Search

The alveolar ridge splitting technique enables reconstruction of atrophied alveolar ridges prior implantation. However, in cases of severe atrophy, there is an unpredictable risk of fracturing the buccal lamella during the expansion. Currently, there is no preoperative assessment to predict the maximum distraction of the lamella. The aim of this study was to develop a biomechanical model to mimic the alveolar ridge splitting and a finite element (FE) model to predict the experimental results. The biomechanical testing was conducted on porcine mandibles. To build the FE model high resolution peripheral quantitative computer tomography scans of one specimen was performed after the osteotomy outline, but before the lamella displacement. A servo-electric testing machine was used for the axial tension test to split the lamellae. Results showed, in line with clinical observations, that the lamellae broke primarily at the base of the splits with a median displacement of 1.27 mm. The FE model could predict fracture force and fracture displacement. Fracture force showed a nonlinear correlation with the height of the bone lamella. In conclusion, good correspondence between mechanical testing and virtual FE analysis showed a clinically relevant approach that may help to predict maximum lamella displacement to prevent fractures in the future.

The alveolar ridge splitting technique (ARST) offers an alternative to classic ridge augmentation techniques for successful insertion of dental implants. However, the buccal lamella is at risk of fracturing during ARST distraction. To better understand the fracture mechanisms and displacement limits of the split lamella, this study conducted biomechanical tests on human cadaveric maxilla specimens having extremely atrophied alveolar ridges treated with ARST. A total of 12 standardized alveolar splits were prepared on the maxillae of 3 elderly female donors using an oscillating piezoelectric saw. Mimicking the surgical distraction process of the lamella, each split was tested to failure using a dental osteotome attached to the crosshead of an electromechanical testing system. All specimens were scanned by means of high-resolution peripheral quantitative computed tomography prior to and post testing to evaluate split geometries and failure modes. Split stiffness, failure force, and displacement were 27.4 ± 18.7 N/mm, 12.0 ± 8.4 N, and 0.97 ± 0.31 mm, with no significant differences between anatomical sides and split locations ( p ≥ 0.17 ). Stiffness correlated significantly with failure force ( R 2 = 0.71 , p < 0.01 ). None of the alveolar split widths correlated significantly with the outcomes from biomechanical testing ( p ≥ 0.10 ). The results suggest that simple geometrical measures do not predict the allowed extent of lamella distraction prior to failure. More sophisticated methods are required for surgical planning to optimize the ARST outcomes. Still, the present study may advocate a clinical protocol for the maxilla where the implant site is prepared directly after osteotomy setting and immediately before full lamella dislocation, when the lamella is still stable, resistant to mechanical stress, and bone loss caused by the abrasion of the burr is minimized.

MatrixMANDIBLE Preformed Reconstruction Plates (MMPRPs) were developed to overcome laborious bending procedures of conventional reconstruction plates. The design comprises three sizes with a nonbendable centerpiece and two bendable sections (proximal and distal). According to the surgical protocol unnecessary parts are trimmed after the last used screw hole. In the present retrospective study postoperative radiographs from 130 patients (average age 63 years) that received treatment with MMPRPs were assessed. There was no statistical correlation between plate-size, location (left/right) or age. 82.98% of the small and 91.80% of the medium MMPRPs were trimmed by at least the terminal screw hole of the ramus part. In all patients receiving a large MMPRP, the terminal screw hole of the ramus was unused accordingly all inserted large MMPRPs were trimmed by at least the terminal screw hole. The majority of the bridged defects were located within the area of the body indicating a feasible plate design. With the emergence of solid free form fabrication of Ti-alloys and economic need to reduce the waste of resources this study may help to further improve the MMPRP design and prevent the loss of medical-grade titanium.

Tissue engineering applications, regenerative medicine, and cell therapy went from bench to bedside but still implicate the need for strategically planned investigations, controlled clinical application, as well as long-term follow-up to improve clinical evidence. Research in the field of tissue regeneration on the basis of mesenchymal stem cells is focused on many different factors to establish clinically relevant treatment modalities. To date, a direct translation of in vitro research into clinics provides promising results. Cell-based therapeutic concepts, successfully implemented in the field of maxillofacial surgery, comprise bone augmentation prior to implantation of dental implants as well as the combination of scaffolds with stem cells that will substitute bone grafts for large defects of the facial skeleton such as non-union.

Eine wichtige Voraussetzung zur Verbesserung von Operationsergebnissen ist die direkte intraoperative Kontrolle der chirurgischen Intervention durch geeignete Bildgebungsverfahren mit der Moglichkeit einer unmittelbaren Korrektur. Die digitale Volumentomographie (DVT), die Endoskopie sowie intraoperative Navigationssysteme verringern die Rate an notwendigen Zweiteingriffen. Der vorliegende Beitrag beschreibt aktuelle intraoperative Qualitatssicherungsmasnahmen in der Frakturversorgung und bei der Tumorbehandlung in der Kopf-Hals-Chirurgie.

In oral and maxillofacial surgery, autologous grafts from the iliac crest remain the 'gold standard' for alveolar ridge reconstruction, whereas intraoral bone grafts are considered in smaller defects. To date, a comparison of the osteogenic potential of osteoblasts with regard to their tissue origin is missing. Primary osteoblasts have proven useful for the investigation of the tissue-specific osteogenic properties. The present study compares primary human alveolar (aHOBs) and iliac osteoblasts (iHOBs) derived from three female patients undergoing routine intraoral bone grafting. Proliferation potential of the osteoblasts was evaluated using real-time impedance monitoring. Relative gene expression of bone specific biomarkers was analyzed and quantified using quantitative polymerase chain reactions (qPCR). Immunohistochemistry and phase contrast microscopy were performed, as well as alkaline phosphatase assay and alizarin red staining to visualize morphology and mineralization capacity. A twofold faster proliferation rate of aHOBs compared with iHOBs (130 h vs. 80 h) was observed. Alkaline phosphatase activity and alizarin red staining in both HOBs indicated similar mineralization capacity. Gene expression of seven genes (BMP1, CSF-1, TGFBR1, ICAM1, VCAM1, SPP1 and DLX5) was significantly higher in iHOB than in aHOB samples. These data suggest a higher osteogenic potential of osteoblasts derived from the iliac crest compared with primary osteoblasts from the alveolar bone and may lead to a better understanding of the molecular impact of bone cells from different bone entities on bone regeneration in alveolar ridge reconstructions.

Background A prerequisite of irradiation after advanced head and neck tumour resection is the accurate localization of the tumour resection margin. The purpose of the following study is to evaluate the use of surgical clips placed in the tumour resection margins for use as radiographic markers to facilitate focussed adjuvant radiation therapy. Materials To evaluate whether the clips remain predictive for the resection margin, we analysed the deviation of each clip in two postoperative CT scans on different days. Bone registration points were used to fuse the two CT scans in the region of the primary tumour and the distances between corresponding clips were measured. Results The tumour resection margins were labelled with an average of 18 titanium clips. In total 282 clips were evaluated. Metric analysis of clip deviation between the two postoperative CT scans found a mean distance of 4.5 mm±2.5 mm with a range of 0.5–11.8 mm. No significant statistical relationship of the clip differences as a function of time, the method of reconstruction or administered radiotherapy could be demonstrated. Conclusion Placement of surgical clips in the cavity walls after complete tumour resection provides an easy and inexpensive approach for defining resection margins and allows for increased accuracy of adjuvant treatment. Clinical trial number DRKS00007534.

Long-term results of reconstructions and prosthetic rehabilitation of patients presenting severely atrophied edentulous ridges remains a challenge for clinicians. Among the various available augmentation materials there is evidence that avascular fibula bone grafts possess a reliable resistance against resorption and may thus provide a valuable source to reduce the loss of vertical bone height after reconstruction of the severely atrophied mandible and maxilla. The purpose of the present study was to assess long-term crestal bone level stability in avascular fibula bone grafts. 8 edentulous female patients (average age 70.6 years) with Class-VI-atrophy and less than 5 mm residual bone volume received onlay-grafting with avascular fibula bone grafts and were monitored with a mean observation time of 133.7 months (121-186). A total of 39 implants were placed in the maxilla and mandible. Three patients received immediate and five patients delayed implant placement 3 months after grafting. All patients were provided with bar-retained dentures. Postoperative evaluation included clinical implant success (Buser) and radiographic examinations (orthopantomogram) to quantify crestal bone resorption. Grafting was successfully performed in all patients with no regrafting necessary. All implants but one, lost 2 years after abutment connection, remained successfully integrated and fulfilled the Buser criteria, rendering to a success rate of 97%. Mean bone resorption after 10 years was mesial 1.4 mm and distal 1.4 mm at each implant-site. Maximum bone resorption occurred between postoperative and first year, thereafter no significant resorption was measured in re-examinations up to 15 years. Avascular fibula grafts are a reliable bone graft for augmentation procedures in atrophied edentulous ridges. Dental implants that integrated in the autogenous fibular bone grafts showed a stable crestal peri-implant bone level up to 15 years after implant placement.

BMP-2 and TGF-β1 released from injectable thermoresponsive hydrogels are studied in the presence and absence of branched macromolecules bearing BMP-2 or TGF-β1 affinity binding peptides. The synthesized branched macromolecules and the gelling compositions before and after loading with either BMP-2 or TGF-β1 are characterized physico-chemically and show a significantly lower amount of proteins released in the presence of the affinity binding peptide macromolecules. This study illustrates the potential of affinity binding peptide functionalized dendrimers to modulate the local delivery and availability of growth factors important for musculoskeletal regeneration therapies.

Accurate localization of tumor resection borders is crucial for adjuvant radiotherapy. An improvement to adjuvant radiotherapy with the reduction of radiation doses to free flap reconstruction by virtual navigation procedures and titanium clips was evaluated. Thirty-three patients with oral cancer were prospectively included in the study. Following complete local excision of the primary tumor, resection borders were marked virtually using a navigation pointer and with titanium ligature clips. Postoperative delineation of tumor resection borders was examined. In five patients with microvascular free flap reconstruction a reduction of the radiation dose to the free flap reconstruction was achieved. The tumor resection borders in 30 patients were marked with titanium ligature clips. Surgical clip insertion was successful in 91%. We demonstrate a significant relationship between the reconstruction volume and the part of the target volume which will receive a reduced radiation dose. A cumulative dose of 60 Gy was administered to the target volume and a significant reduction of the administered radiation dose to the center of the flap could be demonstrated. We demonstrate an accurate delineation of the tumor resection margins. These improvements in tumor resection margin delineation allow for increased accuracy in adjuvant treatment and a reduction of radiation dose to the vascular free flap reconstruction.

In bone tissue engineering (TE) endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs) are a rich source of mesenchymal stem cells (MSCs) able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs) are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+and CD133+) were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+) or medium containing platelet lysate (PL). MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.

The purpose of this study was to evaluate the long-term survival rate and potential influencing factors of dental implants and implant-retained prostheses in oral cancer patients who had undergone surgical tumor resection. In the present study, 157 patients (95 females and 62 males with a mean age of 53.7 years) with 830 implants were included. All patients were diagnosed with a malignant tumor in the oral cavity and had undergone ablative surgery. In 55 patients (292 implants), the surgical procedure was followed by an additional radiochemotherapy (RCT) before implant placement. Nicotine users who received RCT were excluded from this study. Patients were clinically examined every 6 or 12 months according to a standard procedure. Of the 830 examined implants, 450 were placed in the maxilla and 380 in the mandible. A total of 65 implants were lost, 36 in the maxilla and 29 in the mandible; of these, 42 implants (65 %) were documented as lost due to the patient’s death. The mean observation period was 121 months. The cumulative survival rate was 94.9 % at 3 years and 92.5 % at 7 years. With an observation period up to 20 years, the cumulative survival rate remained constant after 11 years with 90.8 %. Age, gender, and localization (maxilla/mandible) of implants did not show any influence on the survival of the implants. However, radiochemotherapy was determined as a significant factor influencing the survival rate. The results of this study demonstrate that the survival rate of implants was significantly lower in oral cancer patients who had been treated by ablative surgery and additional radiochemotherapy than in patients without RCT. Since there is no significant difference in the mortality rate of patients with additional RCT compared to patients who underwent sole ablative surgery, the higher loss ratio is due to a late failure of osseointegration. Dental implants in oral cancer patients who had been treated by ablative surgery show a high and steady cumulative survival rate after 11 years. Implant survival of patients with additional RCT is significantly lower. Non-smoking-irradiated patients seem to have a better implant survival.

The controlled presentation of biofunctionality is of key importance for hydrogel applications in cell-based regenerative medicine. Here, a versatile approach was demonstrated to present clustered binding epitopes in an injectable, thermoresponsive hydrogel. Well-defined multivalent dendrimers bearing four integrin binding sequences and an azido moiety were covalently grafted to propargylamine-derived hyaluronic acid (Hyal-pa) using copper-catalyzed alkyne-azide cycloaddition (CuAAC), and then combined with pN-modified hyaluronan (Hyal-pN). The dendrimers were prepared by synthesizing a bifunctional diethylenetriamine pentaacetic acid core with azido and NHBoc oligo(ethylene glycol) aminoethyl branches, then further conjugated with solid-phase synthesized RGDS and DGRS peptides. Azido terminated pN was synthesized by reversible addition-fragmentation chain transfer polymerization and reacted to Hyal-pa via CuAAC. Nuclear magnetic resonance (NMR), high performance liquid chromatography, size exclusion chromatography and mass spectroscopy proved that the dendrimers had well-defined size and were disubstituted. NMR and atomic absorption analysis confirmed the hyaluronan was affixed with dendrimers or pN. Rheological measurements demonstrated that dendrimers do not influence the elastic or viscous moduli of thermoresponsive hyaluronan compositions at a relevant biological concentration. Finally, human mesenchymal stromal cells were encapsulated in the biomaterial and cultured for 21days, demonstrating the faculty of this dendrimer-modified hydrogel as a molecular toolbox for tailoring the biofunctionality of thermoresponsive hyaluronan carriers for biomedical applications.

Objectives X-ray-based planning and post-implantation assessment of titanium implants is the commonly accepted standard to date. However, new implant materials such as zirconia (ZrO2) have become available, and magnetic resonance imaging may be a valuable alternative with these implants. The present in vitro study investigated artifacts produced by titanium and zirconia implants in magnetic resonance imaging (MRI) and assessed the accuracy of pre-implant planning and post-implantation assessment comparing MRI to standard X-ray-based imaging modalities: Orthopantomogram (OPT), cone beam (CBCT), and computed tomography (CT). Materials and methods Twelve porcine mandibles were prepared and scanned (MRI, OPT, CBCT, μCT), and bone height above the nerve canal was measured. Specimens were implanted with either two titanium or zirconia implants and rescanned to investigate the influence of implant materials on post-implantation assessment. MRI and μCT artifacts were quantified with implants embedded in gelatin phantoms and porcine specimens. Results Compared with CBCT set as standard, μCT, OPT, and MRI showed similar accuracy in pre-op bone height measurements. Post-implantation, while titanium implants induced a strong B0-field distortion resulting in extensive signal voids, zirconia implants were clearly depictable with only minor distortions. Conclusions Excellent contrast, limited artifacts, radiation-free and accurate implant assessment may indicate that MRI is a valuable imaging alternative for zirconia-based implant dentistry.

PURPOSE Classic tissue engineering consists of three components: scaffold, cells, and growth or differentiation factors. Currently, expensive bone morphogenetic proteins are the most common substance used for hard tissue regeneration. An alternative could be gamma-aminobutyric acid/lactam (GABA-lactam) analogs. MATERIALS AND METHODS The effects of gabapentin-lactam, cis- and trans-8-tertbutyl-GABA-pentinlactam (trans-TB-GBP-L), and phenyl-GABA-lactam were tested in this study on ovine mesenchymal stem cell (MSC) proliferation. MSCs were selected from bone marrow aspirate concentrate by plastic adherence and amplified. Aliquots of the cells were incubated in medium, with four different concentrations of the GABA-lactam analogs dissolved in dimethyl sulfoxide. Cells in medium with and without dimethyl sulfoxide served as controls. Cell proliferation was tested with a nonradioactive assay. Before and after GABA-lactam analog influence, the MSC character was evaluated by the ability of the cells to differentiate into osteoblasts, chondrocytes, and adipocytes. RESULTS Proliferation was significantly increased under the influence of the analogs, depending on their concentration. MSCs cultured in 1 nmol/L trans-TB-GBP-L showed the highest proliferation rate. The MSC character was not altered. CONCLUSIONS GABA-lactam analogs could be suited to stimulate MSC proliferation for tissue engineering applications. Further in vivo studies are necessary to evaluate the possible clinical potential of GABA-lactam analogs for hard tissue regeneration.

Introduction.Human mesenchymal stromal cells (hMSCs) exhibit the potential to accelerate bone healing by enhanced osteogenic differentiation. Interleukin-1βis highly expressed during fracture healing and has been demonstrated to exert a significant impact on the differentiation behaviour of hMSCs. Here, we investigate the effect of 2-hour IL-1βstimulation on the differentiation and paracrine activity of hMSCs in coculture with osteosarcoma cellsin vitro.Methods.hMSCs from 3 donors were incubated for 2 hours with 10 ng/mL IL-1βand subsequently cocultured with MG63-GFP cells either in control or in differentiation medium in a transwell system for 28 days. Genetic and functional effects were investigated.Results.hMSCs cultured in control medium exhibited a regulatory effect on cocultured MG63-GFP cells, resulting in upregulation of osteogenic gene expression in combination with increased ALP activity. However, while stimulated hMSCs cultured under differentiation conditions exhibit signs of osteogenic differentiation, osteogenic differentiation also caused an impaired regulatory effect on the cocultured MG63-GFP cells.Conclusion.Short stimulation of hMSCs has the potential to modify their long-term behaviour. In addition, undifferentiated hMSCs are able to regulate osteoblast differentiation; however, this regulatory function is lost upon osteogenic differentiationin vitro. This offers a novel approach for clinical cell therapy protocols.

BMP-2 and TGF-β1 released from injectable thermoresponsive hydrogels are studied in the presence and absence of branched macromolecules bearing BMP-2 or TGF-β1 affinity binding peptides. The synthesized branched macromolecules and the gelling compositions before and after loading with either BMP-2 or TGF-β1 are characterized physico-chemically and show a significantly lower amount of proteins released in the presence of the affinity binding peptide macromolecules. This study illustrates the potential of affinity binding peptide functionalized dendrimers to modulate the local delivery and availability of growth factors important for musculoskeletal regeneration therapies.

Introduction The aim of this work was to analyse the suitability of mesenchymal stem cell isolation by FICOLL density centrifugation and the closed bone marrow aspirate concentrate (BMAC) system for sinus augmentation with bovine bone mineral (BBM) in the sheep model. Methods 16 sheep underwent sinus augmentation with BBM and MSCs; they were divided between two groups with survival points of 8 and 16 weeks. For the FICOLL control arm three, and for the BMAC test arm, five augmentations were performed for each time point. The derived cell numbers were counted; a colony forming unit (CFU) assay was performed; the pluripotency of the MSCs was proved; histological and histomorphometrical analysis were performed. Results The approach of using BBM and MSCs in combination with fibrin adhesive was sufficient for new bone formation as the FICOLL experiment indicated. However, due to significantly lower cell numbers isolated using the BMAC in sheep, less new bone was formed in the test arm. Conclusions The BMAC system is well suited for human MSC isolation but it needs to be optimized to fit sheep cell characteristics if it is to be used in this animal model.

Communication between the surgeon and the radiation oncologist is improved with the use of virtual models of the final tumour resection, combining three-dimensional imaging and conventional clip marking with computer-aided navigation. This investigation was designed to determine the deviation of virtual marking procedures compared to conventional marking by titanium ligature clips in oral cancer with different localizations. Seventeen patients with surgically placed clips and virtual landmarks on the resection margin after complete tumour ablation were evaluated. To determine whether the virtual landmarks remain predictive of the resection margin, the deviation of the virtual points from their corresponding clips was analyzed by measuring the distance between their centres of gravity. In total, 189 clips were evaluated. Metric analyses of the deviation between the virtual points and clips showed a deviation of 2.3 ± 0.6mm for tumours with a maxilla localization, 7.2 ± 2.5mm for tumours with a mandible localization, and 12.6 ± 3.8mm for tumours with a tongue localization. A significant statistical relationship was demonstrated in the virtual point-clip deviation as a function of tumour localization. Virtual marking of maxillary tumour resection margins allows accurate definition of the former tumour bed and could lead to novel adjuvant treatment strategies.

The aim of this case series was to clinically demonstrate successful prevention of bone resorption of the buccal wall after alveolar bone splitting by additional stabilization of the lateral bone plate using a biphasic ceramic bone substitute. In three patients alveolar bone splitting was performed with a piezoelectric device. Clinical as well as radiological results after two and five years revealed stable hard and soft tissue conditions with no soft tissue recessions and peri-implant bone loss in three patients. The advantage of this one-stage procedure was the ability to insert dental implants into a very compromised bony site in a simultaneous procedure. Yet the bone splitting stabilisation technique appeared to be a more user-sensitive method.

Purpose Successful repair and regeneration in bone tissue engineering vastly depends on proper interaction between the tissue-engineered construct and the recipient's immune system. In clinical application, adverse responses to bioartificial implants may result in chronic inflammation and loss of the implant. It is known that prolonged inflammation linked to NF-κB inflammatory pathways inhibits bone-forming activity of osteoblast cells. Contributing to orchestrate inflammatory processes, the ligand-activated transcription factor peroxisome proliferator-activated receptor alpha (PPARα) holds inhibitory effects on NF-κB and CEBβ activity. Sp1, a widely expressed transcription factor, has been linked to PPAR pathways, cellular homeostasis, and responsiveness to environmental perturbation. Formerly not being characterized, the role of PPARα in inflammatory-mediated bone loss requires further investigation. The aim of the present study was to identify regulatory transcription factor binding sites (TFBS) on the PPAR alpha promoter and to assess the role of Sp1 and associated proteins in its regulation. Materials and methods In a first set of experiments, polymerase chain reaction assessed the presence of PPARα gene expression in isolated murine bone tissue. Deletion mutagenesis was performed on the human PPARα (hPPARα) promoter gene, and the deletion constructs were transiently transfected to murine osteoblasts to identify important TFBS. PPARα promoter-driven reporter gene expression was monitored in response to overexpression and repression of Sp1 to analyze functional transcription factor recruitment to the PPARα promoter. Results This study could demonstrate that the full-length hPPARα promoter contains inhibiting promoter regions and that hPPARα basal expression can be significantly increased by deletion mutagensis. Sp1 TFBS proved functional in the regulation of PPARα promoter activity, and the first five Sp1 motifs on the PPARα promoter were sufficient to significantly increase PPARα expression. Additional transient co-transfection experiments could not detect any direct effect of NF-κB/IκB downstream pathway on the regulation of PPARα promoter activity. Taken together, we could demonstrate that Sp1 plays a key role in transcriptional regulation of PPARα promoter activity and gene expression. Conclusion This study provides further insight on Sp1-dependent PPARα regulatory mechanisms and suggests that Sp1-regulated PPARα expression plays a key role in inflammatory mediated bone loss.

Purpose: Modern bone tissue engineering associated with mesenchymal stem cells (MSCs) provides promising treatment alternatives for the loss of bone, one of the foremost challenges in oral and craniofacial surgery today. The effect of gabapentin-lactam (GBP-L) and its analogs on osteogenic differentiated MSCs has not yet been deciphered. Consequently, this study investigates the effect of novel trans-8- tertbutylgabapentin-lactam (trans-8-TB-GBP-L) hydroxamic acid derivatives on metabolism, proliferation, and physiologic mineralization characteristics of ovine osteoblast cells. Materials and Methods: Osteoblasts were extracted and prepared from sheep femoral heads and cultured in medium enriched with hydroxamic acid derivatives of trans-8-TB-GBP-L. The cell proliferation rate, cell metabolism, cell viability, and basic osteoblastic function were assessed. Results: After 3 and 5 days of incubation, no significant increase in DNA content was detected in any of 12 test groups versus the control group. However, after 8 days of incubation, a significant increase of DNA contents in the test groups containing nanomolar concentrations of trans-8-TB-GBP-L hydroxamic acid derivatives was found. No significant aberration in metabolic activity was detected when any of the test substances were applied. ALP displayed similar activity rates among the test groups and the control at all time points. Calcification of osteoblastic cells occurred solely when nanomolar concentrations were used. Conclusion: Trans- 8-TB-GBP-L hydroxamic acid derivatives do not interfere with physiologic function and phenotype of ovine osteoblasts. However, when applied at nanomolar concentrations, the assessed GBP-L derivatives significantly increased the cell proliferation rate after 8 days of incubation, indicating a doseresponse curve with the maximum peak at nanomolar concentration and a retarded drug response between 5 and 8 days.

Tissue engineering techniques for the regeneration of large bone defects require sufficient vascularisation of the applied constructs to ensure a sufficient supply of oxygen and nutrients. In our previous work, prevascularised 3D scaffolds have been successfully established by coculture of bone marrow derived stem cells (MSCs) and endothelial progenitor cells (EPCs). We identified stabilising pericytes (PCs) as part of newly formed capillary-like structures. In the present study, we report preliminary data on the interactions between MSCs and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs were seeded in transwell cultures, direct cocultures, and single cultures. Cells were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate medium. Gene expression of PC markers, CD146, NG2, αSMA, and PDGFR-β, was analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2, and αSMA in MSCs in direct coculture with EPCs advocates the MSCs' differentiation towards a pericyte-like phenotype in vitro. These results suggest that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is an important factor for this differentiation process. These findings emphasise the concept of coculture strategies to promote angiogenesis for cell-based tissue engineered bone grafts.

Purpose Novel gabapentin-lactam (GBP-L) has shown its potency in enhancing new bone formation (NBF) in vitro. The objective of the present preclinical trial was to investigate the in vivo performance of GBP-L. Materials and Methods Bilateral sinus floor augmentations in 10 adult sheep were conducted. Bovine bone mineral (BBM) and mesenchymal stem cells (MSCs) combined with novel GBP-L were placed into the test sinus of each sheep. The BBM and MSCs alone served as the control on the contralateral side. Simultaneously, 3 dental implants were inserted in each maxillary sinus. The animals were sacrificed after 8 and 16 weeks, and the amount of NBF was analyzed using histomorphometry. The osteogenic potency of the MSCs was demonstrated using the colony-forming unit and differentiation assay. Statistical evaluation was performed using the Wilcoxon signed rank test and 3-factorial nonparametric analysis of variance. Results The histologic examination showed NBF in tight contact with the original bone in the control and test groups. The NBF was not significantly different between the test and control sites (P > .05). However, a highly significant difference in NBF between the apical and coronal sites in the specimens from the control and test groups was detected (P Conclusions Bone formation is initiated from the residual alveolar crest and along the implant. The elected mode of GBP-L application did not induce faster NBF. Alternate forms of application (eg, slow release or systemic administration) might clarify the controversial in vitro findings.

Background A prevalent modality to increase the amount of available bone prior to implantation is grafting of the maxillary sinus. Multiple factors such as the surgical technique, moment of implant placement as well as grafting materials and membranes are known to affect implant survival. However, the role of different factor combinations and associated reciprocal effects remain unclear. Conventional statistical methods do not consider inconsistency of study designs and do not take covariables into account. Hence, a systematic research and meta-analysis was conducted to investigate the influence of various treatment modalities on implant survival in the grafted maxillary sinus. Materials and Methods A meta-analysis was conducted according to the PRISMA guidelines. Articles published from 1980 through January 2013 were electronically and manually searched in MEDLINE (Ovid), the Cochrane Register of Controlled Trials, the Database of Abstracts of Effects, and the Cochrane Database of Systematic Reviews. Clinical reports on single intervention sinus augmentation with root-form implants, a minimum of 10 patients and 6 months of loading were eligible for inclusion if implant survival was stated or calculable. Results were calculated by non-parametric univariate Kaplan-Meier analysis and Bayesian multivariate interval-censored Cox regression. Results A total of 122 publications on 16268 endosseous implants placed in grafted maxillary sinus were included. The treatment parameters surgical approach, grafting material and implant type showed no selective preference. However, application of membranes showed a significantly reduced hazard-ratio, independent of other co-factors. Conclusions The use of membranes is the most significant factor to achieve long-term implant survival in sinus augmentation procedures. More data exceeding 3 years follow-up are needed to address prospective confounding and improve clinical evidence.

Over the last decade tissue engineering has emerged as a key factor in bone regeneration within the field of cranio-maxillofacial surgery. Despite this in vivo analysis of tissue-engineered-constructs to monitor bone rehabilitation are difficult to conduct. Novel high-resolving flat-panel based volume CTs (fp-VCT) are increasingly used for imaging bone structures. This study compares the potential value of novel fp-VCT with conventional multidetector CT (MDCT) based on a sheep sinus floor elevation model. Calcium-hydroxyapatite reinforced collagen scaffolds were populated with autologous osteoblasts and implanted into sheep maxillary sinus. After 8, 16 and 24 weeks MDCT and fp-VCT scans were performed to investigate the volume of the augmented area; densities of cancellous and compact bone were assessed as comparative values. fp-VCT imaging resulted in higher spatial resolution, which was advantageous when separating closely related anatomical structures (i.e. trabecular and compact bone, biomaterials). Fp-VCT facilitated imaging of alterations occurring in test specimens over time. fp-VCTs therefore displayed high volume coverage, dynamic imaging potential and superior performance when investigating superfine bone structures and bone remodelling of biomaterials. Thus, fp-VCTs may be a suitable instrument for intraoperative imaging and future in vivo tissue-engineering studies.

Blood supply is a critical issue in most tissue engineering approaches for large defect healing. As vessel ingrowth from surrounding tissues is proven to be insufficient, current strategies are focusing on the neo-vascularisation process. In the present study, we developed an in vitro pre-vascularised construct using 3D polyurethane (PU) scaffolds, based on the association of human Endothelial Progenitor Cells (EPC, CD34+ and CD133+) with human Mesenchymal Stem Cells (MSC). We showed the formation of luminal tubular structures in the co-seeded scaffolds as early as day 7 in culture. These tubular structures were proven positive for endothelial markers von Willebrand Factor and PECAM-1. Of special significance in our constructs is the presence of CD146-positive cells, as a part of the neovasculature scaffolding. These cells, coming from the mesenchymal stem cells population (MSC or EPC-depleted MSC), also expressed other markers of pericyte cells (NG2 and αSMA) that are known to play a pivotal function in the stabilisation of newly formed pre-vascular networks. In parallel, in co-cultures, osteogenic differentiation of MSCs occurred earlier when compared to MSCs monocultures, suggesting the close cooperation between the two cell populations. The presence of angiogenic factors (from autologous platelet lysates) in association with osteogenic factors seems to be crucial for both cell populations' cooperation. These results are promising for future clinical applications, as all components (cells, growth factors) can be prepared in an autologous way.