Ralf Smeets

Publications of Ralf Smeets

• Current trends and future perspectives of bone substitute materials - From space holders to innovative biomaterials.

  Authors: Andreas Kolk, Jörg Handschel, Wolf Drescher, Daniel Rothamel, Frank Kloss, Marco Blessmann, Max Heiland, Klaus-Dietrich Wolff, Ralf Smeets

  Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 01/2012;

  An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacementAn autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging.

• Effect of oxidized regenerated cellulose/collagen matrix on proteases in wound exudate of patients with diabetic foot ulcers.

  Authors: Dietmar Ulrich, Ralf Smeets, Frank Unglaub, Michael Wöltje, Norbert Pallua

  Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society / WOCN. 08/2011; 38(5):522-8.

  The aim of this study was to investigate the influence of oxidized regenerated cellulose/collagen matrix on the concentration and activity of gelatinases, elastase, and plasmin in wound exudate. TheThe aim of this study was to investigate the influence of oxidized regenerated cellulose/collagen matrix on the concentration and activity of gelatinases, elastase, and plasmin in wound exudate. The study included 32 patients with diabetic foot ulcers. Ten patients with a mean age of 66 ± 9 years (mean ± SD) were treated with hydrocolloid dressings; 22 patients with a mean age of 57 ± 12 years were treated with oxidized regenerated/collagen matrix and hydrocolloid dressings. Wound exudate was collected on days 0, 5, 14, and every 14 days thereafter for 12 weeks. Total protein was determined according to Bradford's technique. The levels of elastase and plasmin were measured spectrofluorometrically. Besides, gelatinase activity and matrix metalloproteinase-2 concentration were analyzed. The surface area of all ulcers was measured by planimetry. Patients treated with oxidized regenerated cellulose/collagen matrix showed a significant decrease in elastase, plasmin, and gelatinase activities in wound exudates. The matrix metalloproteinase-2 concentration was significantly reduced on days 14, 28, 42, and 56 in comparison to day 0. Furthermore, wound size was significantly reduced at days 14 and 28 in oxidized regenerated cellulose/collagen matrix-treated patients (P < .05). Our results showed a significant and immediate reduction in the levels of all tested proteases in the wound exudate of diabetic foot ulcer patients treated with oxidized regenerated cellulose/collagen matrix. These patients also experienced a significantly greater reduction in wound size.

• Adhesion molecule L1 is down-regulated in malignant peripheral nerve sheath tumors versus benign neurofibromatosis type 1-associated tumors.

  Authors: Marco Blessmann, Alexander Gröbe, Alexander Quaas, Jussuf T Kaifi, Georgios Mistakidis, Christian Bernreuther, Guido Sauter, Stephanie Gros, Tamina Rawnaq, Reinhard Friedrich, Victor F Mautner, Ralf Smeets, Max Heiland, Melitta Schachner, Jakob R Izbicki

  Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 08/2011;

  Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is caused by a disorder of a single gene on chromosome 17 that usually restrains cell division. A sequence that isType 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is caused by a disorder of a single gene on chromosome 17 that usually restrains cell division. A sequence that is frequently associated with NF-1 is tumor progression from neurofibromas to malignant peripheral nerve sheath tumors (MPNSTs). The aim of this study was to determine the expression of the neural L1 cell adhesion molecule in dermal-diffuse neurofibromas, plexiform neurofibromas, and MPNSTs of NF-1. We retrospectively analyzed surgically resected primary tumors, including 20 dermal neurofibromas, 23 plexiform neurofibromas, and 17 MPNSTs, by immunohistochemistry in paraffin sections of NF-1 tumors with the use of the L1-specific monoclonal antibody UJ127, which does not cross-react with other members of the L1 family. Immunostainings for CD34 and S100 were included to distinguish and allocate L1-expressing Schwann cells and perineural (specialized) fibroblasts. Our data showed that L1 is highly expressed in all benign NF-1 tumors and in some but not all MPNSTs. Furthermore, we demonstrated a correlation between L1 expression and differentiation grade of MPNSTs. There was a significant trend toward lower or nondetectable expression in the poorly differentiated MPNSTs, in contrast to all other tumor entities so far investigated, in which L1 expression correlated positive with malignancy, except for juvenile but not adult-derived neuroblastomas. Future studies are warranted to elucidate the molecular basis of the varying effects of the degree of L1 expression, receptor, and signal transduction mechanisms in different tumors.

• Verification of nerve integrity after surgical intervention using quantitative sensory testing.

  Authors: Sareh Said-Yekta, Ralf Smeets, Marcella Esteves-Oliveira, Jamal M Stein, Dieter Riediger, Friedrich Lampert

  Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 07/2011; 70(2):263-71.

  The aim of this study was to apply a standardized Quantitative Sensory Testing (QST) approach in patients to investigate whether oral surgery can lead to sensory changes, even if the patients do notThe aim of this study was to apply a standardized Quantitative Sensory Testing (QST) approach in patients to investigate whether oral surgery can lead to sensory changes, even if the patients do not report any sensory disturbances. Furthermore, this study determines the degree and duration of possible neuronal hyperexcitability due to local inflammatory trauma after oral surgery. Orofacial sensory functions were investigated by psychophysical means in 60 patients (30 male, 30 female) in innervation areas of infraorbital nerves, mental nerves and lingual nerves after different interventions in oral surgery. The patients were tested 1 week, 4 weeks, 7 weeks, and 10 weeks postoperatively. As controls for bilateral sensory changes after unilateral surgery, tests were additionally performed in 20 volunteers who did not have any dental restorations. No differences were found between the control group and the control side of the patients. Although not 1 of the patients reported paresthesia or other sensory changes postoperatively, QST detected significant differences between the control and the test side in the mental and lingual regions. Test sides were significantly less sensitive for thermal parameters (cold, warm, and heat). No differences were found in the infraorbital region. Patients showed significantly decreased pain pressure thresholds on the operated side. QST monitored recovery over time in all patients. The results show that oral surgery can lead to sensory deficits in the mental and lingual region, even if the patients do not notice any sensory disturbances. The applied QST battery is a useful tool to investigate trigeminal nerve function in the early postoperative period. In light of the increasing forensic implication, this tool can serve to objectify clinical findings.

• Manufacturing of individual biodegradable bone substitute implants using selective laser melting technique.

  Authors: Markus Lindner, Simon Hoeges, Wilhelm Meiners, Konrad Wissenbach, Ralf Smeets, Rainer Telle, Reinhart Poprawe, Horst Fischer

  Journal of biomedical materials research. Part A. 06/2011; 97(4):466-71.

  The additive manufacturing technique selective laser melting (SLM) has been successfully proved to be suitable for applications in implant manufacturing. SLM is well known for metal parts and offersThe additive manufacturing technique selective laser melting (SLM) has been successfully proved to be suitable for applications in implant manufacturing. SLM is well known for metal parts and offers direct manufacturing of three-dimensional (3D) parts with high bulk density on the base of individual 3D data, including computer tomography models of anatomical structures. Furthermore, an interconnecting porous structure with defined and reproducible pore size can be integrated during the design of the 3D virtual model of the implant. The objective of this study was to develop the SLM processes for a biodegradable composite material made of β-tricalcium phosphate (β-TCP) and poly(D, L)-lactide (PDLLA). The development of a powder composite material (β-TCP/PDLLA) suitable for the SLM process was successfully performed. The microstructure of the manufactured samples exhibit a homogeneous arrangement of ceramic and polymer. The four-point bending strength was up to 23 MPa. The X-ray diffraction (XRD) analysis of the samples confirmed β-TCP as the only present crystalline phase and the gel permeations chromatography (GPC) analysis documented a degradation of the polymer caused by the laser process less than conventional manufacturing processes. We conclude that SLM presents a new possibility to manufacture individual biodegradable implants made of β-TCP/PDLLA.

• The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro.

  Authors: Felix P Koch, Annette Wunsch, Christina Merkel, Thomas Ziebart, Andreas Pabst, Sareh Said Yekta, Marco Blessmann, Ralf Smeets

  Head & face medicine. 02/2011; 7(1):4.

  Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jawBisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10(-5)M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5 data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control. After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels. Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.

• A novel hemostatic delivery device for thrombin: biodegradable poly(D,L-lactide-co-glycolide) 50:50 microspheres.

  Authors: Ralf Smeets, Frank Gerhards, Jamal M Stein, Jamal Stein, Rui Miguel Pereira Paz, Stephan Vogt, Christoph Pautke, Jochen Weitz, Andreas Kolk

  Journal of biomedical materials research. Part A. 01/2011; 96(1):177-85.

  Topical thrombins are locally active hemostatic agents that can be used to minimize blood loss during any surgery. The aim of this study was to design and investigate a thrombin-containingTopical thrombins are locally active hemostatic agents that can be used to minimize blood loss during any surgery. The aim of this study was to design and investigate a thrombin-containing biodegradable hemostyptic device with an optimized drug release profile to promote local blood clot formation. It is effective with ongoing systemic antithrombotic therapy and can be used in all types of bone-related surgery, for example, in dental surgery. Thrombin-loaded poly(D,L-lactide-co-glycolide) microspheres were synthesized by means of complex (w/o/w) emulsion evaporation method. The resulting enzyme activity of the serine-protease thrombin was verified by the specific chromogenic substrate S-2238. The thrombin release profile depended on four factors: (1) thrombin dosage, (2) polymer concentration in the o-phase, (3) phase quotient w1:0 in the primary emulsion, and (4) the addition of pore-introducing agents. A collagenous sponge containing thrombin-loaded microspheres by means of lyophilization was developed. The impact of several production factors of the (w1/o/w2) solvent evaporation method to optimize thrombin encapsulation, morphology of the spheres, and desired drug release profile have been investigated. The in vitro thrombin release was dependent on the polymer-to-oil phase ratio, the polymer concentration, and the type of solvent and polymer. The porosity of the spheres and release rate of the active agent were enhanced by increasing the inner aqueous w1 phase. With this study, a new biodegradable hemostyptic device could be verified and established for a potentially safe and locally controlled thrombin release to manage postsurgical hemorrhage in patients undergoing anticoagulant therapy.

• Assessment of trigeminal nerve functions by quantitative sensory testing in patients and healthy volunteers.

  Authors: Sareh Said Yekta, Ralf Smeets, Jamal M Stein, Jens Ellrich

  Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 10/2010; 68(10):2437-51.

  Orofacial sensory dysfunction plays an important role in oral and maxillofacial surgery. Quantitative sensory testing (QST) is a psychophysical approach to evaluate thermal and mechanicalOrofacial sensory dysfunction plays an important role in oral and maxillofacial surgery. Quantitative sensory testing (QST) is a psychophysical approach to evaluate thermal and mechanical somatosensation. The present human study 1) collected normative QST data in extraoral and intraoral regions, 2) analyzed effects of age, gender, and anatomical sites on QST, and 3) applied QST in 11 patients with iatrogenic inferior alveolar nerve lesions. Sixty (30 male and 30 female) healthy volunteers were tested bilaterally in the innervation areas of infraorbital, mental, and lingual nerves. Ten patients with sensory disturbances in innervation areas of the mental nerve were investigated at 1, 4, and 8 weeks after surgery. Another patient with a complete sensory loss after surgery was repetitively tested within 453 days after primary surgery (dental implant) and subsequent surgical reconstruction of the inferior alveolar nerve by autologous graft. Older subjects were significantly less sensitive than younger subjects for thermal parameters. Thermal detection thresholds in infraorbital and mental regions showed higher sensitivity in women. Sensitivity to thermal stimulation was higher in the infraorbital region than in the mental and lingual regions. QST monitored somatosensory deficits and recovery of inferior alveolar nerve functions in all patients. Age, gender, and anatomic region affect various QST parameters. QST might be useful in the diagnosis of inferior alveolar nerve disorders in patients. In dentistry, the monitoring of afferent nerve fiber functions by QST might support decisions on further interventions.

• Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro.

  Authors: Felix Peter Koch, Christina Merkel, Thomas Ziebart, Ralf Smeets, Christian Walter, Bilal Al-Nawas

  Clinical oral investigations. 10/2010; 16(1):79-86.

  Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are widely known to be associated with osteonecrosis of theBisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are widely known to be associated with osteonecrosis of the jaw (BONJ). The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Nitrogen-containing and non-nitrogen containing bisphosphonates have been compared. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5 × 10(-5) M, 5 × 10(-6) M, and 5 × 10(-7) M over the experimental period of 14 days. Furthermore, the hOB cell lines were stimulated by clodronate at concentrations of 5 × 10(-3) M, 5 × 10(-5) M, and 5 × 10(-6) M. At each point in time, the gene expression levels of RANKL and OPG were quantified by real-time RT-PCR. The results showed a moderate enhancement of OPG gene expression whereas RANKL gene expression was strongly increased by nitrogen-containing bisphosphonates reaching a maximum after 14 days at high concentrations of 5 × 10(-5) M. Lower concentrations did not enhance the RANKL and OPG expression considerably. The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 × 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Interestingly, clodronate might have little influence on osteoblast/osteoclast interaction with respect to OPG and RANKL gene expression.

• In vitro study of adhesive polymethylmethacrylate bone cement bonding to cortical bone in maxillofacial surgery.

  Authors: Ralf Smeets, Rudolf Marx, Andreas Kolk, Sareh Said-Yekta, Maurice B Grosjean, Christian Stoll, Joachim Tinschert, Dieter C Wirtz, Dieter Riediger, Kira Endres

  Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 10/2010; 68(12):3028-33.

  In the treatment of midface fractures, the fragments are immobilized using screws and plates for osteosynthesis until reunion has occurred. This method involves drilling holes for the insertion ofIn the treatment of midface fractures, the fragments are immobilized using screws and plates for osteosynthesis until reunion has occurred. This method involves drilling holes for the insertion of the screws, which can be associated with additional fracturing of the corresponding bone owing to the complex architecture and thin layers of facial bone. To alleviate this problem, new adhesive techniques for fixing the plates for osteosynthesis have been investigated, mitigating the detrimental effects of screw hole drilling. In the present experimental study, the strength of this adhesive bond and its resistance to hydrolysis were investigated. To determine the adhesive bonding strength, a tension test was implemented. Osteosynthesis plates with screw holes 1.3 mm in diameter were fixed to cortical bone samples of bovine femur using ultraviolet (UV) light-curing polymethylmethacrylate bone cement. To facilitate bonding, the surface of the bone was conditioned with an amphiphilic bonding agent before cementing. UV light curing was implemented using either a conventional UV unit, such as is used in dentistry, or with a specialized UV unit with a limited emission spectrum but high luminosity. Reference control samples were prepared without application of the bone bonding agent. After this procedure, the samples were stored for 1 to 7 days at 37°C submerged in 0.9% saline solution before being subjected to the tension test. Without the bone bonding agent, the bonding strength was 0.2 MPa. The primary average bonding strength at day 0 was 8.5 MPa when cured with the conventional UV unit and 14 MPa for the samples cured with the specialized UV unit. An almost constant average bond strength of 8 and 16 MPa was noted for all samples stored up to 7 days after curing with the conventional and specialized UV unit, respectively. With the development of a new bone bonding agent, a method is now available to promote the bonding between the hydrophilic bone surface and the hydrophobic polymethylmethacrylate bone cement by creating an interlayer that is beneficial for adhesion. In the present in vitro study, the strength of this bond and its resistance to hydrolysis were investigated. This new method could have clinical bearing in cases in which conventional fixation with screws and plates is limited, such as can occur in comminuted fractures. The observed average bonding strengths of 8 to 16 MPa support the implementation of this technique in nonload-bearing regions such as the midface, facilitating immobilization until the bone reunion is complete.

• Analysis of trigeminal nerve disorders after oral and maxillofacial intervention.

  Authors: Sareh Said Yekta, Felix Koch, Maurice B Grosjean, Marcella Esteves-Oliveira, Jamal M Stein, Alireza Ghassemi, Dieter Riediger, Friedrich Lampert, Ralf Smeets

  Head & face medicine. 10/2010; 6:24.

  Quantitative sensory testing (QST) is applied to evaluate somatosensory nerve fiber function in the spinal system. This study uses QST in patients with sensory dysfunctions after oral andQuantitative sensory testing (QST) is applied to evaluate somatosensory nerve fiber function in the spinal system. This study uses QST in patients with sensory dysfunctions after oral and maxillofacial surgery. Orofacial sensory functions were investigated by psychophysical means in 60 volunteers (30 patients with sensory disturbances and 30 control subjects) in innervation areas of the infraorbital, mental and lingual nerves. The patients were tested 1 week, 4 weeks, 7 weeks and 10 weeks following oral and maxillofacial surgery. QST monitored somatosensory deficits and recovery of trigeminal nerve functions in all patients. Significant differences (p < 0.05) between control group and patients were shown for cold, warm and mechanical detection thresholds and for cold, heat and mechanical pain thresholds. Additionally, QST monitored recovery of nerve functions in all patients. QST can be applied for non-invasive assessment of sensory nerve function (Aβ-, Aδ- and C-fiber) in the orofacial region and is useful in the diagnosis of trigeminal nerve disorders in patients.

• Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner--a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2.

  Authors: Felix Peter Koch, Christina Merkel, Bilal Al-Nawas, Ralf Smeets, Thomas Ziebart, Christian Walter, Wilfried Wagner

  Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 10/2010; 39(8):562-9.

  Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jawBisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5×10(-5) M, 5×10(-6) M and 5×10(-7) M over the experimental periods of 1, 2, 5, 10 and 14 days. Clodronate was applied with concentrations of 5×10(-3), 5×10(-5) M and 5×10(-6) M. At each time point, the cells were dissolved, the mRNA extracted, and the gene expression level of the osteoblast specific differentiation markers of the homeobox transcription factors MSX1 and MSX2, the distal-less homeobox 5 (Dlx5), the Runt-related transcription factor 2 (Runx2/CBF1a) and osteocalcin (OCN) were quantified by Real-Time PCR. The gene expression was compared to an unstimulated osteoblast cell culture as control. The results showed a significant difference between the nitrogen-containing and the non-nitrogen-containing bisphosphonates. Zoledronate and ibandronate at concentrations of 5×10(-5) M enhanced the gene expression of all differentiation markers by several hundred folds compared to unstimulated control after 10 days, whereas clodronate had less influence on gene expression, even at higher concentrations of 5×10(-3) M. Lower concentrations of zoledronate and ibandronate, however, led to a decreased gene expression. These data confirm the results of other studies which have shown the osteogenic stimulus on osteoblasts in a dose dependent manner. The nitrogen-containing bisphosphonates appear to enhance bone density by stimulation of osteoblast differentiation. Non-nitrogen-containing bisphosphonates seem to have less influence on osteoblast differentiation.

• The impact of nonautogenous bone graft on orthodontic treatment.

  Authors: Christoph Reichert, Werner Götz, Ralf Smeets, Mathias Wenghöfer, Andreas Jäger

  Quintessence international (Berlin, Germany : 1985). 09/2010; 41(8):665-72.

  Guided bone regeneration with alloplastic bone graft substitutes has a high impact in surgical dentistry nowadays. In the future, the orthodontist will inevitably be confronted with patients withGuided bone regeneration with alloplastic bone graft substitutes has a high impact in surgical dentistry nowadays. In the future, the orthodontist will inevitably be confronted with patients with such a medical history. A review of the literature was performed to investigate present materials used, indications, and concerns and problems in interdisciplinary treatment of patients with nonautogenous bone grafts. An electronic key word search in the literature database PubMed of the US National Library of Medicine and The Cochrane Library (CENTRAL) of the Cochrane Collaboration was performed. Numerous journals were searched manually, and the reference lists of all identified papers related to the topic were reviewed to warrant completeness. All abstracts of the identified publications were screened in duplicate by two autonomous reviewers. Inclusion criteria were the use of a nonautogenous bone graft followed by orthodontic tooth movement or a tooth eruption through the grafting material. The total number of identified publications was 37. It was possible to divide these into two major topics, orthodontic tooth movement in bone graft and tooth eruption through bone graft. Besides experimental setups, indications were periodontal defects, cystic lesions, and alveolar clefts. Here, different types of bone graft were used. The following tooth movement was partially uneventful and sometimes attended by serious adverse effects. The resulting articles presented a low level of evidence and showed diversity in question, methodology, and type of publication. For this reason, it was not possible to perform a quantifying review. Therefore, the articles are discussed in a descriptive manner with regard to the topic in question. Both orthodontic tooth movement and tooth eruption through grafted bone are not only possible but also might provide promising results. However, more research on this interdisciplinary treatment is necessary to avoid risks and achieve more safety in orthodontic treatment of these patients.

• The impact of bisphosphonates on the osteoblast proliferation and Collagen gene expression in vitro

  Authors: Felix Koch, Sareh Yekta, Christina Merkel, Thomas Ziebart, Ralf Smeets

  Head & Face Medicine. 01/2010;

  Abstract Background Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated withAbstract Background Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). The objective of this study was to evaluate the effect of bisphosphonates on osteoblast proliferation by cell count and gene expression analysis of cyclin D1 in vitro . Furthermore, the gene expression of the extracellular matrix protein collagen type I was evaluated. Nitrogen-containing and non-nitrogen-containing bisphosphonates have been compared on gene expression levels. Methods Human osteoblast obtained from hip bone were stimulated with zoledronate, ibandronate and clodronate at concentrations of 5 × 10^-5M over the experimental periods of 1, 2, 5, 10 and 14 days. At each point in time, the cells were dissolved, the mRNA extracted, and the gene expression level of cyclin D1 and collagen type I were quantified by Real-Time RT-PCR. The gene expression was compared to an unstimulated osteoblast cell culture for control. Results The proliferation appeared to have been influenced only to a small degree by bisphosphonates. Zolendronate led to a lower cyclin D1 gene expression after 10 days. The collagen gene expression was enhanced by nitrogen containing bisphosphonates, decreased however after day 10. The non-nitrogen-containing bisphosphonate clodronate, however, did not significantly influence cyclin D1 and collagen gene expression. Conclusions The above data suggest a limited influence of bisphosphonates on osteoblast proliferation, except for zoledronate. The extracellular matrix production seems to be initially advanced and inhibited after 10 days. Interestingly, clodronate has little influence on osteoblast proliferation and extracellular matrix production in terms of cyclin D1 and collagen gene expression.

• Analysis of trigeminal nerve disorders after oral and maxillofacial intervention

  Authors: Said Yekta Sareh, Felix Koch, Maurice Grosjean, Marcella Esteves-Oliveira, Jamal Stein, Alireza Ghassemi, Dieter Riediger, Friedrich Lampert, Ralf Smeets

  Head & Face Medicine. 01/2010;

  Abstract Background Quantitative sensory testing (QST) is applied to evaluate somatosensory nerve fiber function in the spinal system. This study uses QST in patients with sensory dysfunctions afterAbstract Background Quantitative sensory testing (QST) is applied to evaluate somatosensory nerve fiber function in the spinal system. This study uses QST in patients with sensory dysfunctions after oral and maxillofacial surgery. Methods Orofacial sensory functions were investigated by psychophysical means in 60 volunteers (30 patients with sensory disturbances and 30 control subjects) in innervation areas of the infraorbital, mental and lingual nerves. The patients were tested 1 week, 4 weeks, 7 weeks and 10 weeks following oral and maxillofacial surgery. Results QST monitored somatosensory deficits and recovery of trigeminal nerve functions in all patients. Significant differences (p < 0.05) between control group and patients were shown for cold, warm and mechanical detection thresholds and for cold, heat and mechanical pain thresholds. Additionally, QST monitored recovery of nerve functions in all patients. Conclusion QST can be applied for non-invasive assessment of sensory nerve function (Aβ-, Aδ- and C-fiber) in the orofacial region and is useful in the diagnosis of trigeminal nerve disorders in patients.

• The impact of bisphosphonates on the osteoblast proliferation and Collagen gene expression in vitro.

  Authors: Felix Peter Koch, Sareh Said Yekta, Christina Merkel, Thomas Ziebart, Ralf Smeets

  Head & face medicine. 01/2010; 6:12.

  Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jawBisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ).The objective of this study was to evaluate the effect of bisphosphonates on osteoblast proliferation by cell count and gene expression analysis of cyclin D1 in vitro. Furthermore, the gene expression of the extracellular matrix protein collagen type I was evaluated. Nitrogen-containing and non-nitrogen-containing bisphosphonates have been compared on gene expression levels. Human osteoblast obtained from hip bone were stimulated with zoledronate, ibandronate and clodronate at concentrations of 5 x 10-5M over the experimental periods of 1, 2, 5, 10 and 14 days. At each point in time, the cells were dissolved, the mRNA extracted, and the gene expression level of cyclin D1 and collagen type I were quantified by Real-Time RT-PCR. The gene expression was compared to an unstimulated osteoblast cell culture for control. The proliferation appeared to have been influenced only to a small degree by bisphosphonates. Zolendronate led to a lower cyclin D1 gene expression after 10 days. The collagen gene expression was enhanced by nitrogen containing bisphosphonates, decreased however after day 10. The non-nitrogen-containing bisphosphonate clodronate, however, did not significantly influence cyclin D1 and collagen gene expression. The above data suggest a limited influence of bisphosphonates on osteoblast proliferation, except for zoledronate. The extracellular matrix production seems to be initially advanced and inhibited after 10 days. Interestingly, clodronate has little influence on osteoblast proliferation and extracellular matrix production in terms of cyclin D1 and collagen gene expression.

• Gender specific quality of life in patients with oral squamous cell carcinomas.

  Authors: Oliver Maciejewski, Ralf Smeets, Frank Gerhards, Andreas Kolk, Frank Kloss, Jamal M Stein, Adrian Kasaj, Felix Koch, Maurice Grosjean, Dieter Riediger, Sareh Said Yekta

  Head & face medicine. 01/2010; 6:21.

  The goal of this study was to evaluate the somatic and psychological effects by means of QUALITY OF LIFE (QOL) of surgical treatment of patients with oral squamous cell carcinoma. The factors gender,The goal of this study was to evaluate the somatic and psychological effects by means of QUALITY OF LIFE (QOL) of surgical treatment of patients with oral squamous cell carcinoma. The factors gender, age, nicotine consumption, and tumour stage were taken into consideration. 54 patients after surgical resection of oral squamous cell carcinomas (OSCC) were analysed from 01.09.2005 to 31.05.2008. Inclusion criteria for the study were: age at least 18 years, no indication or treatment of synchronous and metachronous tumours. German translations of the EORTC H&N-35 and EORTC QLQ-C-30 questionnaires, as well as a general socioeconomic patient history were used as measuring instruments. The questionnaires were completed independently by the patients. The answers were translated into scale values for statistical evaluation using appropriate algorithms. Analysis of the EORTC-QLQ-C-30 questionnaires demonstrated a tendency of more negative assessment of emotional function among the female participants, and a more negative evaluation of social function among the male participants. Greater tumour sizes showed significantly lower bodily function (p = 0.018). While a smaller tumour size was significantly associated with lower cognitive functioning (p = 0.031). Other cofactors such as age, nicotine consumption, and tumour stage only showed a tendency to influence the quality of sleep and daily life. The data obtained within this investigation demonstrated that gender had the most significant power on the subjectively perceived postoperative quality of life. This factor is important e.g. in preoperative decision making regarding immediate microvascular reconstruction after e.g. mandibular resection and therefore QOL assessment should become integral component of the care of patients with OSCC.

• In vitro proliferation of human osteogenic cells in presence of different commercial bone substitute materials combined with enamel matrix derivatives.

  Authors: Christoph Reichert, Bilal Al-Nawas, Ralf Smeets, Adrian Kasaj, Werner Gotz, Marcus Klein

  Head & face medicine. 11/2009; 5(1):23.

  ABSTRACT: BACKGROUND: Cellular reactions to alloplastic bone substitute materials (BSM) are a subject of interest in basic research. In regenerative dentistry, these bone grafting materials areABSTRACT: BACKGROUND: Cellular reactions to alloplastic bone substitute materials (BSM) are a subject of interest in basic research. In regenerative dentistry, these bone grafting materials are routinely combined with enamel matrix derivatives (EMD) in order to additionally enhance tissue regeneration. Materials and Methods The aim of this study was to evaluate the proliferative activity of human osteogenic cells after incubation over a period of seven days with commercial BSM of various origin and chemical composition. Special focus was placed on the potential additional benefit of EMD on cellular proliferation. RESULTS: Except for PerioGlas(R), osteogenic cell proliferation was significantly promoted by the investigated BSM. The application of EMD alone also resulted in significantly increased cellular proliferation. However, a combination of BSM and EMD resulted in only a moderate additional enhancement of osteogenic cell proliferation. CONCLUSION: The application of most BSM, as well as the exclusive application of EMD demonstrated a positive impact on the proliferation of human osteogenic cells in vitro. In order to increase the benefit from substrate combination (BSM + EMD), further studies on the interactions between BSM and EMD are needed.

• Clinical evaluation of a biphasic calcium composite grafting material in the treatment of human periodontal intrabony defects: a 12-month randomized controlled clinical trial.

  Authors: Jamal M Stein, Stefan Fickl, Sareh Said Yekta, Ulrich Hoischen, Christina Ocklenburg, Ralf Smeets

  Journal of periodontology. 11/2009; 80(11):1774-82.

  BACKGROUND: The aim of this study was to compare the clinical outcome of a novel biphasic calcium composite (BCC) biomaterial versus autogenous bone spongiosa (ABS) or open flap debridement (OFD) forBACKGROUND: The aim of this study was to compare the clinical outcome of a novel biphasic calcium composite (BCC) biomaterial versus autogenous bone spongiosa (ABS) or open flap debridement (OFD) for the treatment of intrabony periodontal defects. METHODS: Forty-five subjects with at least one intrabony defect with a probing depth (PD) >or=7 mm and a vertical radiographic bone loss >or=3 mm were enrolled in the study. Subjects were randomly assigned to treatment with BCC (n = 15), ABS (n = 15), or OFD (n = 15). Clinical parameters were recorded at baseline and 12 months after surgery and included the plaque index, gingival index, PD, clinical attachment level (CAL), and gingival recession. RESULTS: In all treatment groups, significant PD reductions and CAL gains occurred during the study period (P <0.0001). At 12 months, patients treated with BCC exhibited a mean PD reduction of 3.6 +/- 0.7 mm and a mean CAL gain of 3.0 +/- 0.8 mm compared to baseline. Corresponding values for patients treated with ABS were 3.4 +/- 0.8 mm and 2.9 +/- 0.9 mm, whereas OFD sites produced values of 2.8 +/- 0.8 mm and 1.6 +/- 0.7 mm. Compared to OFD, the additional CAL gain was significantly greater in patients treated with BCC (P = 0.002) and ABS (P = 0.001). The additional PD reduction was significant for the BCC group (P = 0.011) and borderline significant for the ABS group (P = 0.059). There were no significant differences of PD and CAL changes between BCC and ABS groups. CONCLUSIONS: The clinical benefits of BCC were equivalent to ABS and superior to OFD alone. BCC may be an appropriate alternative to conventional graft materials.

• Clinical periodontal and microbiologic parameters in patients with acute myocardial infarction.

  Authors: Jamal M Stein, Bernhard Kuch, Georg Conrads, Stefan Fickl, Jaroslaw Chrobot, Susanne Schulz, Christina Ocklenburg, Ralf Smeets

  Journal of periodontology. 10/2009; 80(10):1581-9.

  Background: The aim of this study was to evaluate the impact of clinical periodontal parameters and the presence of periodontal pathogens in patients with acute myocardial infarction (AMI). Methods:Background: The aim of this study was to evaluate the impact of clinical periodontal parameters and the presence of periodontal pathogens in patients with acute myocardial infarction (AMI). Methods: A total of 104 subjects (54 patients with AMI and 50 healthy controls) were included. Subgingival plaque samples were analyzed for periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa; previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf; previously T. forsythensis), and Prevotella intermedia (Pi) using dot-blot hybridization. Results: Patients with AMI had a significantly higher frequency of probing depths (PDs) >/=4 mm than controls (39.2% versus 14.9%; P <0.0001). Among different cutoff levels, the frequency of >50% sites with PDs >/=4 mm showed the highest discrepancy between both groups (33% versus 0%; P <0.001). All periodontal pathogens were overrepresented in patients with AMI and positively correlated with increased periodontal PD and clinical attachment level (CAL). After adjustment for age, gender, smoking, body mass index, hypertension, plaque index, statin intake, and ratio of cholesterol to high-density lipoprotein, Pg remained a significant predictor for AMI (odds ratio [OR]: 13.6; 95% confidence interval [CI]: 3.1 to 59.8; P = 0.0005). Furthermore, the simultaneous presence of Aa + Pg (P = 0.0005) and Aa + Pg + Tf (P = 0.0018) were found with significantly higher frequency in patients with AMI than controls. Conclusions: The results of our study confirm an association between periodontitis and AMI in which periodontal destruction was correlated with the presence of periodontal pathogens. In particular, Pg might be considered a potential risk indicator for AMI.