner therapy for anterior retraction. An individualized zirconia abutment was installed on the upper left implant in a retroclined direction, cemented with a zirconia crown to replace the upper lateral incisor. Minimally invasive veneers were made to reshape the other upper incisors for better esthetics. Results: Finally, the patient had her profile greatly improved and the teeth well aligned without removal of the implant. Conclusion: Thus, the seemingly mission impossible was accomplished with a satisfactory outcome, thanks to imaginative treatment planning and delicate interdisciplinary collaboration based on digital simulation.

Temporomandibular joint osteoarthritis (TMJOA) is a progressive and debilitating degenerative joint disorder characterized by cartilage degradation. Its pathogenesis remains poorly understood, and current treatment strategies are insufficient to restore normal joint structure. Lipid metabolism disorders in condylar chondrocytes have been identified as key contributors to TMJOA development, with peroxisomes playing an essential regulatory role in this metabolic process. Although previous studies have suggested a role for peroxisomes in chondrocyte biology, their specific involvement in TMJOA pathogenesis remains unclear. This study is the first to demonstrate the involvement of peroxisomes in TMJOA and to elucidate the associated molecular mechanisms. A TMJOA mouse model was established via unilateral anterior crossbite surgery, revealing abnormal peroxisome quantity and function. In vitro experiments demonstrated that inhibiting peroxisome function alleviated mechanical stress-induced OA-like damage to chondrocytes. In Acan -CreER ^T2 Pex2 ^f/f conditional knockout (KO) mice, Pex2 KO inhibited peroxisome function and significantly attenuated TMJOA pathology. Mechanistically, peroxisome functional inhibition led to decreased levels of palmitic acid (PA), whereas exogenous PA exposure induced an OA-like phenotype in chondrocytes. Further investigation revealed that PA activated the WNT/PCP pathway by activating the JNK/c-JUN signaling axis. Multiomics analysis revealed S100a4 as a key downstream effector gene, and further CUT&RUN quantitative polymerase chain reaction and dual-luciferase reporter assays confirmed that c-JUN directly bound to the S100a4 promoter region (−101 to −94 bp) to regulate its transcription. Knockdown of S100a4 expression significantly reduced PA-induced Mmp13 expression in chondrocytes. In vivo experiments confirmed that intra-articular injection of PA upregulated S100a4 levels and promoted TMJOA development. In conclusion, this study is the first to elucidate the critical role of the peroxisome/PA/JNK/c-JUN/ S100a4 axis in cartilage degradation in TMJOA, providing a novel and promising therapeutic target for TMJOA.

Background: This study aimed to screen favorable and unfavorable profile outcomes in orthodontic camouflage treatment of skeletal Class II cases, based on which to identify the reference line and the associated value for the optimal incisor position objective (IPO) in such cases. Methods: A total of 140 Chinese adult skeletal Class II cases were included, who finished orthodontic camouflage treatment with anterior retraction following premolars extraction. Post-treatment lateral cephalograms were trimmed and converted into silhouettes, rated by a panel of orthodontists. The top 30% and bottom 30% ranked cases were included as the favorable and unfavorable profile group respectively. The distances of U1 anterior to the GALL line (U1-GALL), point A vertical (U1-Av), and ANS-Pog line (U1-ANPo) were measured as IPO indicators. Results: U1-ANPo in the favorable profile group was 4.74 ± 1.65 mm, significantly different from that in the unfavorable profile group (6.02 ± 3.61 mm). U1-GALL was −2.68 ± 2.30 mm and −1.12 ± 2.02 mm, and U1-Av was 4.49 ± 3.97 mm and 6.22 ± 4.42 mm, in the favorable and unfavorable profile group respectively, neither showing significant difference. Among three indicators, only U1-ANPo had a significant discriminatory capacity (AUC = 0.74, P = 0.007) for differentiating between the favorable and unfavorable profile group. Conclusions: In skeletal Class II orthodontic camouflage treatment, the relatively favorable post-treatment profiles are associated with the U1 position anterior to the ANS-Pog line. U1-ANPo of around 4.7 mm could be tentatively proposed as a practical IPO reference in treatment planning for such cases.

Three-dimensional (3D) facial images of autonomous maximal smile (AMS) hold unique value for generating orthodontic virtual patients. This study aimed to investigate upper lip elevation (ULE) in AMS using 3D facial images. A total of 212 Chinese participants with average dental and gingival display in AMS were enrolled and categorized into four groups: male adults (MAdu), female adults (FAdu), male adolescents (MA), and female adolescents (FA). Three-dimensional facial images were taken to measure upper lip length (ULL), philtrum length (PL), and upper vermilion height (UVH) at repose, and to measure upper lip length in AMS (ULL@AMS), ULE, and upper lip elevation ratio (ULER) in AMS. Cephalometric measurements were performed to assess maxillary incisor exposure (U1-Stms) and upper lip thickness (Sn-thickness, Ls-thickness, and Stms-thickness). Statistical analyses were conducted using analysis of variance and Pearson's chi-square tests. MAdu exhibited a significantly longer resting ULL (23.42 ± 2.23 mm) compared with FAdu (22.43 ± 1.83 mm), primarily due to their longer philtrum. ULL@AMS was 18.27 ± 2.20 mm in MAdu and 16.85 ± 2.36 mm in FAdu (P < 0.05); ULE was 5.15 ± 2.26 mm in MAdu and 5.58 ± 1.90 mm in FAdu (P > 0.05); ULER was 0.22 ± 0.09 in MAdu and 0.25 ± 0.08 in FAdu (P < 0.05). Both ULE and ULER were positively correlated with resting ULL and negatively correlated with Ls-thickness. ULL, ULL@AMS and ULE in AMS were precisely measured using 3D imaging across different sex and age groups, offering preliminary normative references for related orthodontic treatment and esthetic procedures.

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1–34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.