The standard procedure for the osteogenic differentiation of multipotent stem cells is treatment of a confluent monolayer with a cocktail of dexamethasone (Dex), ascorbic acid (Asc) and β-glycerophosphate (β-Gly). This review describes the effects of these substances on intracellular signaling cascades that lead to osteogenic differentiation of bone marrow stroma-derived stem cells. We conclude that Dex induces Runx2 expression by FHL2/β-catenin-mediated transcriptional activation and that Dex enhances Runx2 activity by upregulation of TAZ and MKP1. Asc leads to the increased secretion of collagen type I (Col1), which in turn leads to increased Col1/α2β1 integrin-mediated intracellular signaling. The phosphate from β-Gly serves as a source for the phosphate in hydroxylapatite and in addition influences intracellular signaling molecules. In this context we give special attention to the differences between dystrophic and bone-specific mineralization.
A growing number of studies have reported that mini-implants do not remain in exactly the same position during treatment, although they remain stable. The aim of this review was to collect data regarding primary displacement immediately straight after loading and secondary displacement over time. A systematic review was performed to investigate primary and secondary displacement. The amount and type of displacement were recorded. A total of 27 studies were included. Sixteen in vitro studies or studies using finite element analysis addressed primary displacement, and nine clinical studies and two animal studies addressed secondary displacement. Significant primary displacement was detected (6.4–24.4 µm) for relevant orthodontic forces (0.5–2.5 N). The mean secondary displacement ranged from 0 to 2.7 mm for entire mini-implants. The maximum values for each clinical study ranged from 1.0 to 4.1 mm for the head, 1.0 to 1.5 for the body and 1.0 to 1.92 mm for the tail part. The most frequent type of movement was controlled tipping or bodily movement. Primary displacement did not reach a clinically significant level. However, clinicians can expect relevant secondary displacement in the direction of force. Consequently, decentralized insertion within the inter-radicular space, away from force direction, might be favourable. More evidence is needed to provide quantitative recommendations.
displacement; migration; mini-implant; miniscrew; orthodontics; skeletal anchorage
This study was conducted to verify the results of a preceding retrospective pilot study by means of a prospective controlled investigation including a larger sample size. Therefore, the aim of this clinical investigation was to analyze the relationship between sleep bruxism and several functional and occlusal parameters. The null hypothesis of this study was that there would be no differences among sleep bruxism subjects and non-sleep bruxism controls regarding several functional and occlusal parameters. Fifty-eight sleep bruxism subjects and 31 controls participated in this study. The diagnosis sleep bruxism was based on clinical criteria of the American Academy of Sleep Medicine. Sixteen functional and occlusal parameters were recorded clinically or from dental study casts. Similar to the recently published retrospective pilot study, with a mean slide of 0.77 mm (s.d., 0.69 mm) in the sleep bruxism group and a mean slide of 0.4 mm (s.d., 0.57 mm) in the control group, the evaluation of the mean comparison between the two groups demonstrated a larger slide from centric occlusion to maximum intercuspation in sleep bruxism subjects (Mann–Whitney U-test; P=0.008). However, following Bonferroni adjustment, none of the 16 occlusal and functional variables differed significantly between the sleep bruxism subjects and the non-sleep bruxism controls. The present study shows that the occlusal and functional parameters evaluated do not differ between sleep bruxism subjects and non-sleep bruxism subjects. However, as the literature reveals a possible association between bruxism and certain subgroups of temporomandibular disorders, it appears advisable to incorporate the individual adaptive capacity of the stomatognathic system into future investigations.
dental occlusion; functional parameters; prospective study; sleep bruxism
Cystadenolymphomas (Warthin's tumors) are the second most frequent lesions of the parotid gland. Due to their benign clinical behavior, the low rates of recurrence and malignant transformation they were classified as tumor-like lesions. In addition, a polyclonal growth of the epithelial components of the tumor could be detected. Warthin's tumors occur bilateral in 7-10%, whereas a multifocal appearance is extremely rare. Even if the pathogenesis is still unclear a heterotopia of salivary tissue during embryogenesis is the most likely explanation for the origin of these tumors in the upper neck and periparotideal region. Here we present a rare case of bilateral, multifocal, extraglandular Warthin's tumors in lymph nodes of the upper neck and give a brief review of the literature. If a primary malignancy can be excluded by a careful staging procedure prior to the operation an isolated excision of the lesions of the neck is the adequate treatment.
Warthin's tumor; Bilateral; Multifocal; Neck lymph nodes; Treatment; Pathogenesis
Extracorporeal formation of mineralized bone-like tissue is still an unsolved challenge in tissue engineering. Embryonic stem cells may open up new therapeutic options for the future and should be an interesting model for the analysis of fetal organogenesis. Here we describe a technique for culturing embryonic stem cells (ESCs) in the absence of artificial scaffolds which generated mineralized miromasses. Embryonic stem cells were harvested and osteogenic differentiation was stimulated by the addition of dexamethasone, ascorbic acid, and ß-glycerolphosphate (DAG). After three days of cultivation microspheres were formed. These spherical three-dimensional cell units showed a peripheral zone consisting of densely packed cell layers surrounded by minerals that were embedded in the extracellular matrix. Alizarine red staining confirmed evidence of mineralization after 10 days of DAG stimulation in the stimulated but not in the control group. Transmission electron microscopy demonstrated scorching crystallites and collagenous fibrils as early indication of bone formation. These extracellular structures resembled hydroxyl apatite-like crystals as demonstrated by distinct diffraction patterns using electron diffraction analysis. The micromass culture technique is an appropriate model to form three-dimensional bone-like micro-units without the need for an underlying scaffold. Further studies will have to show whether the technique is applicable also to pluripotent stem cells of different origin.
Embryonal stem cell; osteogenic tissue engineering; three-dimensional culture technique; scaffold free tissue; hydroxyl apatite
Osteonecrosis after craniofacial radiation (ORN), osteomyelitis and bisphosphonates related necrosis of the jaw (BRONJ) are the predominant bone diseases in Cranio- and Maxillofacial surgery. Although various hypothesis for the pathophysiological mechanisms including infection, altered vascularisation or remodelling exist, the treatment is still a challenge for clinicians. As the classical pharmacological or surgical treatment protocols have only limited success, stem cells might be a promising treatment option, indicated by recently published data.
Late diagnosis resulting in late treatment and locoregional failure after surgery are the main causes of death in patients with oral squamous cell carcinomas (SCCs). Actually, exfoliative cytology is increasingly used for early detection of oral cancer and has been the subject of intense research over the last five years. Significant advances have been made both in relation to screening and evaluation of precursor lesions. As this noninvasive procedure is well tolerated by patients, more lesions may be screened and thus more oral cancers may be found in early, curable stages. Moreover, the additional use of DNA image cytometry is a reasonable tool for the assessment of the resection margins of SCC. DNA image cytometry could help to find the appropriate treatment option for the patients. Finally, diagnostic DNA image cytometry is an accurate method and has internationally been standardized.
In conclusion, DNA image cytometry has increasing impact on the prevention, diagnostic, and therapeutical considerations in head and neck SCC.
Desmoplastic fibroma (DF) is a rare, benign but locally aggressive, intraosseous lesion with a high tendency of local recurrence. In this report the actual literature is reviewed regarding epidemiological data, pathology, clinical diagnostic criterias, therapy and prognosis. Moreover, a report of an interesting case is included localized in the mandibular corpus.
Solitary neurofibroma is a rare benign non-odontogenic tumor. Particularly in the oral cavity, neurogenic tumors are rare, especially if they are malignant. Neurofibromas may present either as solitary lesions or as part of the generalised syndrome of neurofibromatosis or von Recklinghausen's disease of the skin. Clinically, oral neurofibromas usually appear as pediculated or sessile nodules, with slow growth and mostly without pain. The diagnosis can be confirmed by histological examination. Neurofibromas are immunopositive for the S-100 protein, indicating its neural origin. Treatment is surgical and the prognosis is excellent. For illustration a rare case of a solitary neurofibroma in the mandible is presented.
Several grafting materials have been used in sinus augmentation procedures including autogenous bone, demineralized freeze-dried bone (DFDBA), hydroxyapatite, β-tricalcium phosphate (β-TCP), anorganic deproteinized bovine bone and combination of these and others. Up to now a subject of controversy in maxillofacial surgery and dentistry is, what is the most appropriate graft material for sinus floor augmentation.
The aim of this study is to provide a body of evidence-based data regarding grafting materials in external sinus floor elevation concerning the fate of the augmented material at the histomorphological level, through a meta-analysis of the available literature.
The literature searches were performed using the National Library of Medicine. The search covered all English and German literature from 1995 until 2006. For analyzing the amount of bone the parameter "Total Bone Volume" (TBV) was assessed. TBV is determined as the percentage of the section consisting of bone tissue.
In a relatively early phase after implantation the autogenous bone shows the highest TBV values. Interestingly, the different TBV levels approximate during the time. After 9 months no statistically significant differences can be detected between the various grafting materials.
From a clinical point of view, the use of autogenous bone is advantageous if a prosthetic rehabilitation (with functional loading) is expected within 9 months. In other cases the use of anorganic deproteinized bovine bone in combination with autogenous bone seems to be preferable. Donor side morbidity is ignored in this conclusion.
Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries.
Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques.
Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed.
The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.
Osseointegration is crucial for the long-term success of dental implants and depends on the tissue reaction at the tissue-implant interface. Mechanical properties and biocompatibility make zirconia a suitable material for dental implants, although surface processings are still problematic. The aim of the present study was to compare osteoblast behavior on structured zirconia and titanium surfaces under standardized conditions.
The surface characteristics were determined by scanning electron microscopy (SEM). In primary bovine osteoblasts attachment kinetics, proliferation rate and synthesis of bone-associated proteins were tested on different surfaces.
The results demonstrated that the proliferation rate of cells was significantly higher on zirconia surfaces than on titanium surfaces (p < 0.05; Student's t-test). In contrast, attachment and adhesion strength of the primary cells was significant higher on titanium surfaces (p < 0.05; U test). No significant differences were found in the synthesis of bone-specific proteins. Ultrastructural analysis revealed phenotypic features of osteoblast-like cells on both zirconia and titanium surfaces.
The study demonstrates distinct effects of the surface composition on osteoblasts in culture. Zirconia improves cell proliferation significantly during the first days of culture, but it does not improve attachment and adhesion strength. Both materials do not differ with respect to protein synthesis or ultrastructural appearance of osteoblasts. Zirconium oxide may therefore be a suitable material for dental implants.
Reconstruction of the facial hard- and soft tissues is of special concern for the rehabilitation of patients especially after ablative tumor surgery has been performed. Impaired soft and hard tissue conditions as a sequelae of extensive surgical resection and/or radiotherapy may impede common reconstruction methodes. Even free flaps may not be used without interposition of a vein graft as recipient vessels are not available as a consequence of radical neck dissection.
We describe the reconstruction of the facial hard- and soft tissues with a free parasacpular flap in a patient who had received ablative tumor surgery and radical cervical lymphadenectomy as a treatment regimen for squamous cell carcinoma (SCC). To replace the missing cervical blood vessels an arteriovenous subclavia-shunt using a saphena magna graft was created. Microvascular free flap transfer was performed as a 2-stage procedure two weeks after the shunt operation. The microvascular reconstructive technique is described in detail.
The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level.
A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Göttinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface.
Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography.
The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.
Psychological factors are not only important in patients with temporomandibular disorders (TMDs), but also in patients suffering from tooth loss and/or in those awaiting prosthodontic care with fixed or removable dentures as several authors emphasize. The purpose of the present prospective observational study was to compare prosthodontic outpatients of the Department of Prosthodontics at the University of Duesseldorf and patients seeking care at the TMD/Orofacial Pain Outpatient Clinic (TMD/OFPOC) at the same university with respect to sociodemographic data, self-reported somatic complaints, and psychological impairment.
A total of 234 patients received two self-administered questionnaires including the Symptom-Check-List. Complete data have been obtained from 65 prosthodontic outpatients and 60 patients of the TMD/OFPOC.
Results indicated statistically significant group differences regarding sociodemographic data and somatic complaints. Concerning the latter, in 11 of the 21 items, groups differed significantly and confirmed the absence of any mixing between the two outpatient clinics. Although the evaluation of psychological impairment revealed no significant group differences, in 21.9% of the prosthodontic outpatients and in 22.0% of the patients from the TMD/OFPOC, the extent of the determined psychological impairment was similar to that of psychotherapeutic outpatients; in 9.4% and 8.5% it was similar to that of psychotherapeutic inpatients, respectively.
Within the limitations of this study, in approximately one third of the evaluated patients of both the prosthodontic outpatient clinic and the TMD/OFPOC the psychological impairment reached values comparable to those of psychotherapeutic outpatients and psychotherapeutic inpatients. Therefore, the present findings emphasize the need to intensify the integration of psychosomatic aspects into dentistry and, in particular, to add psychological considerations to future German education plans.
Facial trauma or tumor surgery in the head and face area often lead to massive destruction of the facial skeleton. Cell-based bone reconstruction therapies promise to offer new therapeutic opportunities for the repair of bone damaged by disease or injury. Currently, embryonic stem cells (ESCs) are discussed to be a potential cell source for bone tissue engineering. The purpose of this study was to investigate various supplements in culture media with respect to the induction of osteogenic differentiation.
Murine ESCs were cultured in the presence of LIF (leukemia inhibitory factor), DAG (dexamethasone, ascorbic acid and β-glycerophosphate) or bone morphogenetic protein-2 (BMP-2). Microscopical analyses were performed using von Kossa staining, and expression of osteogenic marker genes was determined by real time PCR.
ESCs cultured with DAG showed by far the largest deposition of calcium phosphate-containing minerals. Starting at day 9 of culture, a strong increase in collagen I mRNA expression was detected in the DAG-treated cells. In BMP-2-treated ESCs the collagen I mRNA induction was less increased. Expression of osteocalcin, a highly specific marker for osteogentic differentiation, showed a double-peaked curve in DAG-treated cells. ESCs cultured in the presence of DAG showed a strong increase in osteocalcin mRNA at day 9 followed by a second peak starting at day 17.
Supplementation of ESC cell cultures with DAG is effective in inducing osteogenic differentiation and appears to be more potent than stimulation with BMP-2 alone. Thus, DAG treatment can be recommended for generating ESC populations with osteogenic differentiation that are intended for use in bone tissue engineering.
Diseases and defects of the temporomandibular joint (TMJ), compromising the cartilaginous layer of the condyle, impose a significant treatment challenge. Different regeneration approaches, especially surgical interventions at the TMJ's cartilage surface, are established treatment methods in maxillofacial surgery but fail to induce a regeneration ad integrum. Cartilage tissue engineering, in contrast, is a newly introduced treatment option in cartilage reconstruction strategies aimed to heal cartilaginous defects. Because cartilage has a limited capacity for intrinsic repair, and even minor lesions or injuries may lead to progressive damage, biological oriented approaches have gained special interest in cartilage therapy. Cell based cartilage regeneration is suggested to improve cartilage repair or reconstruction therapies. Autologous cell implantation, for example, is the first step as a clinically used cell based regeneration option. More advanced or complex therapeutical options (extracorporeal cartilage engineering, genetic engineering, both under evaluation in pre-clinical investigations) have not reached the level of clinical trials but may be approached in the near future. In order to understand cartilage tissue engineering as a new treatment option, an overview of the biological, engineering, and clinical challenges as well as the inherent constraints of the different treatment modalities are given in this paper.
Dentin dysplasia type I is characterized by a defect of dentin development with clinical normal appearance of the permanent teeth but no or only rudimentary root formation. Early loss of all teeth and concomitant underdevelopment of the jaws are challenging for successful treatment with dental implants.
A combination of sinus lifting and onlay bone augmentation based on treatment planning using stereolithographic templates was used in a patient with dentin dysplasia type I to rehabilitate the masticatory function.
(i) a predisposition for an increased and accelerated bone resorption was observed in our patient, (ii) bone augmentation was successful using a mixture of allogenic graft material with autogenous bone preventing fast bone resorption, (iii) surgical planning, based on stereolithographic models and surgical templates, facilitated the accurate placement of dental implants.
Bony augmentation and elaborate treatment planning is helpful for oral rehabilitation of patients with dentin dysplasia type I.
Tissue engineering of bone and cartilage tissue for subsequent implantation is of growing interest in cranio- and maxillofacial surgery. Commonly it is performed by using cells coaxed with scaffolds. Recently, there is a controversy concerning the use of artificial scaffolds compared to the use of a natural matrix. Therefore, new approaches called micromass technology have been invented to overcome these problems by avoiding the need for scaffolds. Technically, cells are dissociated and the dispersed cells are then reaggregated into cellular spheres. The micromass technology approach enables investigators to follow tissue formation from single cell sources to organised spheres in a controlled environment. Thus, the inherent fundamentals of tissue engineering are better revealed. Additionally, as the newly formed tissue is devoid of an artificial material, it resembles more closely the in vivo situation. The purpose of this review is to provide an insight into the fundamentals and the technique of micromass cell culture used to study bone tissue engineering.
Functional rehabilitation of patients afflicted with severe mandibular and maxillary alveolar atrophy might be challenging especially in malformed patients.
Treatment planning using sinus lifting and implant placement before Le Fort I maxillary osteotomy in a patient with severe mandibular and posterior maxillary alveolar atrophy and skelettal class-III conditions due to cleft palate are described.
A full functional and esthetic rehabilitation of the patient was achieved by a stepwise surgical approach performed through sinus lifting as the primary approach followed by implant placement and subsequent Le Fort I maxillary osteotomy to correct the maxillo-mandibular relation.
Stabilisation of the maxillary complex by a sinus lifting procedure in combination with computer aided implant placement as preorthodontic planning procedure before Le Fort I maxillary osteotomy seems to be suitable in order to allow ideal oral rehabilitation especially in malformed patients.
Adenomatoid odontogenic tumor (AOT) is a rare odontogenic tumor which is often misdiagnosed as odontogenic cyst. To acquire additional information about AOT, all reports regarding AOT and cited in "pubmed" since 1990 onward were reviewed. AOT accounts for about 1% until 9% of all odontogenic tumors. It is predominantly found in young and female patients, located more often in the maxilla in most cases associated with an uneruppted permanent tooth. For radiological diagnose the intraoral periapical radiograph seems to be more useful than panoramic. However, AOT frequently resemble other odontogenic lesions such as dentigerous cysts or ameloblastoma. Immunohistochemically AOT is characterized by positive reactions with certain cytokeratins. Treatment is conservative and the prognosis is excellent. For illustration a rare case of an AOT in the mandible is presented.
adenomatoid odontogenic tumor; review