A prospective histomorphometric and cephalometric comparison of bovine bone substitute and autogenous bone grafting in Le Fort I osteotomies.

PURPOSE: The aim of the present study was the histomorphometric and cephalometric comparison of autogenous bone grafting of the anterior iliac crest and the application of bovine bone substitute concerning new bone formation and postoperative stability in patients undergoing orthognathic Le Fort I osteotomy. PATIENTS AND METHODS: Twenty-five patients requiring orthognathic surgery with Le Fort I osteotomy were included in this study. Patients were randomly divided into three groups receiving either autogenous iliac crest BONE grafting (BONE; n = 8) or xenogenic bovine bone grafting (Bio-Oss®) in INTER (n = 12) or in ONLAY (n = 5) position. Histomorphometric analysis was performed using trephine bone biopsies from the autogenous, respectively xenogenic bone grafting region. Postoperative stability was evaluated using teleradiographies of three different timepoints. RESULTS: All groups showed comparable mineralized fractions in bone biopsies of 50.2% (±13.2%) INTER, 46.48% (±12.3%) ONLAY and 57.1% (±20.6%) BONE as well as comparable percentage of connective tissue. Patients in the INTER-group revealed the lowest relapse rate of 20.5% (INTER) compared to 30.3% (ONLAY) and 33.0% (BONE). All groups underwent comparable maxillary advancement and healing time. CONCLUSIONS: Present results indicate that block shaped bovine bone substitute is a promising alternative to autogenous bone grafting to bridge the Le Fort I osteotomy gap in orthognathic surgery.

Sinus Floor Augmentation Comparing an In Situ Hardening Biphasic Calcium Phosphate (Hydroxyapatite/ß-Tricalcium Phosphate) Bone Graft Substitute with a Particulate Biphasic Calcium Phosphate (Hydroxyapatite/ß-Tricalcium Phosphate) Bone Graft Substitute: An Experimental Study in Sheep.

OBJECTIVE: The aim of the present split-mouth study in sheep was to assess the influence of in situ hardening properties of a biphasic calcium phosphate (BCP) bone graft substitute (BGS) (ratio hydroxyapatite/ß-tricalcium phosphate = 60/40) compared with a particulate BGS with the same biphasic core-granule composition without in situ hardening properties on sinus floor augmentation. MATERIALS AND METHODS: Therefore, bilateral sinus floor augmentation was performed in eight sheep. Poly(lactide-co-glycolide) (PLGA)-coated, in situ hardening biphasic BGS (PLGA-NMP [N-Methyl-2-pyrrolidone]-BCP) was placed at the test site, and a particulate biphasic BGS without PLGA coating (BCP) was used for the contralateral site as a control. Animals were sacrificed after 21 weeks. Sinus augmentation sites were analyzed histologically. The volume was analyzed by computed tomography. Histomorphometric parameters were assessed for the 12 and 21 weeks' time points. Slopes of new bone formation over time were compared with a linear growth regression model. RESULTS: Bone formation after 12 and 21 weeks of healing was 8.94% (±3.74) and 19.82% (±6.29) for PLGA-NMP-BCP and 7.00% (±2.58) and 14.38% (±4.51) for BCP, respectively. The bone growth rate for PLGA-NMP-BCP was higher than the growth rate for BCP (probability 97.5%). The total fraction of calcified hard tissue (% bone fraction + % biomaterial) was around 46% for both tested biomaterials, 21 weeks after sinus floor augmentation. CONCLUSION: The in situ hardening BGS (PLGA-NMP-BCP) performed better than the particulate material (BCP) in terms of bone formation rate. The in situ hardening properties of the PLGA-NMP-BCP material mediated by the PLGA coating and NMP solution as plasticizer had no negative influence on the bone formation.

Injectable Hyaluronan Hydrogels with Peptide-Binding Dendrimers Modulate the Controlled Release of BMP-2 and TGF-ß1.

BMP-2 and TGF-ß1 released from injectable thermoresponsive hydrogels are studied in the presence and absence of branched macromolecules bearing BMP-2 or TGF-ß1 affinity binding peptides. The synthesized branched macromolecules and the gelling compositions before and after loading with either BMP-2 or TGF-ß1 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.

Magnetic resonance imaging in zirconia-based dental implantology.

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.

Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels.

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.

Follow-up of implant survival comparing ficoll and bone marrow aspirate concentrate methods for hard tissue regeneration with mesenchymal stem cells in humans.

OBJECTIVE: Clinical follow-up of implant survival in 11 patients comparing two different methods for mesenchymal stem cell (MSC) isolation (Ficoll and bone marrow aspirate concentrate [BMAC]) applied in maxillary sinus augmentation. METHODS: Mononuclear cells, including MSCs, were concentrated with either Ficoll (control group, n=6 sinus) or BMAC (test group, n=12 sinus) and transplanted in combination with bovine bone mineral. A total of 50 implants were placed in a second surgical intervention (17 Ficoll/33 BMAC) and loaded after 4 months. Overall implant survival was assessed with a Kaplan-Meier model using package survival under R. RESULTS: Implant survival of the Ficoll group was 100% compared with the BMAC group, which had 93.4% survival (95% confidence interval, 0.849-1). The difference between the groups was not significant (p=0.381). CONCLUSION: The BMAC system is an effective and suitable "chair-side" method for clinical application in hard tissue regeneration.

Can mesenchymal stem cells and novel gabapentin-lactam enhance maxillary bone formation?

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 < .05). GBP-L did not alter the multipotency of the MSCs or impair NBF. 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.

Sp1-dependent regulation of PPARα in bone metabolism.

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 CEBß 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.

The effect of gabapentin-lactam hydroxamic acid derivatives on ovine osteoblast proliferation and phenotype: perspectives for tissue engineering application.

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 dose-response curve with the maximum peak at nanomolar concentration and a retarded drug response between 5 and 8 days.

Impact of autogenous concentrated bone marrow aspirate on bone regeneration after sinus floor augmentation with a bovine bone substitute--a split-mouth pilot study.

PURPOSE: Mesenchymal stem cells (MSC) with biomaterials have osteoinductive potential. The aim of this study was to evaluate early bone formation in xenogenic sinus grafts in a direct comparison with and without MSCs after 3 and 6 months. Literature on bone formation in pure xenogenic graft materials after 3 months in a human model is still lacking. MATERIALS AND METHODS: In a split-mouth design, seven patients with a bilateral highly atrophic posterior maxilla were included. The test side was grafted with MSCs from concentrated bone marrow aspirate admixed to the bone graft material. On the control side, pure bovine bone material was applied. Biopsies were taken navigated after 3 and 6 months. RESULTS: After 3 months, new bone formation in the control group was 11.8% (SD 6.2%) and in the test group 7.4% (SD 4.1%). After 6 months, the control group showed 13.9% (SD 8.5%) of new bone and the test group 13.5% NB (SD 5.4%). The fraction of bovine bone material after 3 months was 42.6% (SD 3.5%) in the test group and 34.9% (SD 11.8%) in the control group. After 6 months, the biomaterial content was comparable at both sides (test 36.2%, SD 7.8%; control 39.5%, SD 9.3%). CONCLUSIONS: There was no significant difference in new bone formation between the test and control group with n = 7. The results may be dominated by the high mineral content of the biomaterial but could nevertheless be valuable for meta-analysis in the future.

Evaluation of a new experimental model to study bone healing after ridge expansion with simultaneous implant placement--a pilot study in minipigs.

OBJECTIVE: To evaluate the suitability of a minipig model for the study of bone healing and osseointegration of dental implants following bone splitting and expansion of narrow ridges. MATERIAL AND METHODS: In four minipigs, the mandibular premolars and first molars were extracted together with removal of the buccal bone plate. Three months later, ridge splitting and expansion was performed with simultaneous placement of three titanium implants per quadrant. On one side of the mandible, the expanded bone gap between the implants was filled with an alloplastic biphasic calcium phosphate (BCP) material, while the gap on the other side was left unfilled. A barrier membrane was placed in half of the quadrants. After a healing period of 6 weeks, the animals were sacrificed for histological evaluation. RESULTS: In all groups, no bone fractures occurred, no implants were lost, all 24 implants were osseointegrated, and the gap created by bone splitting was filled with new bone, irrespective of whether BCP or a barrier membrane was used. Slight exposure of five implants was observed, but did not lead to implant loss. The level of the most coronal bone-to-implant contact varied without being dependent on the use of BCP or a barrier membrane. In all groups, the BCP particles were not present deep in the bone-filled gap. However, BCP particles were seen at the crestal bone margin, where they were partly integrated in the new bone. CONCLUSIONS: This new minipig model holds great promise for studying experimental ridge splitting/expansion. However, efforts must be undertaken to reduce implant exposure and buccal bone resorption.

Long-term survival of dental implants placed in the grafted maxillary sinus: systematic review and meta-analysis of treatment modalities.

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.

Effect of gabapentin-lactam and gamma-aminobutyric acid/lactam analogs on proliferation and phenotype of ovine mesenchymal stem cells.

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.

Bone marrow aspirate concentrate used with bovine bone mineral to reconstruct vertical and horizontal mandibular defects: report of two techniques.

PURPOSE: Following initial positive reports of the use of bone marrow aspirate concentrate (BMAC) in combination with bovine bone mineral (BBM) in augmentation procedures, the technique was evaluated in patients with mandibular deficiency. MATERIALS AND METHODS: Two adult patients required surgical correction of a deficient alveolar ridge (one patient showed horizontal deficiency only, and the other patient presented with horizontal and vertical deficiency) prior to dental implant placement. In both patients, the reconstruction was performed with BBM in combination with mononuclear cells concentrated by the BMAC method using different techniques. RESULTS: The patients recovered well from all surgical procedures. Histologically, there was uniform bone formation, which allowed placement of dental implants. CONCLUSION: The results suggest that the use of BMAC in combination with BBM, without autogenous bone, has the potential to restore horizontal and vertical mandibular alveolar defects, providing a functional bone structure and allowing dental implant placement for subsequent prosthetic rehabilitation.

Evaluation of bone substitute materials: comparison of flat-panel based volume CT to conventional multidetector CT.

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.

Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: technical report and follow up of 21 patients.

INTRODUCTION: Bisphosphonates are used to reduce skeletal related events in patients with bone consuming diseases such as osteoporosis and bone metastases. However recently there has been an increased awareness of bisphosphonate-associated necrosis of the jaws (BP-ONJ). Many authors propose conservative management in these cases but invariably the problem is not treated successfully allowing the bone defect to worsen. Recently there has been a move to treat this problem surgically. The aim of this retrospective study was to provide a surgical solution for patients suffering from BP-ONJ. MATERIALS AND METHODS: All patients presenting with BP-ONJ were treated with bone debridement of the affected area and multilayer wound closure. The considered variables were: gender, age, underlying diagnosis, type of bisphosphonate (BP) used, duration of bisphosphonate use, route of administration, location of the osteonecrosis, clinical symptoms, association with dental treatment and surgical outcome. RESULTS: Nineteen cases of a total of 21 demonstrated no recurrence of osteonecrosis during follow up (Mean 16 months - Range 12-24 months). One patient with a bilateral defect showed a dehiscence on one side and a small fistula on the contralateral side 6 weeks post-operatively and required revision surgery. Another patient developed a fistula after 4 weeks that was treated successfully with antibiotics and curettage. No patients had evidence of exposed bone, bland mucosa nor pain at the surgical site. CONCLUSION: The technique described can be recommended for patients with BP-ONJ if a conservative treatment fails.

Enterococcus faecalis affects the proliferation and differentiation of ovine osteoblast-like cells.

Enterococcus faecalis (E. faecalis) is a Gram-positive bacterium, mostly recovered from root-filled teeth with persistent periapical lesions. Bacterial contamination of root canals inevitably results in interaction between E. faecalis and periapical tissues during the dynamic process of periapical inflammation. This study investigated the impact of heat-inactivated endodontic E. faecalis on the proliferation and the differentiation of ovine osteoblast-like cells, in an attempt to elucidate its putative enhanced pathogenicity mechanisms. Therefore, two different concentrations of a heat-inactivated endodontic E. faecalis isolate (2 × 10(6) or 2 × 10(8) CFU/ml) were incubated with ovine osteoblast-like cells for 7 and 14 days, respectively. Cells without antigen served as control. The effects of antigen on cell growth were evaluated by a proliferation assay (EZ4U). Furthermore, the assessment of alkaline phosphatase (ALP) activity, calcium deposition, and osteocalcin (OCN) gene expression through quantitative real-time PCR determined the degree of osteogenic cell differentiation. Scanning electron microscopy (SEM) was also performed to detect alterations in cell morphology. Interestingly, although highly concentrated E. faecalis increased cellular reproduction after 14 days, ALP activity and OCN gene expression decreased in an antigen concentration-dependent and incubation time-independent way. SEM images revealed E. faecalis adhesion on cells, a fact that might contribute to its virulence. These results suggest that E. faecalis stimulated cell multiplication, whereas it likely restrained cell differentiation of ovine osteoblast-like cells. In conclusion, the presence of E. faecalis in root canals may negatively affect periapical new bone formation, and thus, the healing of periapical lesions.

Tissue-engineered polymer-based periosteal bone grafts for maxillary sinus augmentation: five-year clinical results.

PURPOSE: Augmentation of the maxillary sinus with allogenic or alloplastic materials, as well as autologous bone grafts, has inherent disadvantages. Therefore, the aim of our study was to evaluate the long-term clinical repair effect of autologous periosteal bone grafts on atrophic maxillary bone. PATIENTS AND METHODS: In the present retrospective cohort study, augmentation of the edentulous atrophic posterior maxilla was performed using autologous tissue-engineered periosteal bone grafts based on bioresorbable polymer scaffolds and, in a 1-step procedure, simultaneous insertion of dental implants. The clinical evaluation of 10 patients was performed by radiologic assessment of bone formation, with a follow-up of 5 years. Bone formation was further documented by measuring the bone height and by histologic examination. RESULTS: Excellent clinical and radiologic results were achieved as early as 4 months after transplantation of the periosteal bone grafts. The bone height remained significantly (P < .05) greater (median 14.2 mm) than the preoperative atrophic bone (median 6.9 mm) during the 5-year observation period. Histologically, the bone biopsy specimens of 2 patients obtained after 6 months showed trabecular bone with osteocytes and active osteoblasts. No signs of bone resorption, formation of connective tissue, or necrosis were seen. CONCLUSION: Our results suggest that the transplantation of autologous periosteal bone grafts and implantation of dental implants in a 1-step procedure is a reliable procedure that leads to bone formation in the edentulous posterior maxilla, remaining stable in the long term for a period of at least 5 years.

Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial--per-protocol analysis.

PURPOSE: The purpose of this work was to evaluate the potential of substituting autogenous bone (AB) by bone marrow aspirate concentrate (BMAC). Both AB and BMAC were tested in combination with a bovine bone mineral (BBM) for their ability of new bone formation (NBF) in a multicentric, randomized, controlled, clinical and histological noninferiority trial. MATERIALS AND METHODS: Forty-five severely atrophied maxillary sinus from 26 patients were evaluated in a partial cross-over design. As test arm, 34 sinus of 25 patients were augmented with BBM and BMAC containing mesenchymal stem cells. Eleven control sinus from 11 patients were augmented with a mixture of 70% BBM and 30% AB. Biopsies were obtained after a 3-4-month healing period at time of implant placement and histomorphometrically analyzed for NBF. RESULTS: NBF was 14.3%±1.8% for the control and nonsignificantly lower (12.6%±1.7%) for the test (90% confidence interval: -4.6 to 1.2). Values for BBM (31.3%±2.7%) were significantly higher for the test compared with control (19.3%±2.5%) (p<0.0001). Nonmineralized tissue was lower by 3.3% in the test compared with control (57.6%; p=0.137). CONCLUSIONS: NBF after 3-4 months is equivalent in sinus, augmented with BMAC and BBM or a mixture of AB and BBM. This technique could be an alternative for using autografts to stimulate bone formation.

Making bone II: maxillary sinus augmentation with mononuclear cells--case report with a new clinical method.

We report a simplified method of using bone marrow aspirate concentrate (BMAC™) to regenerate hard tissue. The results suggest that BMAC™ combined with a suitable biomaterial can form sufficient bone within 3 months for further implants to be inserted, and at the same time minimise morbidity at the donor site.