Human ß-defensins and their synthetic analogs: Natural defenders and prospective new drugs of oral health.

As a family of cationic host defense peptides, human ß-defensins (HBDs) are ubiquitous in the oral cavity and are mainly synthesized primarily by epithelial cells, serving as the primary barrier and aiming to prevent microbial invasion, inflammation, and disease while maintaining physiological homeostasis. In recent decades, there has been great interest in their biological functions, structure-activity relationships, mechanisms of action, and therapeutic potential in oral diseases. Meanwhile, researchers are dedicated to improving the properties of HBDs for clinical application. In this review, we first describe the classification, structural characteristics, functions, and mechanisms of HBDs. Next, we cover the role of HBDs and their synthetic analogs in oral diseases, including dental caries and pulp infections, periodontitis, peri-implantitis, fungal/viral infections and oral mucosal diseases, and oral squamous cell carcinoma. Finally, we discuss the limitations and challenges of clinical translation of HBDs and their synthetic analogs, including, but not limited to, stability, bioavailability, antimicrobial activity, resistance, and toxicity. Above all, this review summarizes the biological functions, mechanisms of action, and therapeutic potential of both natural HBDs and their synthetic analogs in oral diseases, as well as the challenges associated with clinical translation, thus providing substantial insights into the laboratory development and clinical application of HBDs in oral diseases.

M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate.

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.

A novel simplified approach for endodontic retrograde surgery in short single-rooted teeth.

BACKGROUND: High technical thresholds, long operative times, and the need for expensive and specialized equipment impede the widespread adoption of endodontic microsurgery in many developing countries. This study aimed to compare the effects of a simplified, cost-effective, and time-efficient surgical approach involving orthograde obturation using biological ceramic material greater than 6 mm combined with apicoectomy for single-rooted teeth with short lengths with those of the conventional and current standard methods. MATERIALS AND METHODS: Forty-five premolars equally categorized into three groups: conventional surgery group, standard surgery group, and modified surgery group. A µCT scan was used to calculate the volume of voids. A micro-leakage test and scanning electron microscope (SEM) were performed to assess the sealing effect. Additionally, four cases of chronic periapical periodontitis in the anterior region were selected, and the patients received either the modified approach or the standard surgery for endodontic microsurgery. RESULTS: The volumes of voids in the apical 0-3 mm of the modified group and the standard group were comparable. The micro-leakage test and SEM examination demonstrated closely bonded fillings in the dentinal walls in both the modified surgery group and standard surgery group. The outcomes of the preliminary application of this modified procedure on patients were successful at the time of the follow-up cutoff. CONCLUSIONS: The modified surgery group exhibited similar root canal filling and apical sealing abilities with the standard procedure for single-rooted teeth with short lengths (< 20 mm). The preliminary application of this modified surgical procedure achieved favorable results.

Relevant factors of posterior mandible lingual plate perforation during immediate implant placement: a virtual implant placement study using CBCT.

BACKGROUND: To explore the influence of cross-sectional type and morphological parameters at the mandibular molar sites on lingual plate perforation (LPP) during the immediate implant placement (IIP). METHODS: 181 implants were virtually placed in the mandibular molar sites on the cone beam computed tomography (CBCT). Each cross-section of the implantation site was divided into the Undercut (U)/Parallel (P)/Convex (C) types. Morphologically relevant parameters were measured on the cross-sections, including width of the upper end (Wb), width of the lower end (Wc), vertical height (V), angle between the natural crown axis and the alveolar bone axis (∠ß), LC depth (LCD), LC height, and angle between the horizontal line and the line connecting the most prominent point and the most concave point of lingual plate (∠α). Besides, the distance from the end of the virtual implant and the lingual bone plate of the cross-section (DIL) was calculated. Relationships between all the morphologically relevant parameters and the DIL were further analyzed. RESULTS: A total of 77 (42.5%) cross-sections were classified as U-type, which was the most common one, accounting for 63% of the second molar regions. All LPP cases and most of the nearly LPP (87.9%) cases occurred at the U-type cross-sections, and the relationship between the DIL and the morphological parameters can be expressed by a multivariate linear equation. CONCLUSIONS: The occurrence rate of U-type cross-sections in the second molar region was very high, and the risk of LPP should be considered during IIP. Except for the U-type, significant large LCD, small Wc, and large âˆ ß were the important relevant factors. CBCT and multivariate linear equations could help to assess the LPP risk and provide a reference for implant placement design pre-surgery.

Extracellular Vesicles in Bone Homeostasis: Emerging Mediators of Osteoimmune Interactions and Promising Therapeutic Targets.

An imbalance in bone homeostasis results in bone loss and poor healing in bone diseases and trauma. Osteoimmune interactions, as a key contributor to bone homeostasis, depend on the crosstalk between mesenchymal stem cell-osteoblast (MSC-OB) and monocyte-macrophage (MC-Mφ) lineages. Currently, extracellular vesicles (EVs) are considered to be involved in cell-to-cell communication and represent a novel avenue to enhance our understanding of bone homeostasis and to develop novel diagnostic and therapeutic options. In this comprehensive review, we aim to present recent advances in the study of the effect of MC-Mφ-derived EVs on osteogenesis and the regulatory effects of MSC-OB-derived EVs on the differentiation, recruitment and efferocytosis of Mφ. Furthermore, we discuss the role of EVs as crucial mediators of the communication between these cell lineages involved in the development of common bone diseases, with a focus on osteoporosis, osteoarthritis, bone fracture, and periodontal disease. Together, this review focuses on the apparent discrepancies in current research findings and future directions for translating fundamental insights into clinically relevant EV-based therapies for improving bone health.

Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis.

Stem cell based transplants effectively regenerate tissues; however, limitations such as immune rejection and teratoma formation prevent their application. Extracellular vesicles (EVs)-mediated acellular tissue regeneration is a promising alternative to stem cell based transplants. Although neural EGFL-like 1 (Nell1) is known to contribute to the osteogenic differentiation of bone marrow stem cells (BMSCs), it remains unknown whether EVs are involved in this process. Here, we present that EVs derived from Nell1-modified BMSCs (Nell1/EVs) have a stronger ability to promote BMSC osteogenesis owing to miR-25-5p downregulation. MiR-25-5p inhibits osteogenesis by targeting Smad2 and suppressing the SMAD and extracellular signal-related kinase 1 and 2 (ERK1/2) pathway activation. In addition, we demonstrate that the 3D-Nell1/EV-hydrogel system is beneficial for bone regeneration in vivo, probably stemming from a slow, continuous release and high concentration of EVs in the bone defect area. Thus, our results have shown the potential of Nell1/EVs as a novel acellular bone regeneration strategy. Mechanistically, the identification of miR-25-5p-SMAD2 signaling axis expands the knowledge of Nell1/EVs induced osteogenesis.

The comparative evaluation of transcrestal and lateral sinus floor elevation in sites with residual bone height ≤6 mm: A two-year prospective randomized study.

OBJECTIVES: To compare clinical and radiographic outcomes between transcrestal sinus floor elevation (TSFE) and lateral sinus floor elevation (LSFE) approaches of simultaneous implant placement in atrophic maxilla. MATERIALS AND METHODS: Patients with a residual bone height (RBH) ≤6 mm were enrolled and randomly assigned to TSFE and LSFE groups. Patients in both groups simultaneously underwent sinus floor elevation with bovine-derived xenograft and implant placement. Clinical and radiographic results were evaluated immediately after surgery and after 6, 12, 18, and 24 months. The endo-sinus bone gain (ESBG), apical implant bone height (ABH), endo-sinus bone-implant contact rate (EBICR), and crestal bone level (CBL) were assessed using panoramic radiographs. RESULTS: Forty-one implants (TSFE: 21, LSFE: 20) were placed in cases with a mean RBH of 3.77 ± 1.16 mm. All implants obtained clinical success and satisfactory ESBG at 24 months. No significant differences were found in ESBG and ABH between two groups immediately after surgery, but LSFE group showed significantly higher values than TSFE group thereafter. Grafts in TSFE group reached stability 6 months earlier than that in LSFE group. In both groups, EBICR was almost 100%, and CBL showed no detectable changes. CONCLUSIONS: LSFE can achieve higher ESBG 2 years after surgery. Otherwise, TSFE could be an alternative to LSFE, when the access for lateral window preparation is limited. Both approaches were highly predictable for RBH ≤6 mm during 24-month observation period for the implants placed simultaneously.

Exosomes Enhance Adhesion and Osteogenic Differentiation of Initial Bone Marrow Stem Cells on Titanium Surfaces.

Successful osseointegration involves the biological behavior of bone marrow stem cells (BMSCs) on an implant surface; however, the role of BMSC-derived extracellular vesicles (EVs)/exosomes in osseointegration is little known. This study aimed to: (i) explore the interaction force between exosomes (Exo) and cells on a titanium surface; (ii) discuss whether the morphology and biological behavior of BMSCs are affected by exosomes; and (iii) preliminarily investigate the mechanism by which exosomes regulate cells on Ti surface. Exosomes secreted by rat BMSCs were collected by ultracentrifugation and analyzed using transmission electron microscopy and nanoparticle tracking analysis. Confocal fluorescence microscopy, scanning electron microscopy, Cell Counting Kit-8 (CCK-8), quantitative real-time polymerase chain reaction techniques, and alkaline phosphatase bioactivity, Alizarin Red staining, and quantification were used to investigate the exosomes that adhere to the Ti plates under different treatments as well as the morphological change, adhesion, spread, and differentiation of BMSCs. We found that exosomes were efficiently internalized and could regulate cell morphology and promoted the adhesion, spreading, and osteogenic differentiation of BMSCs. These were achieved partly by activating the RhoA/ROCK signaling pathway. Our discovery presents a new insight into the positive regulatory effect of exosomes on the biological behaviors of BMSCs on Ti surface and provides a novel route to modify the surface of a Ti implant.

Displacement and stress distribution of the maxilla under different surgical conditions in three typical models with bone-borne distraction: a three-dimensional finite element analysis.

OBJECTIVE: The present study compared the skeletal effects of surgically assisted rapid maxillary expansion (SARME) with different surgeries in three representative finite element (FE) models. STUDY DESIGN: According to the ossification level of midpalatal suture, three FE models, with different elasticity moduli of sutures (E = 1 MPa, 500 MPa, and 13,700 MPa) were constructed, to represent three age groups of patients. Within each model, four groups were set up according to different surgeries: group I (control group without surgery), II (paramedian osteotomy), III (pterygomaxillary separation), and IV (paramedian osteotomy and pterygomaxillary separation). An expansion force of 100 N and 1 mm displacement were applied via a bone-borne distraction to simulate the expansion process. RESULTS: By analyzing these models, the maximum displacement of maxilla was observed in group IV, with E = 1 MPa model exhibiting the most displacement (28.5â€¯× 10-6 mm), followed by group II (21.4â€¯× 10-6 mm). Group IV showed a unique backward-downward rotation with minimum stress distributions in three models (9 MPa, 131 MPa, and 140 MPa, respectively), and group II exhibited comparable low stress distributions (12 MPa, 151 MPa, and 230 MPa, respectively). Lowest stress was found in E = 1 MPa model, compared with the other two models. CONCLUSION: There is no need to perform surgeries when the midpalatal suture is open, and surgery guidelines are the same for partial and complete fusion sutures. Furthermore, exclusive use of partial paramedian osteotomy is sufficient enough to reduce stress and expand the posterior part of maxilla, and it is less invasive.

Stem-cell-derived ECM sheet-implant complexes for enhancing osseointegration.

Numerous treatment methods have been developed to modify the surface of dental implants to improve cell migration and proliferation, removal torque, and osseointegration. Recent studies have constructed cell sheet-implant complexes with enhanced osteogenic capabilities. However, these complexes have some limitations, such as requirements for complex preparation processes, cell vitality maintenance, strict preservation conditions, and the induction of immunogenicity. Extracellular matrix (ECM) sheets without cells may be a more desirable material. To date, the effect of ECM sheets on implant osseointegration has not been reported. In this study, we fabricated ECM sheet-implant complexes through the combination of rat bone marrow mesenchymal stem cell (BMSC)-derived ECM sheets with sandblasted, large-grit, acid-etched (SLA) implants. These complexes were characterized by light microscopy, scanning electron microscopy (SEM), and immunofluorescence (IF) assays. The adhesion, proliferation, and osteogenic differentiation of BMSCs cultured on ECM sheets were detected in vitro. Then, the ECM sheet-implant complexes were transplanted into the metaphysis of the tibias of rats to evaluate the implant osseointegration in vivo. The results showed that ECM sheets were successfully constructed and showed significantly improved adhesion and proliferation. BMSCs cultured on ECM sheets upregulated the expression levels of the osteogenic-related genes alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (Runx2) compared to controls. In vivo, ECM sheet-implant complexes demonstrated superior new bone formation. Our findings proved that the BMSC-derived ECM sheets promoted osseointegration in vitro and in vivo. The current study indicated that the ECM sheet could be an ideal tissue engineering material, and ECM sheet-implant complexes could provide a strategy with low immunogenicity and easy storage and transportation. This research provides a novel strategy for the development of implant surface modification approaches.

NEMO­binding domain peptide ameliorates inflammatory bone destruction in a Staphylococcus aureus­induced chronic osteomyelitis model.

Osteomyelitis, which is characterized by progressive inflammatory bone destruction and resorption, is a difficult­to­treat infection. Staphylococcus aureus (S. aureus) is one of the major causes of this disease. This pathogenic microorganism possesses several characteristics, which facilitate its involvement in the occurrence and progression of osteomyelitis. A cell­permeable peptide inhibitor of the IκB kinase complex, the nuclear factor (NF)­κB essential modulator­binding domain (NBD) peptide, has been reported to block osteoclastogenesis and may be considered a potential strategy for preventing inflammatory bone resorption. However, it remains to be determined as to whether the NBD peptide can regulate inflammation and bone resorption in S. aureus­induced osteomyelitis. In order to investigate the role of NBD in S. aureus­induced osteomyelitis, the present study obtained the NBD peptide, and confirmed that it inhibited receptor activator of NF­κB ligand­induced osteoclastogenesis in vitro. Subsequently, a bone defect was generated and S. aureus was injected into the mandible of experimental animals, in order to establish an in vivo osteomyelitis model. The present study analyzed the following three experimental groups: Untreated, treated with debridement, and treated with debridement plus NBD peptide administration. The results revealed that treatment with the NBD peptide reduced the bone defect in a 3­dimensional manner, and reduced bone resorption. To the best of our knowledge, the present study is the first to demonstrate that, in a model of osteomyelitis caused by S. aureus, the NBD peptide serves a role in inhibiting osteolysis and promoting bone remodeling in the direction of osteogenesis. The effects were better than those produced by debridement alone, thus suggesting that it may have promising therapeutic potential in osteomyelitis.

Clinician, dental student, and orthognathic patient perception of black-and-white silhouette lateral profile dimensions of ideal chin position in a Chinese population.

OBJECTIVES: This study aimed to investigate differences in the influence of chin prominence and length on perception of facial aesthetics by Chinese dental clinicians, orthognathic patients, and dental students. STUDY DESIGN: Male and female silhouette lateral profiles were modified to obtain 28 facial profiles by altering chin prominence and length by 3 mm in the sagittal and vertical planes. Images were rated by 70 clinicians, 30 orthognathic patients, and 100 dental students on a 7-point Likert scale. RESULTS: Perceived attractiveness was highest when the male chin prominence (MCP) was -3 mm to 3 mm and the female chin prominence (FCP) was 3 mm. In contrast, male chin length (MCL) of 0 to 3 mm and female chin length (FCL) of 0 mm were considered the most attractive. In the sagittal and vertical profiles, MCP (-9 mm), FCP (-9 mm), FCL (-9 mm), and MCL (-9 mm) were ranked least attractive. CONCLUSIONS: The overall aesthetic opinions of orthognathic patients, clinicians, and dental students are similar. The greater the retrusion or protrusion of the chin and the shorter or longer the chin length, the lower were the rates of facial aesthetics and the greater were the desire for surgery.

Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced by andrographolide via upregulation of phospho-p53 in vitro and in vivo.

Oral squamous cell carcinoma is one of the most common neoplasm in the world. Despite the improvements in diagnosis and treatment, the outcome is still poor now. Thus, the development of novel therapeuticapproaches is needed. The aim of this study is to assess the synergistic anti-tumor effect of andrographolide with cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and western blotting on CAL-27 cells treated with andrographolide, DDP or the combination in vitro. In vivo, we also treated CAL-27 xenografts with andrographolide or the combination, and performed terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis of Ki-67. The results showed the combination of andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition, the synergistic anti-tumor effect of andrographolide with synergistic was due to an enhanced apoptosis. Moreover, the combination therapy upregulated the expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our data indicate that the combination treatment of andrographolide and DDP results in synergistic anti-tumor growth activity against oral squamous cell carcinoma CAL-27 in vitro and in vivo. These results demonstrated that combination of andrographolide with DDP was likely to represent a potential therapeutic strategy for oral squamous cell carcinoma.

Enhanced osteogenic differentiation of rat bone marrow mesenchymal stem cells on titanium substrates by inhibiting Notch3.

OBJECTIVE: The role of the Notch pathway has already been identified as a crucial regulator of bone development. However, the Notch signaling pathway has gone largely unexplored during osseointegration. This study aims to investigate the role of Notch signaling on osteogenic differentiation of rat derived bone marrow mesenchymal stem cells (BMSCs) on sandblasted, large-grit, acid-etched (SLA) treated Ti disks. METHODS: The involved target genes in Notch pathways were identified by in vitro microarray and bioinformatics analyses with or without osteogenic induction. Adhesion, proliferation, and osteogenic related assay were subsequently conducted with target gene shRNA treatment. RESULTS: We found that 11 genes in the Notch signaling pathway were differentially expressed after osteogenic induction on SLA-treated Ti disks, which included up-regulated genes (Notch2, Dll1, Dll3, Ncstn, Ncor2, and Hes5) and down-regulated genes (Notch3, Lfng, Mfng, Jag2 and Maml2). With Notch3 shRNA treatment, the adhesion and proliferation of BMSCs on SLA-treated Ti disks were inhibited. Moreover, the expression levels of alkaline phosphatase (ALP), osteocalcin (OCN), calcium deposition, BMP2 and Runx2 increased significantly compared with that observed in control groups, suggesting that the function of Notch3 was inhibitory in the osteogenic differentiation of BMSCs on SLA-treated titanium. CONCLUSIONS: Inhibition Notch3 can enhance osteogenic differentiation of BMSCs on SLA-treated Ti disks, which potentially provides a gene target for improving osseointegration.

Asperosaponin VI promotes bone marrow stromal cell osteogenic differentiation through the PI3K/AKT signaling pathway in an osteoporosis model.

Asperosaponin VI (ASA VI), a natural compound isolated from the well-known traditional Chinese herb Radix Dipsaci, has an important role in promoting osteoblast formation. However, its effects on osteoblasts in the context of osteoporosis is unknown. This study aimed to investigate the effects and mechanism of ASA VI action on the proliferation and osteogenic differentiation of bone marrow stromal cells isolated from the ovariectomized rats (OVX rBMSCs). The toxicity of ASA VI and its effects on the proliferation of OVX rBMSCs were measured using a CCK-8 assay. Various osteogenic differentiation markers were also analyzed, such as ALP activity, calcified nodule formation, and the expression of osteogenic genes, i.e., ALP, OCN, COL 1 and RUNX2. The results indicated that ASA VI promoted the proliferation of OVX rBMSCs and enhanced ALP activity and calcified nodule formation. In addition, while ASA VI enhanced the expression of ALP, OCN, Col 1 and RUNX2, treatment with LY294002 reduced all of these osteogenic effects and reduced the p-AKT levels induced by ASA VI. These results suggest that ASA VI promotes the osteogenic differentiation of OVX rBMSCs by acting on the phosphatidylinositol-3 kinase/AKT signaling pathway.

Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells.

Circuit simulation is a powerful methodology to generate differential mathematical models. Due to its highly accurate modeling capability, circuit simulation can be used to investigate interactions between the parts and processes of a cellular system. Circuit simulation has become a core technology for the field of electrical engineering, but its application in biology has not yet been fully realized. As a case study for evaluating the more advanced features of a circuit simulation tool called Advanced Design System (ADS), we collected and modeled laboratory data for iron metabolism in mouse kidney cells for a H ferritin (HFt) receptor, T cell immunoglobulin and mucin domain-2 (TIM-2). The internal controlling parameters of TIM-2 associated iron metabolism were extracted and the ratios of iron movement among cellular compartments were quantified by ADS. The differential model processed by circuit simulation demonstrated a capability to identify variables and predict outcomes that could not be readily measured by in vitro experiments. For example, an initial rate of uptake of iron-loaded HFt (Fe-HFt) was 2.17 pmol per million cells. TIM-2 binding probability with Fe-HFt was 16.6%. An average of 8.5 min was required for the complex of TIM-2 and Fe-HFt to form an endosome. The endosome containing HFt lasted roughly 2 h. At the end of endocytosis, about 28% HFt remained intact and the rest was degraded. Iron released from degraded HFt was in the labile iron pool (LIP) and stimulated the generation of endogenous HFt for new storage. Both experimental data and the model showed that TIM-2 was not involved in the process of iron export. The extracted internal controlling parameters successfully captured the complexity of TIM-2 pathway and the use of circuit simulation-based modeling across a wider range of cellular systems is the next step for validating the significance and utility of this method.

Tensile force produced by a lipoma in the masseteric space possibly causing hyperostosis of the angle of the mandible.

BACKGROUND: A lipoma is a benign tumor which may occur in the adipose tissue of any part of the body. The tumor is most commonly found on the trunk and extremities. Although it is the most common tumor of mesenchymal origin in the head and neck, its incidence is relatively rare. Lipoma of the head and neck is usually located in subcutaneous tissue. It is rarely deep seated with osseous involvement and rarely occurs in children, especially below the age of 10. CASE REPORT: The case of a painless mass of one-year history in the right parotidomasseteric region of an eight-year-old boy is presented. The mass was revealed to be a classical lipoma in the masseteric space, possibly causing hyperostosis of the angle of the mandible. After removal of the mass and a spherical protuberance in the angle of the mandible, the boy recovered and no recurrence was noted after one-year follow-up. CONCLUSIONS: Hyperostosis is a rare phenomenon with lipoma. In this case, the hypothesis was posed that the tensile force produced by the lipoma in the masseteric space possibly caused hyperostosis of the angle of the mandible. To the authors' knowledge, a classical lipoma arising from the deep fascial space resulting in osseous change has not been described in the literature before.

Designer self-assembling peptide scaffold stimulates pre-osteoblast attachment, spreading and proliferation.

A new peptide scaffold was made by mixing pure RADA16 (Ac-RADARADARADARADA-CONH2) and designer peptide RGDA16 (Ac-RADARGDARADARGDA-CONH2) solutions, and investigate any effect on attachment, spreading and proliferation of pre-osteoblast (MC3T3-E1). The peptides, RADA16 and RGDA16, were custom-synthesized. They were solubilized in deionized water at a concentration of 10 mg/ml (1% w/v), the RGDA16 peptide solution was mixed 1:1 with RADA16 solution and a new peptide solution RGDAmix was produced. The RGDAmix and RADA16 solution were directly loaded in 96-well plates and cover slips, and two different peptide scaffolds were formed with the addition of maintenance medium (alpha-MEM) in several minutes. About 1.0 x 10(4) MC3T3-E1 cells were seeded on each hydrogel scaffold, and then the cell morphological changes were observed using a fluorescence microscope at 1 h, 3 h and 24 h timepoint, respectively. Cell attachment was evaluated 1 h, 3 h and 24 h after cell seeding and cell proliferation was determined 4d, 7d and 14d after cell seeding. The RGDAmix scaffold significantly promoted the initial cell attachment compared with the RADA16 scaffold. MC3T3-E1 cells adhered and spread well on both scaffolds, however, cells spread better on the RGDAmix scaffold than on the RADA16 scaffold. Cell proliferation was greatly stimulated when cultured on RGDAmix scaffold. The RGD sequence contained peptide scaffold RGDAmix significantly enhances MC3T3-E1 cells attachment, spreading and proliferation.

Intraoral granulocytic sarcoma presenting as multiple maxillary and mandibular masses: a case report and literature review.

Granulocytic sarcoma (GS) is an unusual localized tumor composed of immature granulocytic precursor cells that occurs in extramedullary sites. However, GS involving the oral cavity is rare. We report a case of intraoral GS with an unusual clinical presentation, including a history of chronic myelogenous leukemia in remission, multiple maxillary and mandibular gingival masses mimicking acute inflammation that developed over a short period, complete remission after 1 week of treatment with imatinib mesylate (Gleevec), and no bone marrow or peripheral blood involvement over a 6-month follow-up period. To our knowledge, this is the first report of treatment of intraoral GS with Gleevec resulting in a complete remission.