Neutrophil-like cells derived from the HL-60 cell-line as a genetically-tractable model for neutrophil degranulation.

Research on neutrophil biology has been limited by the short life span and limited genetic manipulability of these cells, driving the need for representative and efficient model cell lines. The promyelocytic cell line HL-60 and its subline PLB-985 can be differentiated into neutrophil-like cells (NLCs) and have been used to study neutrophil functions including chemotaxis, phagocytosis, endocytosis, and degranulation. Compared to neutrophils derived from hematopoietic stem cells, NLCs serve as a cost-effective neutrophil model. NLCs derived from both HL-60 and PLB-985 cells have been shown to perform degranulation, an important neutrophil function. However, no study has directly compared the two lines as models for degranulation including their release of different types of mobilizable organelles. Furthermore, Nutridoma, a commercially available supplement, has recently been shown to improve the chemotaxis, phagocytosis, and oxidative burst abilities of NLCs derived from promyelocytic cells, however it is unknown whether this reagent also improves the degranulation ability of NLCs. Here, we show that NLCs derived from both HL-60 and PLB-985 cells are capable of degranulating, with each showing markers for the release of multiple types of secretory organelles, including primary granules. We also show that differentiating HL-60 cells using Nutridoma does not enhance their degranulation activity over NLCs differentiated using Dimethyl Sulfoxide (DMSO) plus Granulocyte-colony stimulating factor (G-CSF). Finally, we show that promyelocytic cells can be genetically engineered and differentiated using these methods, to yield NLCs with a defect in degranulation. Our results indicate that both cell lines serve as effective models for investigating the mechanisms of neutrophil degranulation, which can advance our understanding of the roles of neutrophils in inflammation and immunity.

Signaling dynamics distinguish high- and low-priority neutrophil chemoattractant receptors.

Human neutrophils respond to multiple chemoattractants to guide their migration from the vasculature to sites of infection and injury, where they clear pathogens and amplify inflammation. To properly focus their responses during this complex navigation, neutrophils prioritize pathogen- and injury-derived signals over long-range inflammatory signals, such as the leukotriene LTB4, secreted by host cells. Different chemoattractants can also drive qualitatively different modes of migration even though their receptors couple to the same Gαi family of G proteins. Here, we used live-cell imaging to demonstrate that the responses differed in their signaling dynamics. Low-priority chemoattractants caused transient responses, whereas responses to high-priority chemoattractants were sustained. We observed this difference in both primary neutrophils and differentiated HL-60 cells, for downstream signaling mediated by Ca2+, a major regulator of secretion, and Cdc42, a primary regulator of polarity and cell steering. The rapid attenuation of Cdc42 activation in response to LTB4 depended on the phosphorylation sites Thr308 and Ser310 in the carboxyl-terminal tail of its receptor LTB4R in a manner independent of endocytosis. Mutation of these residues to alanine impaired chemoattractant prioritization, although it did not affect chemoattractant-dependent differences in migration persistence. Our results indicate that distinct temporal regulation of shared signaling pathways distinguishes between receptors and contributes to chemoattractant prioritization.

Alveolar bone remodeling in virtually planned, bone-grafted vs non-grafted guided flapless implant surgery in the anterior maxilla: a cross-sectional retrospective follow-up study.

PURPOSE: In patients who underwent virtual planning and guided flapless implant surgery for teeth missing in the anterior maxilla, we compared buccal bone loss between those treated with and without autogenous bone augmentation. METHODS: Of 22 patients with teeth missing because of trauma or aplasia, 10 (18 implant sites) were reconstructed with buccally placed bone graft harvested from the mandibular ramus, and 12 were non-reconstructed (16 sites). Baseline cone-beam computed tomography allowed for implant planning using the NobelClinician® software and was performed again at 1 year after functional loading. The marginal bone level was assessed radiographically at post-implant baseline and at follow-up. RESULTS: At follow-up, buccal bone loss differed significantly between groups at the central level of the implant (p = 0.0005) but not at the coronal level (p = 0.329). The mean marginal bone level change was 0.6 mm, with no significant between-group difference (p = 0.876). The actual implant position often deviated in the vertical or sagittal plane by an average of 0.3-0.6 mm from the planned position. CONCLUSION: Compared with non-reconstructed patients, reconstructed patients experienced significantly more buccal bone loss at the central level of implants. The groups did not differ at the coronal level or in marginal bone loss, possibly because of the more augmented bone at the central level among reconstructed patients. Differences between planned versus actual implant positions should be considered in situations of limited bone volume at the planned implant site.

Histone H3.3 G34 mutations promote aberrant PRC2 activity and drive tumor progression.

A high percentage of pediatric gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histone variant H3.3. We find that these H3.3 G34 mutations directly alter the enhancer chromatin landscape of mesenchymal stem cells by impeding methylation at lysine 36 on histone H3 (H3K36) by SETD2, but not by the NSD1/2 enzymes. The reduction of H3K36 methylation by G34 mutations promotes an aberrant gain of PRC2-mediated H3K27me2/3 and loss of H3K27ac at active enhancers containing SETD2 activity. This altered histone modification profile promotes a unique gene expression profile that supports enhanced tumor development in vivo. Our findings are mirrored in G34W-containing giant cell tumors of bone where patient-derived stromal cells exhibit gene expression profiles associated with early osteoblastic differentiation. Overall, we demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors.

H3 K27M and EZHIP Impede H3K27-Methylation Spreading by Inhibiting Allosterically Stimulated PRC2.

Diffuse midline gliomas and posterior fossa type A ependymomas contain the recurrent histone H3 lysine 27 (H3 K27M) mutation and express the H3 K27M-mimic EZHIP (CXorf67), respectively. H3 K27M and EZHIP are competitive inhibitors of Polycomb Repressive Complex 2 (PRC2) lysine methyltransferase activity. In vivo, these proteins reduce overall H3 lysine 27 trimethylation (H3K27me3) levels; however, residual peaks of H3K27me3 remain at CpG islands (CGIs) through an unknown mechanism. Here, we report that EZHIP and H3 K27M preferentially interact with PRC2 that is allosterically activated by H3K27me3 at CGIs and impede its spreading. Moreover, H3 K27M oncohistones reduce H3K27me3 in trans, independent of their incorporation into the chromatin. Although EZHIP is not found outside placental mammals, expression of human EZHIP reduces H3K27me3 in Drosophila melanogaster through a conserved mechanism. Our results provide mechanistic insights for the retention of residual H3K27me3 in tumors driven by H3 K27M and EZHIP.

Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase.

Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). Trimethylation at H3K27 (H3K27me3) is associated with transcriptional silencing of developmentally important genes. Intriguingly, H3K27me3 is mutually exclusive with H3K36 trimethylation on the same histone tail. Disruptions in this cross-talk result in aberrant H3K27/H3K36 methylation patterns and altered transcriptional profiles that have been implicated in tumorigenesis and other disease states. Despite their importance, the molecular details of how PRC2 "senses" H3K36 methylation are unclear. We demonstrate that PRC2 is activated in cis by the unmodified side chain of H3K36, and that this activation results in a fivefold increase in the kcat of its enzymatic activity catalyzing H3K27 methylation compared with activity on a substrate methylated at H3K36. Using a photo-cross-linking MS strategy and histone methyltransferase activity assays on PRC2 mutants, we find that EZH2 contains a specific sensing pocket for the H3K36 methylation state that allows the complex to distinguish between modified and unmodified H3K36 residues, altering enzymatic activity accordingly to preferentially methylate the unmodified nucleosome substrate. We also present evidence that this process may be disrupted in some cases of Weaver syndrome.

Clinical outcome and factors determining new bone formation in lateral sinus membrane elevation with simultaneous implant placement without grafting material: A cross-sectional, 3-17 year follow-up study.

BACKGROUND: Lateral sinus membrane elevation with simultaneous implant placement without grafting material (graft-less LSFE) is a widely investigated method for bone augmentation of the maxillary sinus floor. Long-term follow-up studies are rare. PURPOSE: This study aimed to investigate the long-term effects of implants placed with graft-less LSFE. MATERIALS AND METHODS: The study group was comprised of 111 patients previously treated with graft-less LSFE. The first follow-up visit, which occurred after a mean of 5 years after surgery, included a clinical examination, cone beam computerized tomography, and panorama or intraoral radiography. The second follow-up included panorama or intraoral radiography, and it was conducted after a mean of 8 years. RESULTS: Overall, 218 implants were placed in 127 sinuses. Nine of the 218 implants failed resulting in an overall implant survival of 95.9%. The average bone gain at the follow-up was 4.0 ±2.0 mm. CONCLUSION: The implant-supported rehabilitation achieved using graft-less LSFE was stable over time, and there was no or little impact on sinus health. Furthermore, it was concluded that the new bone formation and the amount of bone gain is proportional to the length of the implant protruding into the sinus cavity.

Sinus floor elevation procedures to enable implant placement and integration: techniques, biological aspects and clinical outcomes.

Implant treatment in an atrophied edentulous posterior maxilla constitutes a challenge for the therapeutic team. The authors of the present study acknowledge that modern micro-rough surface implants in lengths of about 8-10 mm or longer and of different brands are similarly successful. Consequently, the authors propose that the use of different sinus floor elevation techniques should be considered when < 8 mm of bone is available below the maxillary sinus. The type of sinus floor elevation technique selected is mainly based on residual vertical bone height, marginal bone width, local intrasinus anatomy and the number of teeth to be replaced, although other factors (such as surgical training and surgical experience) may have an impact. It is proposed that a transcrestal sinus floor elevation approach can be considered as a first-choice method for single tooth gaps in situations with sufficient width for implant placement and a residual bone height of 5-8 mm, while lateral sinus floor elevation, with or without grafting materials, is indicated when < 5 mm of bone is available and when several teeth are to be replaced. With regard to time of implant placement, a one-stage procedure is preferred provided that high primary stability can be ensured.

Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.

Several types of pediatric cancers reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. Here we report that the H3 lysine 36-to-methionine (H3K36M) mutation impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases. Depleting H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy the H3K36M mutation. After the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of its target genes known to block mesenchymal differentiation. Our findings are mirrored in human undifferentiated sarcomas in which novel K36M/I mutations in H3.1 are identified.

S-adenosyl methionine is necessary for inhibition of the methyltransferase G9a by the lysine 9 to methionine mutation on histone H3.

Lysine to methionine (K-to-M) mutations in genes encoding histone H3 are thought to drive a subset of pediatric brain and bone cancers. These high-frequency K-to-M mutations occur at sites of methylation on histone H3, and tumors containing the mutant histones exhibit a global loss of specific histone methylation marks. Previous studies showed that K-to-M mutant histones, also known as oncohistones, are potent orthosteric inhibitors of specific Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain methyltransferases. However, the biochemical and biophysical details of the interaction between K-to-M mutant histones and the respective SET domain methyltransferases are currently unknown. Here, we use the histone H3K9-directed methyltransferase G9a as a model to explore the mechanism of inhibition by K-to-M oncohistones. X-ray cocrystal structures revealed that the K9M residue of histone H3 occupies the active site cavity of G9a, and kinetic analysis indicates competitive inhibition of G9a by histone H3K9M. Additionally, we find that the cofactor S-adenosyl methionine (SAM) is necessary for stable interaction between G9a and H3K9M histone. Consistent with the formation of a ternary complex, we find that the inhibitory peptide is uncompetitive with regard to SAM. These data and others indicate that K-to-M oncohistones promote global loss of specific lysine methylation through sequestration and inhibition of SAM-bound SET domain methyltransferases.

On the Early Mechanisms of Bone Formation after Maxillary Sinus Membrane Elevation: An Experimental Histological and Immunohistochemical Study.

BACKGROUND: Previous studies have shown predictable bone formation in the maxillary sinus after membrane elevation. However, how and where the bone is formed is not well understood. PURPOSE: The aim of the study was to histologically and immunohistochemically study the early bone formation events in primates after membrane elevation in the maxillary sinus. MATERIALS AND METHODS: Nine adult male tufted capuchin primates (Cebus apella) were included in the study. Eight animals were subjected to bilateral maxillary sinus membrane elevation using a lateral replaceable bone window technique. One oxidized dental implant was placed into the maxillary sinus cavity on both sides. In four animals, one sinus was left without any additional treatment, whereas the contralateral sinus was filled with autologous bone grafts from the tibia. In two animals, the implants were inserted under the elevated sinus membrane on both sides. In two animals, the sinus membrane was totally removed. The animals were euthanized after 10 or 45 days. One nonoperated animal representing pristine tissue conditions served as control. The maxillary sinuses with implants were retrieved and further processed for light microscopic ground sections or decalcified sections for immune-histochemical analyses. RESULTS: Bone formation started from the bottom of the sinus floor, sprouting into the granulation tissue along the implant surface under the elevated membrane irrespective of time and surgical technique. Bone formation was not seen in direct conjunction with the sinus membrane. A distinct expression of osteopontin was observed in the serous glands of the lamina propria close to the implant within all groups. CONCLUSION: Bone formation after sinus membrane elevation with or without additional bone grafts starts at the sinus floor and sprouts into the elevated space along the implant surface. The sinus membrane does not seem to present osteoinductive potential in sinus membrane elevation procedures in this study.

Follow-up study of implants with turned or oxidized surfaces placed after sinus augmentation.

PURPOSE: To compare long-term survival and clinical outcomes of endosseous implants with different surface characteristics in patients with sinus elevation procedures, autologous bone grafting, and delayed implant placement. MATERIALS AND METHODS: Implant survival, peri-implant soft tissue conditions, marginal bone level, intrasinus apical bone level, and sinus health were studied in patients subjected to autologous bone graft and delayed placement of implants with turned or oxidized surfaces. After a minimum of 5 years of functional loading, all patients were clinically examined regarding gingival pocket depth (PD) and bleeding on probing (BoP). The marginal bone level (MBL) was measured in intraoral radiographs. Cone beam computed tomography was used to evaluate the apical bone level (ABL) of the implants and intrasinus conditions. RESULTS: Twenty-eight patients received sinus elevation and a total of 92 dental implants. Thirteen patients received 47 implants with a turned surface, and 15 patients received 45 implants with an oxidized surface. Mean follow-up was 10 years (range, 5 to 19 years). No significant difference was found between the two implant surfaces in terms of PD, BoP, MBL, or ABL. Four patients (14%) exhibited radiographic signs of sinus pathology, with opacification, polyp-like structures, and thickening of the sinus membrane. Radiographic signs of sinus pathology were not correlated to implant survival or to the investigated parameters. CONCLUSION: Grafting of the maxillary sinus floor with intraorally harvested bone and delayed placement of either turned or oxidized implants results in equally high long-term survival rates, stable marginal and apical bone levels, and good peri-implant soft tissue health.

Immediate loading of implants placed simultaneously with sinus membrane elevation in the posterior atrophic maxilla: a two-year follow-up study on 10 patients.

BACKGROUND: Clinical studies on immediate loading of implants in the posterior atrophic maxilla are rare. PURPOSE: The study aims to evaluate immediate loading of implants placed with sinus membrane elevation without additional grafting material for bone augmentation of the maxillary sinus floor. MATERIALS AND METHODS: The study group comprised of 10 patients in whom a total of 10 maxillary sinus floor augmentations were performed. A total of 21 dental implants (1 to 4) were inserted through the residual bone to protrude into the maxillary sinus under the elevated sinus membrane. The implant site was underprepared to improve primary stability. All the implants were inserted with a torque insertion no less than 20 Ncm. Implants were loaded immediately after surgery with a screw-retained temporary acrylic restoration. Intraoral X-rays were taken at implant insertion, after 6 months loading, and after 1st and 2nd year of loading. Resonance frequency analysis (RFA) was performed at the time of initial placement and after 6 months of functional loading. RESULTS: RFA after implant insertion gave an implant stability quotient (ISQ) level with a range from 62 to 72. All implants remained clinically stable during the follow-up period of 2 years. Radiography demonstrated on average 5.7 ± 3.4 mm of intrasinus new bone formation after 6 months of implant loading. RFA measurements showed ISQ mean values of 67 (range: 62-72) and 68 (range: 62-71) at placement and after 6 months of loading, respectively. CONCLUSION: Within the limits of this case series report, it is concluded that maxillary sinus membrane elevation with simultaneous placement and immediate loading of implants without the use of any additional grafting material shows predictable results after 2 years of functional loading. Moreover, evidence of intrasinus bone formation around the implants was found in all patients. Further studies are needed to study the influence of immediate loading on the mineralization of bone forming at dental implant sites.

A retrospective comparison of oxidized and turned implants with respect to implant survival, marginal bone level and peri-implant soft tissue conditions after at least 5 years in function.

BACKGROUND: Long-term clinical follow-up studies comparing different implant surfaces with regard to survival and marginal conditions are rare. OBJECTIVES: The objective of this study was to compare the clinical performance of turned and oxidized implants after more than 5 years of loading. MATERIAL AND METHODS: One hundred three patients (43 men, 60 women; mean age 67.4 years, range 32-90) previously treated with 287 implants (Nobel Biocare AB, Gothenburg, Sweden), 133 with turned surface (MKIII, Nobel Biocare AB) and 154 with an oxidized surface (MKIII, TiUnite, Nobel Biocare AB) were examined after at least 5 years of loading (mean 82 months, range 60-93 months). The implants had been used for support of single crowns (33 patients/36 implants), partial bridges (39 patients/103 implants), or full bridges (31 patients/148 implants) following an early loading protocol (14 patients /54 implants), a one-stage protocol (32 patients/59 implants) or a two-stage protocol (57 patients/174 implants). Clinical examinations of bleeding on probing (BoP) and pocket depth (PD) were performed. Intraoral radiographs were used for assessments of marginal bone levels (MBLs). RESULTS: Seven turned implants and one oxidized implant failed, giving overall cumulative survival rates of 94.7 and 99.4%, respectively. There were no differences for BoP scores (0.5 ± 0.7 vs 0.4 ± 0.6) and PD measurements (1.7 ± 0.8 mm vs 1.8 ± 1.0 mm) parameters when comparing turned and oxidized implants, respectively. The mean MBL was 1.8 ± 0.8 mm and 2.0 ± 0.9 mm for turned and oxidized implants, respectively, after more than 5 years in function (NS). Frequency distribution of MBL loss showed no statistically significant differences between the two surfaces. A total of four implants (1.4%) (three oxidized and one turned) showed a PD > 3 mm, MBL > 4 mm, and BoP. However, none of these were associated with suppuration on examination. CONCLUSION: The present study does not state any differences in implant failure, MBL, presence of bleeding or PD around implants when comparing turned and oxidized titanium implants after at least 5 years of function.

Bone graft healing in reconstruction of maxillary atrophy.

PURPOSE: Evaluate correlations between volume change for iliac crest bone grafts in maxillary reconstruction (graft volume change [GVC]) and bone mineral density (BMD), bone volume fraction (BVF), hematologic bone metabolic factors (I), and identify indicators of implant failure (II). MATERIAL AND METHODS: Forty-six consecutive patients had their edentulous atrophic maxilla reconstructed with free autogenous bone grafts from anterior iliac crest. Endosteal implants were placed 6 months after graft healing. Computer tomography was performed after 3 weeks and 6 months after grafting. Bone biopsies were taken from the internal table of donor site for calculation (BVF), and blood samples were collected. Implant stability was measured at placement with resonance frequency analysis and expressed as implant stability quotient (ISQ). Implant failure was registered. RESULTS: GVC in onlay bone graft was 37%. The BVF in iliac crest biopsies was 32%. Serum-IGFBP3 differed with 79% of the samples over normal range. Fifteen patients had one or more implant failures prior to loading (early failures). Forty-two patients were followed for a minimum of 3 years after implant loading and, in addition, 6/42 patients had one or more implants removed during the follow-up (late failures). GVC correlated to decreased BMD of lumbar vertebrae L2-L4 (Kruskal-Wallis test, p=.017). No correlation was found between GVC and hematologic factors (Pearson correlation test) or between GVC and BVF (Kruskal-Wallis test). No correlation was found between ISQ and GVC (Pearson correlation test, p=.865). The association between implant failures and the described factors were evaluated, and no significant correlations were found (unconditional logistic regression). CONCLUSION: Onlay bone grafts decrease 37% during initial healing period, which correlate to BMD of lumbar vertebrae L2-L4. No other evaluated parameters could explain GVC. The evaluated factors could not explain implant failure.

Sinus bone formation and implant survival after sinus membrane elevation and implant placement: a 1- to 6-year follow-up study.

OBJECTIVES: To investigate the long-term clinical and radiographic results of the maxillary sinus membrane elevation technique where implants were inserted in a void space created by the elevation of the sinus membrane without adding any graft material. MATERIALS AND METHODS: A total of 84 patients were subjected to 96 membrane elevation procedures and simultaneous placement of 239 implants. Changes of intra-sinus and marginal bone height in relation to the implants were measured in intraoral radiographs taken at insertion, after 6 months of healing, after 6 months of loading and then annually. Computerized tomography was performed pre-surgically and 6 months post-surgically. Resonance Frequency Analyses measurements were performed at the time of implants placement, at abutment connection and after 6 months of loading. The implant follow-up period ranged from a minimum of one to a maximum of 6 years after implants loading. RESULTS: All implants were stable after 6 months of healing. A total of three implants were lost during the follow-up period giving a survival rate of 98.7%. Radiography demonstrated on average 5.3±2.1 mm of intra-sinus new bone formation after 6 months of healing. RFA measurements showed adequate primary stability (implant stability quotient 67.4±6.1) and small changes over time. CONCLUSION: Maxillary sinus membrane elevation and simultaneous placement of implants without the use of bone grafts or bone substitutes result in predictable bone formation with a high implant survival rate of 98.7% during a follow-up period of up to 6 years. The intra-sinus bone formation remained stable in the long-term follow-up. It is suggested that the secluded compartment allowed for bone formation according to the principle of guided tissue regeneration. The high implant survival rate of 98.7% indicated that the implants sufficiently supported the fixed bridges throughout the study period. This technique reduces the risks for morbidity related to harvesting of bone grafts and eliminates the costs of grafting materials.

Histological outcomes on the development of new space-making devices for maxillary sinus floor augmentation.

BACKGROUND: Previous studies have pointed out that the mere elevation of the maxillary sinus membrane promotes bone formation without the use of augmentation materials. PURPOSE: This experimental study aimed at evaluating if the two-stage procedure for sinus floor augmentation could benefit from the use of a space-making device in order to increase the bone volume to enable later implant installation with good primary stability. MATERIALS AND METHODS: Six male tufted capuchin primates (Cebus apella) were subjected to extraction of the three premolars and the first molar on both sides of the maxilla to create an edentulous area. The sinuses were opened using the lateral bone-wall window technique, and the membrane was elevated. One resorbable space-making device was inserted in each maxillary sinus, and the bone window was returned in place. The animals were euthanatized after 6 months, and biopsy blocks containing the whole maxillary sinus and surrounding soft tissues were prepared for ground sections. RESULTS: The histological examination of the specimens showed bone formation in contact with both the schneiderian membrane and the device in most cases even when the device was displaced. The process of bone formation indicates that this technique is potentially useful for two-stage sinus floor augmentation. The lack of stabilization of the device within the sinus demands further improvement of space-makers for predictable bone augmentation. CONCLUSIONS: It is concluded that (1) the device used in this study did not trigger any important inflammatory reaction; (2) when the sinus membrane was elevated, bone formation was a constant finding; and (3) an ideal space-making device should be stable and elevate the membrane to ensure a maintained connection between the membrane and the secluded space.

Histological findings following the use of a space-making device for bone reformation and implant integration in the maxillary sinus of primates.

BACKGROUND: Previous studies have shown that membrane elevation results in predictable bone formation in the maxillary sinus provided that implants can be placed as tent poles. In situations with an extremely thin residual crest which impairs implant placement, it is possible that a space-making device can be used under the sinus membrane to promote bone formation prior to placement of implants. PURPOSE: The present study was conducted to test the hypothesis that the use of a space-making device for elevation of the sinus membrane will result in predictable bone formation at the maxillary sinus floor to allow placement of dental implants. MATERIALS AND METHODS: Eight tufted capuchin primates underwent bilateral sinus membrane elevation surgery, and a bioresorbable space-making device, about 6 mm wide and 6 mm in height, was placed below the elevated membrane on the sinus floor. An oxidized implant (Nobel Biocare AB, Gothenburg, Sweden) was installed in the residual bone protruding into the created space at one side while the other side was left without an implant. Four animals were sacrificed after 6 months of healing. The remaining four animals received a second implant in the side with a space-making device only and followed for another 3 months before sacrifice. Implant stability was assessed through resonance frequency analysis (RFA) using the Osstell (Osstell AB, Gothenburg, Sweden) at installation, 6 months and 9 months after the first surgery. The bone-implant contact (BIC) and bone area inside the threads (BA) were histometrically evaluated in ground sections. RESULTS: Histologically there were only minor or no signs of bone formation in the sites with a space-making device only. Sites with simultaneous implant placement showed bone formation along the implant surface. Sites with delayed implant placement showed minor or no bone formation and/or formation of a dense fibrous tissue along the apical part of the implant surface. In the latter group the apical part of the implant was not covered with the membrane but protruded into the sinus cavity. CONCLUSIONS: The use of a space-making device, with the design used in the present study, does not result in bone formation at the sinus floor. However, membrane elevation and simultaneous placement of the device and an implant does result in bone formation at the implant surface while sites with implants placed 6 months after membrane elevation show only small amounts of bone formation. It is suggested that lack of stabilization of the device and/or a too extensive elevation of the membrane may explain the results.