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Although transcrestal sinus floor elevation (TSFE) is widely used for cases of insufficient residual bone height in the posterior maxilla, few studies have focused on the risk factors of early implant failure associated with TSFE procedures. This study aimed to identify and summarize the possible risk factors of implant failure associated with TSFE to ensure a more predictable implant survival rate using TSFE. We report the treatment of a patient with implant failure following TSFE and discuss this case's possible associated risk factors. A standard implant with a diameter of 4.8 mm and length of 10 mm was used after the TSFE procedure. Implant loosening was suddenly observed six weeks after the initial surgery. Factors that could result in early implant failure included patient-related risk factors, anatomical factors of the operational area, and operation- and implant-related factors. Within the current study's limitations, the graft material particles between the implant surface and socket could be considered a direct risk factor resulting in implant failure. Therefore, more attention should be paid to socket cleaning during the TSFE procedure, and loose particulate grafting materials should be discouraged. Another significant consideration for implant loss is the possibility of fractures in the buccal or palatal cortical plates during the site preparation and implant insertion. Thus, these factors should be studied further and receive more clinical attention.
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To effectively address underlying issues and enhance the healing process of hard-to-treat soft tissue defects, innovative therapeutic approaches are required. One promising strategy involves the incorporation of bioactive substances into biodegradable scaffolds to facilitate synergistic tissue regeneration, particularly in vascular regeneration. In this study, we introduce a composite hydrogel design that mimics the extracellular matrix by covalently combining gelatin and hyaluronic acid (HA), with the encapsulation of deferoxamine nanoparticles (DFO NPs) for potential tissue regeneration applications. Crosslinked hydrogels were fabricated by controlling the ratio of HA in the gelatin-based hydrogels, resulting in improved mechanical properties, enhanced degradation ability, and optimised porosity, compared with hydrogel formed by gelatin alone. The DFO NPs, synthesized using a double emulsion method with poly (D,L-lactide-co-glycolide acid), exhibited a sustained release of DFO over 12 d. Encapsulating the DFO NPs in the hydrogel enabled controlled release over 15 d. The DFO NPs, composite hydrogel, and the DFO NPs loaded hydrogel exhibited excellent cytocompatibility and promoted cell proliferationin vitro. Subcutaneous implantation of the composite hydrogel and the DFO NPs loaded hydrogel demonstrated biodegradability, tissue integration, and no obvious adverse effects, evidenced by histological analysis. Furthermore, the DFO NPs loaded composite hydrogel exhibited accelerated wound closure and promoted neovascularisation and granular formation when tested in an excisional skin wound model in mice. These findings highlight the potential of our composite hydrogel system for promoting the faster healing of diabetes-induced skin wounds and oral lesions through its ability to modulate tissue regeneration processes.
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Materiais Biomiméticos , Desferroxamina , Gelatina , Ácido Hialurônico , Hidrogéis , Nanopartículas , Gelatina/química , Desferroxamina/química , Desferroxamina/farmacologia , Animais , Hidrogéis/química , Ácido Hialurônico/química , Nanopartículas/química , Camundongos , Materiais Biomiméticos/química , Proliferação de Células/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Humanos , Porosidade , Regeneração , BiomiméticaRESUMO
BACKGROUND: Fgf9 mutation was found in cleft palate patients. Our previous study indicated that Fgf9 promotes timely elevation of palate by regulating hyaluronic acid (HA) accumulation at embryonic day 13.5 (E13.5). HA is synthesized by hyaluronic acid synthases (HAS) isoforms 1, 2, or 3. However, how FGF9 regulates HA in palatogenesis is still unclear. METHODS: Using Ddx4-Cre mice, we generated the Fgf9-/- mouse model (with exon 2 deletion). Immunohistochemistry was used to detect the location and expression of HAS2 in WT and the Fgf9-/- palate at E13.5. We also predicted the association between Fgf9 and Has2 within the developing palate by performing a bioinformatics analysis. The expression of ß-catenin, HAS2, and TCF7L2 were verified by Western blotting after knockout of Fgf9. Rescue experiments were performed by ELISA in vitro. RESULTS: Fgf9-/- mice exhibited 100% penetrance of the cleft palate. A knockout of Fgf9 confirmed that HAS2 and TCF7L2 expression was positively correlated with FGF9. TCF7L2 binds to the Has2 promoter, exhibiting the high specificity predicted by JASPAR. Additionally, increased HA expression by BML-284, TCF-dependent agonist, was blocked in Fgf9-/- palate because of the significant decline in TCF7L2 expression. CONCLUSIONS: FGF9 promotes HAS2 expression via Wnt/ß-catenin/TCF7L2 pathway with TCF7L2 activating transcription of Has2 in the palate.
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Fissura Palatina , beta Catenina , Camundongos , Animais , Fissura Palatina/genética , Ácido Hialurônico , Via de Sinalização Wnt , Fator 9 de Crescimento de Fibroblastos/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genéticaRESUMO
INTRODUCTION: The zygomaticomaxillary suture (ZMS) maturation evaluation is a reliable method for predicting the optimal timing of maxillary protraction. The objective of this study was to compare age distribution patterns of ZMS maturation stages between cleft lip and palate (CLP) patients and non-cleft lip and palate (non-CLP) patients to aid our comprehension in choosing the optimal timing of maxillary protraction. METHODS: Samples of 216 non-CLP and 220 CLP Asian patients without orthodontic and orthognathic treatment aged 5-25 years were scanned to evaluate the ZMS maturation stage by 2 evaluators blindly. Evaluators' agreements and bilateral ZMS maturation consistency were assessed by weighted kappa tests. Age distribution patterns of each ZMS maturation stage were described. Gender effect and age distribution differences between groups were analyzed using an independent t-test. RESULTS: Evaluators' agreements and bilateral ZMS maturation consistency were satisfying (weighted kappa coefficient >0.90). At stages A and B, patients with CLP were 1.3 and 0.4 years older than patients in the non-CLP group (P <0.001 and P = 0.01). In contrast, at stage C, patients with CLP were approximately 1.2 years younger (P = 0.004). Gender barely played a role in the divergence of ZMS maturation (P >0.05). No statistically significant difference was observed between ZMS maturation of patients with unilateral or bilateral cleft lip and palate (UBCLP) and patients with unilateral or bilateral cleft lip (UBCL) (P >0.05). CONCLUSIONS: The ZMS development of patients with CLP was premature at stage C, whereas delayed at stages A and B.
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Fenda Labial , Fissura Palatina , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Suturas Cranianas , Humanos , SuturasRESUMO
Cleft palate, a common global congenital malformation, occurs due to disturbances in palatal growth, elevation, contact, and fusion during palatogenesis. The Fibroblast growth factor 9 (FGF9) mutation has been discovered in humans with cleft lip and palate. Fgf9 is expressed in both the epithelium and mesenchyme, with temporospatial diversity during palatogenesis. However, the specific role of Fgf9 in palatogenesis has not been extensively discussed. Herein, we used Ddx4-Cre mice to generate an Fgf9-/- mouse model (with an Fgf9 exon 2 deletion) that exhibited a craniofacial syndrome involving a cleft palate and deficient mandibular size with 100% penetrance. A smaller palatal shelf size, delayed palatal elevation, and contact failure were investigated to be the intrinsic causes for cleft palate. Hyaluronic acid accumulation in the extracellular matrix (ECM) sharply decreased, while the cell density correspondingly increased in Fgf9-/- mice. Additionally, significant decreases in cell proliferation were discovered in not only the palatal epithelium and mesenchyme but also among cells in Meckel's cartilage and around the mandibular bone in Fgf9-/- mice. Serial sections of embryonic heads dissected at embryonic day 14.5 (E14.5) were subjected to craniofacial morphometric measurement. This highlighted the reduced oral volume owing to abnormal tongue size and descent, and insufficient mandibular size, which disturbed palatal elevation in Fgf9-/- mice. These results indicate that Fgf9 facilitates palatal growth and timely elevation by regulating cell proliferation and hyaluronic acid accumulation. Moreover, Fgf9 ensures that the palatal elevation process has adequate space by influencing tongue descent, tongue morphology, and mandibular growth.
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Fibroblast growth factor signaling is essential for mammalian bone morphogenesis and growth, involving membranous ossification and endochondral ossification. FGF9 has been shown to be an important regulator of endochondral ossification; however, its role in the early differentiation of chondrocytes remains unknown. Therefore, in this study, we aimed to determine the role of FGF9 in the early differentiation of chondrogenesis. We found an increase in FGF9 expression during proliferating chondrocyte hypertrophy in the mouse growth plate. Silencing of FGF9 promotes the growth of ATDC5 cells and promotes insulin-induced differentiation of ATDC5 chondrocytes, which is due to increased cartilage matrix formation and type II collagen (col2a1) and X (col10a1), Acan, Ihh, Mmp13 gene expression. Then, we evaluated the effects of AKT, GSK-3ß, and mTOR. Inhibition of FGF9 significantly inhibits phosphorylation of AKT and GSK-3ß, but does not affected the activation of mTOR. Furthermore, phosphorylation of inhibited AKT and GSK-3ß was compensated using the AKT activator SC79, and differentiation of ATDC5 cells was inhibited. In conclusion, our results indicate that FGF9 acts as an important regulator of early chondrogenesis partly through the AKT/GSK-3ß pathway.
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Diferenciação Celular/fisiologia , Condrócitos/metabolismo , Fator 9 de Crescimento de Fibroblastos/metabolismo , Animais , Desenvolvimento Ósseo , Cartilagem/metabolismo , Linhagem Celular , Proliferação de Células , Células Cultivadas , Condrogênese/fisiologia , Colágeno Tipo II/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Lâmina de Crescimento/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Macrophages are vital regulators of skeletal remodeling and osseous repair. Beta-tricalcium phosphate (ß-TCP) is a synthetic ceramic biomaterial that has shown promise as bone substitute. However, whether and how ß-TCP affects osteogenesis-related responses of macrophages has rarely been studied. The aims of this study were to explore (a) the effects of ß-TCP on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) co-cultured with macrophages and (b) on macrophage polarization as well as macrophage gene and protein expression profiles. BMSC osteogenic differentiation capacity in vitro was enhanced in ß-TCP-induced co-cultured BMSCs compared to that in BMSC monocultures. We also found that macrophages induced with 25 mg ml-1 ß-TCP extract had more significant immune responses and switched to the M2 phenotype. Expression levels of the Wnt signaling pathway modulators wingless-type MMTV integration site family, member 6 (WNT6) and Wnt inhibitory factor 1 (WIF1) were upregulated and downregulated, respectively, in macrophages treated with ß-TCP extract. Our findings suggest that ß-TCP enhances osteogenic differentiation of BMSCs by inducing macrophage polarization and by regulating the Wnt signaling pathway, thereby highlighting its therapeutic potential for bone healing through osteoimmunomodulatory properties.
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Células da Medula Óssea/citologia , Substitutos Ósseos/química , Fosfatos de Cálcio/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células-Tronco Mesenquimais/citologia , Osteogênese , Animais , Materiais Biocompatíveis/química , Transplante Ósseo/métodos , Técnicas de Cultura de Células , Diferenciação Celular , Técnicas de Cocultura , Perfilação da Expressão Gênica , Sistema Imunitário , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteínas Wnt/metabolismoRESUMO
PURPOSE: Based on Q methodology, this study investigated the motivation of orthodontic treatment for patients and their parents. Through investigation, this paper attempts to explore the motivational factors of CLP and NON-CLP children and their parents, which are different or general. PATIENTS AND METHODS: Q methodology involves 4 phases. (1) Interviews of CLP (N=5), NON-CLP (N=5) patients generated 30 statements (Q-set 1) and CLP (N=5), NON-CLP (N=5) patients' parents produced 36 statements (Q-set 2) about different reasons to pursue orthodontic care. (2) P-set: recruitment participants. The sample comprised 40 CLP patients (G1) and 40 NON-CLP patients (G2) aged 9-16 years, 40 CLP patients' parents (G3) and 40 NON-CLP patients' parents (G4) wanting their children to have orthodontic treatment. (3) Q-sort: 4 groups ranked statements in order of comparative significance using enforced distribution grids (G1, G2 ranked Q-set 1; G3, G4 ranked Q-set 2). (4) Analysis: using the PQMehtod 2.35 vision to analyze data. RESULTS: Three factors in each group were identified as representing the most widespread views of the majority of the participants, described as G1: (1) aesthetics, (2) preparation for other oral treatments, (3) timely. G2: (1) admiration of others, aesthetics, (2) oral function, (3) oral hygiene and improvement of smile. G3: (1) worrying about the future of children, parents' responsibilities, children's feelings; (2) mental health, timely; (3) parents' responsibilities, ready for treatment. G4: (1) aesthetics, children's will; (2) future problems, timely; (3) timely, parents' responsibility and no need to worry about physical problems. CONCLUSION: CLP and NON-CLP patients and parents have different orthodontic treatment motives, yet, they still shared 3 global motivation themes, respectively. Consideration of these motives may help clinicians develop their treatment discussions with patients and parents, which could consequently improve their cooperation and may achieve a more satisfactory outcome.
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The fibroblast growth factors (FGFs) play a critical role during palatogenesis by mediating a variety of cellular responses. Extensive epidemiological and genetic studies over several decades in humans have revealed members of the FGF family function as candidate genes for syndromic and nonsyndromic cleft lip and cleft palate. The findings that FGFs signaling work delicately in the development of palate have been confirmed in mice carrying targeted mutations. Here we try to review recent progress toward a detailed understanding of FGF signaling including FGF7, FGF8, FGF9, FGF10, FGF18 and their receptors FGFR1, FGFR2 in palate development studies and discuss how they interact with other factors on the basis of animal studies regarding cleft palate.