Analysis of Survival Quality of Peroneal Artery Perforator Flap in Immediate Repairment and Reconstruction of Oral and Maxillofacial Malignancies.

OBJECTIVE: This study aimed to investigate the survival quality of peroneal artery perforator flap in the reconstruction of oral and maxillofacial malignant tumors. METHODS: Thirty-two cases with a diagnosis of oral and maxillofacial malignant tumors admitted to our hospital from January 2019 to December 2019 were randomly divided into 2 groups. The observation group was reconstructed with free open artery perforator flaps, and the control group was repaired with free forearm flaps. RESULTS: The observation group had significantly lower scores in terms of postoperative pain, appearance, and anxiety, compared with the control group ( P <0.05). Both groups had high scores on taste, saliva, and shoulder function although there was no significant difference ( P >0.05). The scores of the observation group were significantly higher than those in the control group in terms of chewing, swallowing, speech, activity, mood, and entertainment ( P <0.05). There was 1 case accompanied by postoperative wound dehiscence and 2 cases with wound infection in the observation group while there were 3 cases with wound dehiscence and 2 cases with wound infection in the control group ( P >0.05). CONCLUSION: Compared with the forearm flap, the peroneal artery perforator flap can improve the survival quality of patients, especially in postoperative function with the fibula joint to repair the oral and maxillofacial defects. It has a wide application prospect as one of the ideal flaps in oral and maxillofacial postoperative repair and reconstruction.

Lysophosphatidic Acid/Polydopamine-Modified nHA Composite Scaffolds for Enhanced Osteogenesis via Upregulating the Wnt/Beta-Catenin Pathway.

Guided bone regeneration (GBR) technology has been widely used for the regeneration of periodontal bone defects. However, the limited mechanical properties and bone regeneration potential of the currently available GBR membranes often limit their repair effectiveness. In this paper, serum-derived growth factor lysophosphatidic acid (LPA) nanoparticles and dopamine-decorative nanohydroxyapatite (pDA/nHA) particles were double-loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as an organic/inorganic biphase delivery system, namely, PP-pDA/nHA-LPA scaffolds. Physicochemical properties and osteogenic ability in vitro and in vivo were performed. Scanning electron microscopy and mechanical tests showed that the PP-pDA/nHA-LPA scaffolds had a 3D bionic scaffold structure with improved mechanical properties. In vitro cell experiments demonstrated that the PP-pDA/nHA-LPA scaffolds could significantly enhance the attachment, proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. In vivo, the PP-pDA/nHA-LPA scaffolds exhibited great cytocompatibility and cell recruitment ability in 2- and 4-week subcutaneous implantation experiments and significantly promoted bone regeneration in the periodontal defect scaffold implantation experiment. Moreover, LPA-loaded scaffolds were confirmed to enhance osteogenic activities by upregulating the expression of ß-catenin and further activating the Wnt/ß-catenin pathway. These results demonstrate that the biphase PP-pDA/nHA-LPA delivery system is a promising material for the GBR.

Correlation between cuspal inclination and tooth cracked syndrome: a three-dimensional reconstruction measurement and finite element analysis.

BACKGROUND/AIM: This paper explored the correlation between cuspal inclination and tooth cracked syndrome by measuring and reconstructing the cuspal inclinations of cracked maxillary first molars through three-dimensional (3D) finite element analysis (FEA). MATERIAL AND METHODS: The cuspal inclinations of 11 maxillary left first molars with cracked tooth syndrome and 22 intact controls were measured by 3D reconstruction. The mean values of each group were used to construct two 3D finite element models of maxillary first molar for comparing stress distribution under the loads of 200N at 0°, 45°, and 90°, respectively, to the tooth axis. RESULTS: There was statistically significant difference in the cuspal inclination between the incompletely fractured group and the intact control group ( P  < 0.001), which was 5.5-6.7 degrees steeper. The model from the mean cuspal inclinations of the incompletely fractured molars showed the maximum tensile stress of 5.83, 10.87, and 25.32 MPa, respectively, in comparison with 5.40, 8.49, and 22.76 MPa for the model of the control group. Besides, the tensile stress was mainly at the center groove and cervical region of the molar model. CONCLUSIONS: Steeper cuspal inclinations resulted in an increment in tensile stress that was mainly at the center groove and cervical region of the molar model under equivalent loads. Higher unfavorable tensile stress was generated with the increasing horizontal component load on the cuspal incline. This indicates an effective reduction of cuspal inclination to the compromised teeth for dentists.

Spatial Delivery of Triple Functional Nanoparticles via an Extracellular Matrix-Mimicking Coaxial Scaffold Synergistically Enhancing Bone Regeneration.

It remains a major challenge to simultaneously achieve bone regeneration and prevent infection in the complex microenvironment of repairing bone defects. Here, we developed a novel ECM-mimicking scaffold by coaxial electrospinning to be endowed with multibiological functions. Lysophosphatidic acid (LPA) and zinc oxide (ZnO) nanoparticles were loaded into the poly-lactic-co-glycolic acid/polycaprolactone (PLGA/PCL, PP) sheath layer of coaxial nanofibers, and deferoxamine (DFO) nanoparticles were loaded into its core layer. The novel scaffold PP-LPA-ZnO/DFO maintained a porous nanofibrous architecture after incorporating three active nanoparticles, showing better physicochemical properties and eximious biocompatibility. In vitro studies showed that the bio-scaffold loaded with LPA nanoparticles had excellent cell adhesion, proliferation, and differentiation for MC3T3-E1 cells and synergistic osteogenesis with the addition of ZnO and DFO nanoparticles. Further, the PP-LPA-ZnO/DFO scaffold promoted tube formation and facilitated the expression of vascular endothelial markers in HUVECs. In vitro antibacterial studies against Escherichia Coli and Staphylococcus aureus demonstrated effective antibacterial activity of the PP-LPA-ZnO/DFO scaffold. In vivo studies showed that the PP-LPA-ZnO/DFO scaffold exhibited excellent biocompatibility after subcutaneous implantation and remarkable osteogenesis at 4 weeks post-implantation in the mouse alveolar bone defects. Importantly, the PP-LPA-ZnO/DFO scaffold showed significant antibacterial activity, prominent neovascularization, and new bone formation in the rat fenestration defect model. Overall, the spatially sustained release of LPA, ZnO, and DFO nanoparticles through the coaxial scaffold synergistically enhanced biocompatibility, osteogenesis, angiogenesis, and effective antibacterial properties, which is ultimately beneficial for bone regeneration. This project provides the optimized design of bone regenerative biomaterials and a new strategy for bone regeneration, especially in the potentially infected microenvironment.

Long-acting PFI-2 small molecule release and multilayer scaffold design achieve extensive new formation of complex periodontal tissues with unprecedented fidelity.

The faithful engineering of complex human tissues such as the bone/soft tissue/mineralized tissue interface in periodontal tissues requires innovative molecular cues in conjunction with tailored scaffolds. To address the loss of periodontal bone and connective tissues following periodontal disease, we have generated a polydopamine and collagen coated electrospun PLGA-PCL (PP) scaffold enriched with the small molecule mediator PFI-2 (PP-PFI-pDA-COL-PFI). In vitro 3D studies using PDL progenitors revealed that the PP-PFI-pDA-COL-PFI scaffold substantially enhanced Alizarin Red staining, increased Ca/P ratios 4-fold, and stimulated cell proliferation more than 12-fold compared to PP-controls, suggestive of its potential for mineralized tissue engineering. When applied in our experimental periodontitis model, the PP-PFI-pDA-COL-PFI scaffold resulted in a substantial 34% reduction in alveolar bone defect height, a 25% root-length gain in periodontal attachment, and the formation of highly ordered regenerated acellular cementum twice as thick as in controls. Explaining the mechanism of PFI-2 mineralized tissue regeneration in periodontal tissues, PFI-2 inhibited SETD7-mediated ß-Catenin protein methylation and increased ß-Catenin nuclear localization. Together, dual-level PFI-2 incorporation into a degradable, dopamine/collagen coated PLGA/PCL scaffold backbone resulted in the regeneration of the tripartite periodontal complex with unprecedented fidelity, including periodontal attachment and new formation of mineralized tissues in inflamed periodontal environments.

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials.

Some cancers such as human breast cancer, prostate cancer, and lung cancer easily metastasize to bone, leading to osteolysis and bone destruction accompanied by a complicated microenvironment. Systemic administration of bisphosphonates (BP) or denosumab is the routine therapy for osteolysis but with non-negligible side effects such as mandibular osteonecrosis and hypocalcemia. Thus, it is imperative to exploit optimized drug delivery systems, and some novel nanotechnology and nanomaterials have opened new horizons for scientists. Targeted and local drug delivery systems can optimize biodistribution depending on nanoparticles (NPs) or microspheres (MS) and implantable biomaterials with the controllable property. Drug delivery kinetics can be optimized by smart and sustained/local drug delivery systems for responsive delivery and sustained delivery. These delicately fabricated drug delivery systems with special matrix, structure, morphology, and modification can minimize unexpected toxicity caused by systemic delivery and achieve desired effects through integrating multiple drugs or multiple functions. This review summarized recent studies about optimized drug delivery systems for the treatment of cancer metastatic osteolysis, aimed at giving some inspiration in designing efficient multifunctional drug delivery systems.

Effect of Orthodontic Treatment on Anterior Tooth Displacement in Patients with Periodontal Disease: A Meta-Analysis.

OBJECTIVE: To systematically evaluate the effect of orthodontic treatment (ODT) on anterior tooth displacement (ATD) in patients with periodontal disease. METHODS: PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang databases were electronically searched for relevant literature studies on ODT and basic treatment for ATD in patients with periodontal disease, and then the related journals and reference lists of the included studies were manually searched. The search time was set from January 2010 to May 2021. Stata 16.0 software was used for meta-analysis. RESULTS: Totally, 783 articles were retrieved, and finally, 14 studies were included. The effective rate of basic treatment combined with OTD was significantly higher than that of basic treatment alone (OR = 7.27, 95% CI: 3.76, 14.04). Specifically, the combined treatment led to lower values of periodontal pocket depth (SMD = -2.30, 95% CI: -2.94, -1.66), anterior overjet (SMD = -2.75, 95% CI: -3.72, -1.78), anterior overbite (SMD = -2.13, 95% CI: -3.16, -1.10), and periodontal bleeding index (SMD = -4.25, 95% CI: -5.48, -3.03) compared with those of basic treatment alone. CONCLUSION: Compared with basic treatment, ODT combined with basic treatment is more effective for patients with periodontal disease-caused ATD and can also improve the clinical symptoms of patients.

Superparamagnetic core-shell electrospun scaffolds with sustained release of IONPs facilitating in vitro and in vivo bone regeneration.

Bone tissue engineering (BTE) is a promising approach to recover insufficient bone in dental implantations. However, the clinical application of BTE scaffolds is limited by their low mechanical strength and lack of osteoinduction. In an attempt to circumvent these limitations and improve osteogenesis, we introduced magnetic iron oxide nanoparticles (IONPs) into a core-shell porous electrospun scaffold and evaluated their impact on the physical, mechanical, and biological properties of the scaffold. We used poly(lactic-co-glycolic acid)/polycaprolactone/beta-tricalcium phosphate (PPT) scaffolds with and without γ-Fe2O3 encapsulation, namely PPT-Fe scaffolds and PPT scaffolds, respectively. The γ-Fe2O3 used in the PPT-Fe scaffolds was coated with polyglucose sorbitol carboxymethylether and was biocompatible. Structurally, PPT-Fe scaffolds showed uniform iron distribution encapsulated within the resorbable PPT scaffolds, and these scaffolds supported sustainable iron release. Furthermore, compared with PPT scaffolds, PPT-Fe scaffolds showed significantly better physical and mechanical properties, including wettability, superparamagnetism, hardness, tensile strength, and elasticity modulus. In vitro tests of rat adipose-derived mesenchymal stem cells (rADSCs) seeded onto the scaffolds showed increased expression of integrin ß1, alkaline phosphatase, and osteogenesis-related genes. In addition, enhanced in vivo bone regeneration was observed after implanting PPT-Fe scaffolds in rat calvarial bone defects. Thus, we can conclude that the incorporation of IONPs into porous scaffolds for long-term release can provide a new strategy for BTE scaffold optimization and is a promising approach that can offer enhanced osteogenic capacity in clinical applications.

Maxillofacial space infection experience and risk factors: a retrospective study of 222 cases.

BACKGROUND: Maxillofacial space infection (MSI) experience review is beneficial for its management. AIM: To identify potential risk factors predisposing to the exacerbation of MSI and a prolonged length of stay (LOS). METHODS: We performed a comprehensive retrospective review of medical records of 222 MSI patients admitted in Center of Stomatology during 1993-2019. RESULTS: About 63.5% of 222 patients had an odontogenic infection, and submandibular space was the most involved space. Streptococcus spp. was the most common organism isolated (72.4%). Multiple-space cases had more systemic diseases, respiratory difficulty, and life-threatening complications and exhibited worse clinical characteristics (higher white-blood-cell-count, higher body temperature, and restricted mouth opening) than single-space cases (P < 0.05). No significant difference in LOS was found between multiple-space cases and single-space cases. Diabetes and hypertension both accounted for 35.1% in life-threatening cases. Multiple-space infection (60.4%), respiratory difficulty (11.7%), and systemic conditions (43.2%) were identified as critical risk factors associated with life-threatening complications in MSI patients (P < 0.001). A significantly prolonged LOS was found in cases aged ≥ 60 years or with systemic diseases. Community outpatient treatment shortened 1.9 days of LOS compared with self-medication before admission during 2010-2019 (P < 0.05). CONCLUSION: Comprehensive managements are advisable for MSI patients with multiple-space infection, respiratory difficulty, systemic diseases to avoid disseminated exacerbation, and occurrence of life-threatening complications. Community outpatient treatment was beneficial to a reduced LOS. Timely access to dental outpatient management and simultaneously steady control of diabetes and hypertension was advocated. Improved coverage of insured dental outpatient treatment should be stressed.

Triple PLGA/PCL Scaffold Modification Including Silver Impregnation, Collagen Coating, and Electrospinning Significantly Improve Biocompatibility, Antimicrobial, and Osteogenic Properties for Orofacial Tissue Regeneration.

Biodegradable synthetic scaffolds hold great promise for oral and craniofacial guided tissue regeneration and bone regeneration. To overcome the limitations of current scaffold materials in terms of osteogenic and antimicrobial properties, we have developed a novel silver-modified/collagen-coated electrospun poly-lactic-co-glycolic acid/polycaprolactone (PLGA/PCL) scaffold (PP-pDA-Ag-COL) with improved antimicrobial and osteogenic properties. Our novel scaffold was generated by electrospinning a basic PLGA/PCL matrix, followed by silver nanoparticles (AgNPs) impregnation via in situ reduction, polydopamine coating, and then coating by collagen I. The three intermediate materials involved in the fabrication of our scaffolds, namely, PLGA/PCL (PP), PLGA/PCL-polydopamine (PP-pDA), and PLGA/PCL-polydopamine-Ag (PP-pDA-Ag), were used as control scaffolds. Scanning electron micrographs and mechanical testing indicated that the unique three-dimensional structures with randomly oriented nanofibrous electrospun scaffold architectures, the elasticity modulus, and the tensile strength were maintained after modifications. CCK-8 cell proliferation analysis demonstrated that the PP-pDA-Ag-COL scaffold was associated with higher MC3T3 proliferation rates than the three control scaffolds employed. Scanning electron and fluorescence light microscopy illustrated that PP-pDA-Ag-COL scaffolds significantly enhanced MC3T3 cell adhesion compared to the control scaffolds after 12 and 24 h culture, in tandem with the highest ß1 integrin expression levels, both at the mRNA level and the protein level. Alkaline phosphatase activity, BMP2, and RUNX2 expression levels of MC3T3 cells cultured on PP-pDA-Ag-COL scaffolds for 7 and 14 days were also significantly higher when compared to controls (P < 0.001). There was a wider antibacterial zone associated in PP-pDA-Ag-COL and PP-pDA-Ag scaffolds versus control scaffolds (P < 0.05), and bacterial fluorescence was reduced on the Ag-modified scaffolds after 24 h inoculation against Staphylococcus aureus and Streptococcus mutans. In a mouse periodontal disease model, the PP-pDA-Ag-COL scaffold enhanced alveolar bone regeneration (31.8%) and was effective for periodontitis treatment. These results demonstrate that our novel PP-pDA-Ag-COL scaffold enhanced biocompatibility and osteogenic and antibacterial properties and has therapeutic potential for alveolar/craniofacial bone regeneration.

A novel Alu-mediated microdeletion in the RUNX2 gene in a Chinese patient with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD; OMIM: 119600) is a rare autosomal dominant skeletal dysplasia caused by RUNX2 gene mutations. The present study described a sporadic case with CCD. The clinical data of the proband with CCD was reported and genetic analysis was performed. The proband presented with typical CCD features including supernumerary impacted teeth, bilateral clavicle dysplasia, delayed closure of cranial sutures, and short stature; while his hands were normal. Sequencing analysis of the entire coding region of the RUNX2 gene revealed no pathogenic changes; however, copy-number analysis with the Affymetrix HD array found ~500 kb genomicmicrodeletion. Real-time quantitative PCR validated this microdeletion in the 1-4 exons of the RUNX2 gene. The junction point of the breaking DNA was located in the directly oriented AluSz6 and AluSx repetitive elements, indicating that this microdeletion might be generated through an Alu-Alu mediated mechanism. In addition, this microdeletion existed in 21.8% of the asymptomatic mother's peripheral blood cells, demonstrating that the mosaicism was not associated with CCD phenotypes. In summary, a pathogenic microdeletion in the RUNX2 gene located on chromosome 6 was responsible for CCD.

Biomimetic Domain-Active Electrospun Scaffolds Facilitating Bone Regeneration Synergistically with Antibacterial Efficacy for Bone Defects.

To improve bone regeneration in oral microenvironment, we generated a novel biodegradable, antibacterial, and osteoconductive electrospun PLGA/PCL membrane as an ideal osteogenic scaffold. The novel three-layer membranes were structured with serial layers of electrospun chlorhexidine-doped-PLGA/PCL (PPC), PLGA/PCL (PP), and ß-tricalcium phosphate-doped-PLGA/PCL (PPß). To characterize osteoconductive properties of these membranes, MC3T3-E1 (MC) cultures were seeded onto the membranes for 14 days for evaluation of cell proliferation, morphology and gene/protein expression. In addition, MC cells were cultured onto different surfaces of the three-layer membranes, PPC layer facing MC cells (PPß-PP-PPC) and PPß layer facing MC cells (PPC-PP-PPß) to evaluate surface-material effects. Membrane properties and structures were evaluated. Antibacterial properties against Streptococcus mutans and Staphylococcus aureus were determined. Scanning electron microscope demonstrated smaller interfiber spaces of PPC and PPß-PP-PPC compared to PPß, PPC-PP-PPß, and PP. PPC and PPß-PP-PPC exhibited hydrophilic property. The three-layer membranes (PPC-PP-PPß and PPß-PP-PPC) demonstrated significantly higher Young's modulus (94.99 ± 4.03 MPa and 92.88 ± 4.03 MPa) compared to PP (48.76 ± 18.15 MPa) or PPC (7.92 ± 3.97 MPa) (p < 0.05). No significant difference of cell proliferation was found among any groups at any time point (p > 0.05). Higher expression of integrins were detected at 12 h of cultures on PPC-PP-PPß compared to the controls. Promoted osteoconductive effects of PPC-PP-PPß were revealed by alkaline phosphatase assays and Western blot compared with the controls at 7 and 14 days. PPC, PPC-PP-PPß and PPß-PP-PPC exhibited a significantly wider antibacterial zone against the tested bacteria compared to PP and PPß (p < 0.05). These results suggested that the three-layer electrospun membranes demonstrated superior properties: higher strength, better cell adhesion, and promoted osteoconductive properties compared to single-layer membrane: however, antibacterial properties were exhibited in three-layer electrospun membranes and chlorhexidine-doped single-layer membrane. We concluded that the novel three-layer membranes could be used as a biocompatible scaffold for intraoral bone regeneration due to its enhanced osteoconductive activity and antibacterial effect.

Enhanced Osteogenesis of ADSCs by the Synergistic Effect of Aligned Fibers Containing Collagen I.

The topographical features and material composition of scaffolds have a powerful influence on cell behaviors such as proliferation and differentiation. Here, scaffolds consisting of aligned fibers with incorporated bioactive collagen I were tested for their ability to enhance osteogenesis in vitro. Rat adipose-derived mesenchymal stem cells (ADSCs) were seeded on the scaffolds and their morphology, proliferation, and osteogenic differentiation were examined. Aligned scaffolds with collagen I showed the best osteogenic properties. Also, adhesion-related genes showed the higher expression on aligned scaffolds with collagen I. Our findings indicate that fiber alignment combined with incorporation of collagen I increases the capacity of electrospun scaffolds to induce enhanced and directed osteogenesis. Such scaffolds may, therefore, have potential for improving guided oral bone regeneration.

The preosteoblast response of electrospinning PLGA/PCL nanofibers: effects of biomimetic architecture and collagen I.

Constructing biomimetic structure and incorporating bioactive molecules is an effective strategy to achieve a more favorable cell response. To explore the effect of electrospinning (ES) nanofibrous architecture and collagen I (COL I)-incorporated modification on tuning osteoblast response, a resorbable membrane composed of poly(lactic-co-glycolic acid)/poly(caprolactone) (PLGA/PCL; 7:3 w/w) was developed via ES. COL I was blended into PLGA/PCL solution to prepare composite ES membrane. Notably, relatively better cell response was delivered by the bioactive ES-based membrane which was fabricated by modification of 3,4-dihydroxyphenylalanine and COL I. After investigation by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurement, and mechanical test, polyporous three-dimensional nanofibrous structure with low tensile force and the successful integration of COL I was obtained by the ES method. Compared with traditional PLGA/PCL membrane, the surface hydrophilicity of collagen-incorporated membranes was largely enhanced. The behavior of mouse preosteoblast MC3T3-E1 cell infiltration and proliferation on membranes was studied at 24 and 48 hours. The negative control was fabricated by solvent casting. Evaluation of cell adhesion and morphology demonstrated that all the ES membranes were more favorable for promoting the cell adhesion and spreading than the casting membrane. Cell Counting Kit-8 assays revealed that biomimetic architecture, surface topography, and bioactive properties of membranes were favorable for cell growth. Analysis of ß1 integrin expression level by immunofluorescence indicated that such biomimetic architecture, especially COL I-grafted surface, plays a key role in cell adhesion and proliferation. The real-time polymerase chain reaction suggested that both surface topography and bioactive properties could facilitate the cell adhesion. The combined effect of biomimetic architecture with enhanced surface activity by 3,4-dihydroxyphenylalanine-assisted modification and COL I incorporation of PLGA/PCL electrospun membranes could successfully fill osteogenic defects and allow for better cell proliferation and differentiation.

Improved performance of diatomite-based dental nanocomposite ceramics using layer-by-layer assembly.

To fabricate high-strength diatomite-based ceramics for dental applications, the layer-by-layer technique was used to coat diatomite particles with cationic [poly(allylamine hydrochloride)] and anionic [poly(sodium 4-styrenesulfonate)] polymers to improve the dispersion and adsorption of positively charged nano-ZrO(2) (zirconia) as a reinforcing agent. The modified diatomite particles had reduced particle size, narrower size distribution, and were well dispersed, with good adsorption of nano-ZrO(2). To determine the optimum addition levels for nano-ZrO(2), ceramics containing 0, 20, 25, 30, and 35 wt% nano-ZrO(2) were sintered and characterized by the three-point bending test and microhardness test. In addition to scanning electron microscopy, propagation phase-contrast synchrotron X-ray microtomography was used to examine the internal structure of the ceramics. The addition of 30 wt% nano-ZrO(2) resulted in the highest flexural strength and fracture toughness with reduced porosity. Shear bond strength between the core and veneer of our diatomite ceramics and the most widely used dental ceramics were compared; the shear bond strength value for the diatomite-based ceramics was found to be significantly higher than for other groups (P < 0.05). Our results show that diatomite-based nanocomposite ceramics are good potential candidates for ceramic-based dental materials.