Fabricating nasal prostheses using four-dimensional facial expression models.

Purpose Patients with facial prostheses face challenges such as maintenance of the prosthesis in place, especially around the margins, because of movement of surrounding facial skin. Conventional facial prostheses are fabricated on stationary models based on two points: neutral expression and smiling expression. We developed four-dimensional (4D) facial expression models which shape facial expressions that change over several points in time using a morphing technique. We fabricated facial prostheses using 4D models and evaluated their accuracy and fit compared with prostheses generated with the two-expression technique.Methods Seven patients with nasal defects or nasal deformities participated in this study. Facial expression morphing prostheses were fabricated based on the 4D scanned data of each patient, using five points between neutral expression (0%) and smiling (100%). Five nasal prostheses, one for each point, were evaluated in each patient objectively and subjectively for accuracy and fit.Results On subjective evaluation, the nasal prostheses fabricated using the 4D facial expression models had better marginal sealing over the range from the neutral expression to smiling, and showed better attachment during facial movement on objective evaluation.Conclusions Facial prostheses fabricated using 4D facial expression models provided better marginal sealing than those fabricated using conventional two-point modeling.

Correlation between the relative abundance of oral bacteria and Candida albicans in denture and dental plaques.

OBJECTIVES: The opportunistic fungus Candida albicans is a component of denture plaque and is associated with denture-related stomatitis. Inter-kingdom interactions between C. albicans and bacteria exist in such multi-species biofilms, which may affect the microbial composition of the plaque. This study was performed to investigate the bacterial composition of denture plaques, and the correlation between the relative abundance of these bacteria and C. albicans. METHODS: Thirty denture plaque and 16 dental plaque samples were collected from 18 denture wearers (mean age, 80.3 years). After DNA extraction, a meta 16S rDNA amplicon library was constructed using PCR primers targeting the V3-V4 hypervariable region of bacteria. The amplicon was evaluated by high-throughput sequencing, followed by bacterial population analysis. The concentrations of both C. albicans DNA and total bacterial DNA were determined by real-time PCR. The correlation between the relative abundance of each bacterial genus and C. albicans was analyzed through Spearman's rank correlation. RESULTS: The genera Streptococcus, Lactobacillus, Rothia, and Corynebacterium were found to be more abundant in dentures than in dental plaques. The predominant bacteria in healthcare-associated pneumonia also inhabited denture surfaces. C. albicans was positively correlated with three acidogenic bacteria and negatively correlated with Leptotrichia and pathogens associated with periodontitis and endocarditis. CONCLUSIONS: Dentures may be significant reservoirs of pathogens causing aspiration pneumonia. Bacteria showing negative correlation with C. albicans, such as Leptotrichia, may be useful for controlling the growth of C. albicans in antifungal therapies.

Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects.

BACKGROUND: Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation. METHODS: DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (ß-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation. RESULTS: Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL. CONCLUSIONS: These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

Sustainable Effects of Human Dental Pulp Stem Cell Transplantation on Diabetic Polyneuropathy in Streptozotocine-Induced Type 1 Diabetes Model Mice.

Dental pulp stem cells (DPSCs) are suitable for use in regenerative medicine. Cryopreserved human DPSCs (hDPSCs) ameliorate diabetic polyneuropathy, and the effects of hDPSC transplantation are related to VEGF and NGF secretion. This study evaluated the long-term effects of a single transplantation of hDPSCs on diabetic polyneuropathy. hDPSCs were obtained from human third molars extracted for orthodontic treatment, which were then transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocin injection in nude mice. The effects of hDPSC transplantation were analyzed at 16 weeks post-transplantation. DPSC transplantation significantly improved delayed nerve conduction velocity, decreased blood flow, and increased sensory perception thresholds. Furthermore, the hDPSC-conditioned medium promoted the neurite outgrowth of dorsal root ganglion neurons. In conclusion, the therapeutic effects of hDPSC transplantation with a single injection last for prolonged periods and may be beneficial in treating long-term diabetic polyneuropathy.

Transplantation of human dental pulp stem cells ameliorates diabetic polyneuropathy in streptozotocin-induced diabetic nude mice: the role of angiogenic and neurotrophic factors.

BACKGROUND: Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. In our previous study, we demonstrated that cryopreserved rat DPSCs improved diabetic polyneuropathy and that the efficacy of cryopreserved rat DPSCs was equivalent to that of freshly isolated rat DPSCs. The present study was conducted to evaluate whether transplantation of cryopreserved human DPSCs (hDPSCs) is also effective for the treatment of diabetic polyneuropathy. METHODS: hDPSCs were isolated from human impacted third molars being extracted for orthodontic reasons. Eight weeks after the induction of diabetes in nude mice, hDPSCs (1 × 105/limb) were unilaterally transplanted into the hindlimb skeletal muscle, and vehicle (saline) was injected into the opposite side as a control. The effects of hDPSCs were analyzed at 4 weeks after transplantation. RESULTS: hDPSC transplantation significantly ameliorated reduced sensory perception thresholds, delayed nerve conduction velocity, and decreased the blood flow to the sciatic nerve in diabetic mice 4 weeks post-transplantation. Cultured hDPSCs secreted the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) proteins. A subset of the transplanted hDPSCs was localized around the muscle bundles and expressed the human VEGF and NGF genes at the transplanted site. The capillary/muscle bundle ratio was significantly increased on the hDPSC-transplanted side of the gastrocnemius muscles in diabetic mice. Neutralizing antibodies against VEGF and NGF negated the effects of hDPSC transplantation on the nerve conduction velocity in diabetic mice, suggesting that VEGF and NGF may play roles in the effects of hDPSC transplantation on diabetic polyneuropathy. CONCLUSIONS: These results suggest that stem cell transplantation with hDPSCs may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors.

Type 2 diabetes impairs implant osseointegration capacity in rats.

PURPOSE: The effect of type 2 diabetes mellitus (adult-onset non-insulin-dependent), which is the most common form of diabetes in humans, on osseointegration capacity has not been addressed in an appropriate animal model. This study histologically and histomorphometrically examines bone healing around titanium implants in the type 2 diabetes rat model. MATERIALS AND METHODS: Titanium implants with a chamber were placed into the femurs of normal male rats and genetically modified male rats with a close symptomatic resemblance to human type 2 diabetes, as characterized by late-onset hyperglycemia and obesity. Cross-sectional histology for the tissue grown into the implant chamber was examined. RESULTS: Bone volume around implants was consistently (from weeks 4 to 8 postimplantation) smaller for the diabetes group than for the control group in the cortical area, while the bone volume in the marrow area was not affected by the diabetes. Bone-implant contact percentage was considerably lower for the diabetes group in both the cortical and marrow areas, with the week 4 bone-implant contact in the cortical area being 12% for the diabetes group and 61% for the control group. A 2-fold difference remained at week 8. Bone morphogenesis in the diabetic rats was characterized by fragmented bone tissues and extensive soft tissue intervention. CONCLUSIONS: Type 2 diabetes mellitus impaired osseointegration capacity disproportionally between the cortical bone and bone marrow areas. The reduction of the bone quantity in the cortical area and the bone-implant contact in both the cortical and marrow areas was remarkable.

Transplantation of dental pulp stem cells improves long-term diabetic polyneuropathy together with improvement of nerve morphometrical evaluation.

BACKGROUND: Although previous reports have revealed the therapeutic potential of stem cell transplantation in diabetic polyneuropathy, the effects of cell transplantation on long-term diabetic polyneuropathy have not been investigated. In this study, we investigated whether the transplantation of dental pulp stem cells (DPSCs) ameliorated long-term diabetic polyneuropathy in streptozotocin (STZ)-induced diabetic rats. METHODS: Forty-eight weeks after STZ injection, we transplanted DPSCs into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation (i.e., 52 weeks after STZ injection) the effects of DPSC transplantation on diabetic polyneuropathy were assessed. RESULTS: STZ-induced diabetic rats showed significant reductions in the sciatic motor/sensory nerve conduction velocity, increases in the current perception threshold, and decreases in capillary density in skeletal muscles and intra-epidermal nerve fiber density compared with normal rats, all of which were ameliorated by DPSC transplantation. Furthermore, sural nerve morphometrical analysis revealed that the transplantation of DPSCs significantly increased the myelin thickness and area. DPSC-conditioned media promoted the neurite outgrowth of dorsal root ganglion neurons and increased the viability and myelin-related protein expression of Schwann cells. CONCLUSIONS: These results indicated that the transplantation of DPSCs contributed to the neurophysiological and neuropathological recovery from a long duration of diabetic polyneuropathy.

Reliability and validity of the patient disability-oriented diagnostic nomenclature system for prosthetic dentistry.

PURPOSE: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and improve prosthodontic treatment. This system specifies patient disability and the causative factor (i.e. "B (disability) caused by A (causative factor)"). The purpose of this study was to examine the reliability and validity of this DNS. STUDY SELECTION: The JPS Clinical Guideline Committee assessed mock patient charts and formulated disease names using the new DNS. Fifty validators, comprising prosthodontic specialists and dental residents, made diagnoses using the same patient charts. Reliability was evaluated as the consistency of the disease names among the validators, and validity was evaluated using the concordance rate of the disease names with the reference disease names. RESULTS: Krippendorff's α was 0.378 among all validators, 0.370 among prosthodontic specialists, and 0.401 among dental hospital residents. Krippendorff's α for 10 validators (3 specialists and 7 residents) with higher concordance rates was 0.524. Two validators (1 specialist and 1 resident) with the highest concordance rates had a Krippendorff's α of 0.648. Common disease names had higher concordance rates, while uncommon disease names showed lower concordance rates. These rates did not show correlation with clinical experience of the validator or time taken to devise the disease name. CONCLUSIONS: High reliability was not found among all validators; however, validators with higher concordance rates showed better reliability. Furthermore, common disease names had higher concordance rates. These findings indicate that the new DNS for prosthodontic dentistry exhibits clinically acceptable reliability and validity.

Impact of the haplotype CYP3A4*16B harboring the Thr185Ser substitution on paclitaxel metabolism in Japanese patients with cancer.

OBJECTIVE: Paclitaxel is one of the most important anticancer drugs for the treatment of various tumors such as non-small cell lung cancer. We investigated the association between CYP3A4 haplotypes and pharmacokinetic parameters of paclitaxel metabolism. METHODS: This study enrolled 235 Japanese patients with cancer who were receiving paclitaxel. These patients were screened for CYP3A4 gene polymorphisms by either direct sequencing or pyrosequencing. Plasma concentrations of paclitaxel and its 3 metabolites were determined by HPLC in 229 patients. RESULTS: Median values of paclitaxel clearance, normalized for body surface area, were lower in the high-dose group (>or=175 mg/m2, n = 199) than in the low-dose group (

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy.

AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSCs increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory effects of DPSC transplantation on diabetic peripheral nerves. MATERIALS AND METHODS: DPSCs were isolated from the dental pulp of Sprague-Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection, DPSCs were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation, neurophysiological measurements, inflammatory gene expressions and the number of CD68-positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of DPSCs, the effects of DPSC-conditioned media on lipopolysaccharide-stimulated murine macrophage RAW264.7 cells were investigated. RESULTS: Diabetic rats showed significant delays in sciatic nerve conduction velocities and decreased sciatic nerve blood flow, all of which were ameliorated by DPSC transplantation. The number of CD68-positive monocytes/macrophages and the gene expressions of M1 macrophage-expressed cytokines, tumor necrosis factor-α and interleukin-1ß, were increased in the sciatic nerves of the diabetic rats. DPSC transplantation significantly decreased monocytes/macrophages and tumor necrosis factor-α messenger ribonucleic acid expression, and increased the gene expression of the M2 macrophage marker, CD206, in the sciatic nerves of the diabetic rats. The in vitro study showed that DPSC-conditioned media significantly increased the gene expressions of interleukin-10 and CD206 in lipopolysaccharide-stimulated RAW264.7 cells. CONCLUSIONS: These results suggest that DPSC transplantation promoted macrophages polarization towards anti-inflammatory M2 phenotypes, which might be one of the therapeutic mechanisms for diabetic polyneuropathy.

Transplantation of cultured dental pulp stem cells into the skeletal muscles ameliorated diabetic polyneuropathy: therapeutic plausibility of freshly isolated and cryopreserved dental pulp stem cells.

INTRODUCTION: Dental pulp stem cells (DPSCs) are mesenchymal stem cells located in dental pulp and are thought to be a potential source for cell therapy since DPSCs can be easily obtained from teeth extracted for orthodontic reasons. Obtained DPSCs can be cryopreserved until necessary and thawed and expanded when needed. The aim of this study is to evaluate the therapeutic potential of DPSC transplantation for diabetic polyneuropathy. METHODS: DPSCs isolated from the dental pulp of extracted incisors of Sprague-Dawley rats were partly frozen in a -80 °C freezer for 6 months. Cultured DPSCs were transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocine injection and the effects of DPSC transplantation were evaluated 4 weeks after the transplantation. RESULTS: Transplantation of DPSCs significantly improved the impaired sciatic nerve blood flow, sciatic motor/sensory nerve conduction velocity, capillary number to muscle fiber ratio and intra-epidermal nerve fiber density in the transplanted side of diabetic rats. Cryopreservation of DPSCs did not impair their proliferative or differential ability. The transplantation of cryopreserved DPSCs ameliorated sciatic nerve blood flow and sciatic nerve conduction velocity as well as freshly isolated DPSCs. CONCLUSIONS: We demonstrated the effectiveness of DPSC transplantation for diabetic polyneuropathy even when using cryopreserved DPSCs, suggesting that the transplantation of DPSCs could be a promising tool for the treatment of diabetic neuropathy.

The pattern of tongue pressure against the palate during articulating glossal sounds in normal subjects and glossectomy patients.

The purpose of the present study was to measure tongue pressure with the aim of characterizing the pattern of linguopalatal contact during articulating glossal sounds in normal subjects and glossectomy patients. Tongue pressures against the palate were evaluated in 13 normal subjects and 5 glossectomy patients by using three parameters: the duration from the onset of linguopalatal contact to the time of maximum pressure, the maximum pressure, and anterior posterior ratio of the maximum pressure. Three glossal sounds, [ti], [t [symbol: see text] i], and [[symbol: see text] i], which have tendency of mishearing in glossectomy patients, were selected for test sounds. A unique characteristic was demonstrated in normal subjects. The score of the maximum pressure showed an apparent order among the three sounds, while the durations revealed the opposite order. Anterior posterior ratio of the maximum pressure also showed some relationship among three sounds. In glossectomy patients, these characters were not found. The loss of tongue volume or deterioration of tongue mobility causes these results.

Vibration analysis of obturator prostheses with different bulb height designs.

The purpose of this study was to investigate the effect on the vibratory characteristics of a cast hollow obturator prosthesis retainer when varying its bulb height. Bulb parts with high (H), middle (M), and low (L) lateral walls were prepared. A Vibration Generator was used to excite the three obturators, while a Laser-Doppler Vibrometer was employed to detect the vibrations at specified measurement points. The frequency response functions of each obturator were recorded on an FFT analyzer to enable their modal shapes to be identified. In addition, transient response simulations were carried out and the decay rate (DR) and the maximum amplitude (MA) of the rest and clasp parts of each obturator were obtained. These were statistically analyzed by ANOVA and Fisher's PLSD test (p < 0.01). The modal shapes were almost the same in all obturators. Significant differences were found in DR in all pairs among the three obturator prostheses, with the DR of the L type being the highest. On the other hand, there were no significant differences in MA. We conclude that the L type is preferable from the standpoint of its vibratory characteristics.

Mechanical stretch increases the proliferation while inhibiting the osteogenic differentiation in dental pulp stem cells.

Dental pulp stem cells (DPSCs), which can differentiate into several types of cells, are subjected to mechanical stress by jaw movement and occlusal forces. In this study, we evaluated how the uniaxial mechanical stretch influences proliferation and differentiation of DPSCs. DPSCs were isolated and cultured from male Sprague-Dawley rats. Cultured DPSCs were identified by surface markers and the differentiation capabilities as adipocytes or osteoblasts. To examine the response to mechanical stress, uniaxial stretch was exposed to cultured DPSCs. We evaluated the impact of stretch on the intracellular signaling, proliferation, osteogenic differentiation, and gene expressions of DPSCs. Stretch increased the phosphorylation of Akt, ERK1/2, and p38 MAP kinase as well as the proliferation of DPSCs. The stretch-induced proliferation of DPSCs was abolished by the inhibition of the ERK pathway. On the other hand, stretch significantly decreased the osteogenic differentiation of DPSCs, but did not affect the adipogenic differentiation. We also confirmed mRNA expressions of osteocalcin and osteopontin were significantly suppressed by stretch. In conclusion, uniaxial stretch increased the proliferation of DPSCs, while suppressing osteogenic differentiation. These results suggest a crucial role of mechanical stretch in the preservation of DPSCs in dentin. Furthermore, mechanical stretch may be a useful tool for increasing the quantity of DPSCs in vitro for regenerative medicine.

An experimental study of bone grafting using rat milled tooth.

PURPOSE: The aim of this study was to develop a novel bone graft material that used extracted teeth. MATERIALS AND METHODS: Thirty-six 10-week-old male Wistar rats were used. The incisors were extracted, immediately frozen and milled, mixed with hydroxypropyl cellulose (HPC), and injected into the socket. The remaining rats received HPC alone, or the socket was left to heal untreated. Socket healing and bone formation in all three groups were evaluated by three-dimensional image analysis from microcomputed tomography examination and histologic observation. RESULTS: Quantitative morphologic measurements demonstrated that bone formation was significantly stimulated in the group that received milled tooth and HPC at 2 and 4 weeks after extraction compared to that of the control (untreated) group, which showed normal healing without any intervention. Histologic observation revealed that the compound of milled tooth and HPC promoted early healing of the socket and initiation of bone formation in the surrounding area. Interestingly, HPC injection alone decreased bone formation and bone mineral content at 2 weeks and then increased bone formation at 4 weeks. CONCLUSION: A bone graft material composed of milled tooth promotes early healing and bone formation, while HPC, which is chemically stable in vivo, affects bone formation in the extraction socket.

High-throughput gene expression analysis in bone healing around titanium implants by DNA microarray.

OBJECTIVE: Bone generation occurs around titanium implants; however, its underlying mechanisms are relatively unknown. We attempt to identify gene transcripts specifically upregulated in in vivo bone healing with titanium implants using DNA microarray. MATERIAL AND METHODS: Titanium implants were placed into rat femurs, and total RNA was extracted from the implant-associated tissue at weeks 1, 2 and 4 of healing. As a control, RNA was extracted from the tissue undergoing osteotomy healing. The RNA samples were hybridized onto oligo DNA microarray. RESULTS: Most of the 20,000 genes tested were expressed similarly in both the implant- and osteotomy-healing groups. Eighty-six genes were upregulated (>2-fold) in the implant-healing group compared with the osteotomy-healing group in at least one time point of healing. Twelve genes were upregulated in the implant healing at week 2 and earlier, while 31 genes were upregulated at week 2 and later. Only one gene was upregulated specifically at week 1, while three genes were consistently upregulated from weeks 1 to 4. The upregulated genes included collagenous and non-collagenous extracellular matrix (ECM)-related genes, proteoglycans and bone resorption-related genes. Pathway analysis revealed the involvement of ECM and receptor interaction in implant healing. CONCLUSIONS: This study provides evidence that a set of gene transcripts is upregulated in the implant healing over the osteotomy healing, which seems to represent the coordinated biological events of long-lasting osteogenesis and bone remodeling required for osseointegration. Further studies are needed to identify the significance and biological roles of the transcripts in osseointegration. Proven reliability and usefulness of microarray technology should encourage future approaches to develop a high-throughput molecular assessment for osseointegration capacity of new implant surfaces.

A maxillary lip prosthesis retained by an obturator with attachments: A clinical report.

This article describes the prosthetic rehabilitation of small maxillary lip and maxilla defects with a lip prosthesis attached to an obturator. The definitive obturator prosthesis was designed with 3 plastic ball attachments on the labial surface that provided adequate retention for the lip prosthesis. The thin margin of the lip prosthesis ensured that it adapted well to functional movements.

Photoelastic stress analysis of implant-tooth connected prostheses with segmented and nonsegmented abutments.

STATEMENT OF PROBLEM: There is some question about whether implant abutment selection affects the transfer of load between connected implants and natural teeth. PURPOSE: The purpose of this study was to compare stress transfer patterns with either 1 or 2 posterior implants connected to a single anteriorly located simulated natural tooth with either 1 or 2 segmented and nonsegmented implant abutments under relevant functional loads by use of the photoelastic stress analysis technique. MATERIAL AND METHODS: A model of a human left mandible, edentulous posterior to the first premolar, with two 3.75-mm x 13-mm screw-type implants embedded within the edentulous area, was fabricated from photoelastic materials. The implants were in the first and second molar positions. Two fixed partial denture prosthetic restorations were fabricated with either segmented conical abutments or nonsegmented UCLA abutments. Vertical occlusal loads were applied at fixed locations on the restorations. The photoelastic stress fringes that developed in the supporting mandible were monitored visually and recorded photographically. The stress intensity (number of fringes), stress concentrations (closeness of fringes), and their locations were subjectively compared. RESULTS: Loading on the restoration over the simulated tooth generated apical stresses of similar intensity (fringe order) at the tooth and the first molar implant for both abutment types. Low-level stress was transferred to the second molar implant. Loading directed on the implant-supported region of the restoration demonstrated low transfer of stress to the simulated tooth. Nonvertical stress transfer with slightly higher intensity was observed for the nonsegmented abutment. CONCLUSION: Within the limitations of this simulation study, stress distribution and intensity for the 2 implant conditions was similar for segmented and nonsegmented abutment designs. Magnitude of stresses observed for both abutment designs was similar for the single implant condition. Vertical loading produced more nonaxial stresses away from the force applied for the 1 implant condition with the nonsegmented abutment. Direct loading results were similar for both abutment designs. Specific recommendations for selection of implant abutment and application should be based on clinical criteria.