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Aim: This bibliometric study analyzed the characteristics of the 100 most cited articles on bone grafts in dentistry. Materials and Methods: A database search was performed on the Web of Science Core Collection using a specific search strategy. Scopus and Google Scholar were also consulted for citation comparisons. Data extracted included: title, citation metrics, publication year, journal, study design, graft material, surgical technique, authors, institution, and country. Bibliometric networks were generated using VOSviewer. Results: The identified articles were published between 1991 and 2019. Citation counts ranged from 120 to 1161 (mean: 240, 30). Clinical Oral Implants Research was the most cited journal (5175 citations; 25/100). Xenogeneic bone graft material was the most frequently used (5130 citations; 22/100). Europe had 62 articles (14,604 citations), and the United States was the most prominent country (5209 citations; 22/100). The University of Bern had the highest number of citations (2565 citations; 13/100), with Buser D as the author with the largest number of articles (2648 citations; 12/100). Conclusion: This study shows the scientific progress on bone grafts in dentistry. The use of xenogeneic grafts for horizontal and/or vertical ridge augmentation was the most prominent trend. [ABSTRACT FROM AUTHOR]

Objectives: To gauge the relative accuracy of the use of passive and active dynamic navigation systems when placing dental implants, and to determine how registration areas affect the performance of these systems., Materials and Methods: Eighty implants were assigned to be placed into 40 total resin mandible models missing either the left or right first molars using either passive or active dynamic navigation system approaches. U-shaped tube registration devices were fixed in the edentulous site for 20 models each on the left or right side. Planned and actual implant positions were superimposed to assess procedural accuracy, and parameters including 3D entry deviation, angular deviation, and 3D apex deviation were evaluated with Mann-Whitney U tests and Wilcoxon signed-rank tests., Results: Respective angular, entry, and apex deviation values of 1.563 ± 0.977°, 0.725 ± 0.268 mm, and 0.808 ± 0.284 mm were calculated for all included implants, with corresponding values of 1.388 ± 1.090°, 0.789 ± 0.285 mm, and 0.846 ± 0.301 mm in the active group and 1.739 ± 0.826°, 0.661 ± 0.236 mm, and 0.769 ± 0.264 mm in the passive group. Only angular deviation differed significantly among groups, and the registration area was not associated with any significant differences among groups., Conclusions: Passive and active dynamic navigation approaches can achieve comparable in vitro accuracy. Registration on one side of the missing single posterior tooth area in the mandible can complete single-tooth implantation on both sides of the posterior teeth, highlighting the promise of further clinical research focused on this topic., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To assess the relative accuracy of manual (U‐shaped tube) and automatic (two‐in‐one) dynamic navigation registration techniques for implant surgery performed in posterior sites missing one tooth. Materials and Methods: This study included 58 partially edentulous patients with 58 implants, including 31 and 27 in the manual and automatic groups. Deviations between the planned and actual implant placement were assessed. Results: The angular deviation in the overall study cohort was 2.54 ± 1.21°, while the 3D deviations at the implant platform and apex were 0.90 ± 0.46 mm and 1.04 ± 0.47 mm, respectively. The respective angular deviations in the manual and automatic groups were 2.82 ± 1.17° and 2.21 ± 1.19° (p >.05), while platform deviations were 0.89 ± 0.48 mm and 0.91 ± 0.45 mm (p >.05), and apex deviations were 0.99 ± 0.48 mm and 1.11 ± 0.46 mm (p >.05). No significant differences in absolute buccolingual, mesiodistal, or apicocoronal deviations were detected between these groups at either level (p >.05) nor were did deviation distributions differ in the buccolingual, mesiodistal, or apicocoronal directions at the platform or apex levels (p >.05). Conclusions: Manual and automatic dynamic navigation registration techniques can achieve excellent accuracy when placing implants in posterior sites missing a single tooth. The two‐in‐one automatic registration technique can reduce the amount of time and intraoperative steps necessary to complete the registration process relative to the manual U‐shaped tube registration technique. Further follow‐up studies are necessary to expand on these results. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy of dynamic computer-aided surgery (dCAS) in replacing a single missing posterior tooth, we compare outcomes when using registration-and-fixation devices positioned anterior or posterior to the surgical site. Registration is performed on either the anterior or opposite posterior teeth., Methods: Forty individuals needing posterior single-tooth implant placement were randomly assigned to anterior or posterior registration. Nine parameters were analyzed to detect the deviations between planned and actual implant placement, using Mann-Whitney and t-tests for nonnormally and normally distributed data, respectively., Results: The overall average angular deviation for this study was 2.08 ± 1.12°, with the respective average 3D platform and apex deviations of 0.77 ± 0.32 mm and 0.88 ± 0.32 mm. Angular deviation values for individuals in the anterior and posterior registration groups were 1.58°(IQR: 0.98°-2.38°) and 2.25°(IQR: 1.46°-3.43°), respectively (p = .165), with 3D platform deviations of 0.81 ± 0.29 mm and 0.74 ± 0.36 mm (p = .464), as well as 3D apex deviations of 0.89 ± 0.32 mm and 0.88 ± 0.33 mm (p = .986). No significant variations in absolute buccolingual (platform, p = .659; apex, p = .063), apicocoronal (platform, p = .671; apex, p = .649), or mesiodistal (platform, p = .134; apex, p = .355) deviations were observed at either analyzed levels., Conclusions: Both anterior and posterior registration approaches facilitate accurate dCAS-mediated implant placement for single missing posterior teeth. The device's placement (posterior-to or anterior-to the surgical site) did not affect the clinician's ability to achieve the planned implant location., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this meta‐analysis was to compare implant survival in irradiated and non‐irradiated bone and to investigate potential risk factors for implant therapy in oral cancer patients. Material and methods: An extensive search in the electronic databases of the National Library of Medicine was performed. Systematic review and meta‐analysis were conducted according to PRISMA statement. The meta‐analysis was performed for studies with a mean follow‐up of at least three and five years, respectively. Results: The systematic review resulted in a mean overall implant survival of 87.8% (34%–100%). The meta‐analysis revealed a significantly higher rate of implant failure in irradiated bone compared to non‐irradiated bone (p <.00001, OR 1.97, CI [1.63, 2.37]). The studies also showed that implants placed into irradiated grafted bone were more likely to fail than those in irradiated native bone (p <.0001, OR 2.26, CI [1.50, 3.40]). Conclusion: Even though overall implant survival was high, radiotherapy proves to be a significant risk factor for implant loss. Augmentation procedures may also increase the risk of an adverse outcome, especially in combination with radiotherapy. Clinical relevance: The treatment of patients receiving radiotherapy of any form requires precise individual planning and a close aftercare. Implants should be placed in local bone rather than in bone grafts, if possible. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate clinical, radiological performance of novel digital workflow integrating dynamic navigation to streamline in one-visit single-implant immediate loading in aesthetic zone. Material and methods: Consecutive patients requiring one single-implant in aesthetic zone of both jaws were treated between May and September 2017. Primary outcomes were implant and prosthetic success rates, surgical and prosthetic complications, marginal bone loss (MBL), final pink aesthetic score (PES-f), and implant stability quotient (ISQ-f). Secondary outcomes were ISQ-0 and PES-0 at implant positioning and PES-p at definitive prosthesis placement. Potential effect of jaw (maxilla vs mandible), biotype (thin vs thick), type of incision (flap vs flapless), and implant site (healed vs. post-extractive) on the primary outcomes (MBL, PES-f, and ISQ-f) was evaluated through a multivariable analysis. Results: Fifty-two implants were placed (follow-up 18.6, 15-20 months). One post-extractive implant failed. No other surgical, biological complications occurred, accounting for 98.10% cumulative success rate (CSR). No definitive prostheses failed. Mean MBL was -0.63 ± 0.25 mm (-1.69 to -0.06). PES-f was 12.34 ± 1.41 (9-14). ISQ-f was 78.1 ± 3.2 (70-84). Age had significantly negative effect on MBL and PES-f (p = .0058 and p = .0052). No other variables significantly affected primary outcomes. Conclusions: Within study limitations, investigated digital workflow integrating dynamic navigation was reliable for single-implant immediate loading in aesthetic zone in one visit. No statistically significant difference was found for MBL, PES-f, and ISQ-f, considering type of incision (flap vs. flapless), implant site (healed vs post-extractive), jaw (maxilla vs. mandible), and biotype (thick vs. thin). Live-tracked dynamic navigation may have contributed to improve operator clinical performance regardless of implant site characteristics. Further investigations are needed to confirm positive outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This critical review is aimed to investigate the current status of qualitative research in dental implant research and to explore the quality of available information. Material and methods: A systematic search was done on the journal databases to identify dental implant research articles that used qualitative methodology during 2006 and 2020. The resulting articles were appraised against the checklist offered by the Critical Appraisal Skills programme (CASP) tool. Also, the theories evolved from the research were reviewed to understand the value of this methodology in dental implant research. Results: Twenty‐five (25) articles out of the 8,421 original results were identified as using qualitative methodology. The researchers have sought to identify the views of patients about tooth loss, dental implants, and the information they receive from dental professionals, and views of the dentists about dental implant practice. The review found that there were few inconsistencies in the quality of such research especially the qualitative data analysis. Conclusions: The quantity of qualitative research in dental implants remains low; however, the quality has improved in the past two decades. Despite these improvements, there is still a lack of research in understanding both patients' and dentists' views on dental implant procedures and management. [ABSTRACT FROM AUTHOR]

Objective: To assess clinical and patient‐reported outcomes of implant‐prosthetic rehabilitations in patients with a history of head–neck cancer (HNC), treated with tumor resection without (TR) or with adjuvant radiotherapy (TR/RT). A healthy cohort rehabilitated with the same reconstructive protocols served as control group (C). Materials and Methods: A total of 28 women and 29 men were considered in the present retrospective study. Participants received 322 implants, finally supporting 79 prosthetic reconstructions. Primary outcome was the assessment of implant and prosthetic survival rates. Furthermore peri‐implant soft tissue parameters (attached peri‐implant mucosa, AM; modified bleeding and plaque indices, mBI/mPI; probing depth, PD) and prosthetic technical complications were documented. Patient‐reported outcome measures (PROMs) by means of visual analog scales (VAS) and the Oral Health Impact Profile German 14 form (OHIP G14) were collected. For statistical purposes Chi‐square and Mann–Whitney‐U‐Test were adapted. Results: After a mean follow‐up of 81.2 ± 50.3 months, implant survival rate was 98.1% (HNC‐TR), 98.2% (HNC‐TR/RT) and 100.0% (C), respectively (four implants failed in the HNC groups). HNC‐TR/RT showed significant higher mPI and mBI compared to C. Within HNC‐TR/RT, vestibuloplasty significantly reduced mBI and PD values. No failures occurred at the prosthetic level. Overall, higher VAS scores were reported for bar‐ compared with Locator‐retained prostheses. Furthermore, increased OHIP G14 values resulted for HNC‐TR/RT. Conclusions: High survival rates on implant and prosthetic level were observed. The use of soft tissue grafts resulted in stabilization of the peri‐implant mucosa in irradiated patients. In terms of retention and chewing ability, participants preferred bars over Locator attachments. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present randomized, controlled clinical multicenter trial was to compare a polyethylene glycol (PEG) and a native collagen membrane (BG) for simultaneous guided bone regeneration at bony dehiscence‐type defects around bone level titanium implants. Material and methods: The study enrolled 117 patients requiring implant treatment in the posterior maxilla or mandible with expected buccal bony dehiscence‐type defects at the placed titanium implants. According to a parallel groups design, defects were filled with a synthetic bone filler and randomly assigned to either PEG or BG membrane. As primary parameter, the relative vertical bone fill was assessed at baseline and at re‐entry after 6 months of healing. As secondary parameters, the marginal bone level (MBL) was assessed radiographically and soft tissue conditions were recorded up to 18 months postloading. Results: Both groups showed comparable vertical bone fill revealing a relative change in defect height of 59.7% (PEG) and 64.4% (BG). The absolute mean reduction in defect size was 2.5 mm in the PEG group and 3.2 mm in the BG group. Although both groups revealed a statistically significant mean defect reduction (p <.001), a comparison between the two groups did not show statistical significances. The non‐inferiority test with inferiority limit of −5% could not be rejected, based on the 90% confidence interval of the differences of the two means with lower limit −15.4%. After 18 months, an MBL increase of 0.45 ± 0.43 mm in the PEG group and 0.41 ± 0.81 mm in the BG group was detected (p <.001). Soft tissue complications were observed in both groups without showing statistical significance. Conclusions: Both membranes supported bone regeneration at dehiscence‐type defects and obtained vertical bone fill with a relative change in defect height of 59.7% (PEG) and 64.4% (BG); however, the non‐inferiority of PEG could not be shown. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this randomized controlled trial was to compare alveolar ridge preservation using a bone substitute material and covered with a synthetic or porcine collagen membrane. Materials and methods: Thirty‐two sockets in the aesthetic maxillary region of 30 patients were randomized into two groups. Randomization was stratified according to bone wall defect. Flapless technique was used, and sockets were grafted with bi‐phasic calcium phosphate particulate bone substitute and covered by synthetic polyethylene glycol (PEG; test group) or porcine‐derived collagen membrane (CM; control group). No primary closure was attempted. A cone beam computed tomography (CBCT) scan was performed immediately after the surgical procedure and repeated 22 weeks later. OnDemand3D was used to superimpose scan images and assess changes. The mean vertical and horizontal percentage bone loss were calculated and implants placed after 6 months with or without additional augmentation. Results: There were no baseline differences between groups or dropouts. The mean percentage loss at the labial plate and at the coronal part of the sockets was statistically significantly lower in the test group compared with controls (−2.86% [SD = 13.48] versus 7.42% [SD = 11.95]; 13.45% [SD = 11.97] versus 28.59% [SD = 16.97]). Implants were placed after 6 months, and there was no difference in need for further augmentation between PEG (n = 5) or CM (n = 4). Conclusion: Sites treated with PEG membrane showed less percentage loss in horizontal and vertical measurements in this trial. [ABSTRACT FROM AUTHOR]

Objectives: Recently, a new liquid carrier system for enamel matrix derivate (EMD‐liquid) was developed with better physico‐chemical properties for improved adsorption of EMD to biomaterial surfaces. The aim of the present study was to investigate the bone regenerative potential of EMD‐liquid in combination with a natural bone mineral (NBM) in vivo. Methods: Four 6‐mm defects were created in the calvaria of six New Zealand white rabbits. Defects were filled with either (1) control (empty), (2) 20 mg of NBM, or (3) 20 mg of NBM + 20 µl of EMD‐liquid (n = 8). All defects were covered with collagen barrier membranes. The bone regenerative potential was investigated by micro‐CT and histomorphological analyses at 8 weeks postsurgery. Results: The mineralized tissue volume was significantly higher in the NBM + EMD‐liquid group when compared to control, whereas no difference was observed between the NBM alone and control groups. While no significant difference was observed for horizontal bone defect closure between the NBM + EMD‐liquid and the NBM alone groups, NBM + EMD‐liquid significantly increased the total mineralized area and reduced the percentage of soft/connective tissue infiltration. No statistically significant difference was observed between the NBM + EMD‐liquid group and NBM alone group for amount of mineralized bone. Conclusion: The addition of EMD‐liquid did not lead to statistically significant bone formation when compared to NBM alone. The combination of NBM + EMD‐liquid but not NBM alone did however induce superior mineralized tissues when compared to control (empty). Further research investigating the adsorption potential of EMD‐liquid to bone‐grafting particles with/without collagen may provide valuable insights into future regenerative strategies with enamel matrix proteins. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this RCT was to compare the accuracy of implant placement between static and dynamic computer‐assisted implant surgery (CAIS) systems in single tooth space. Materials and methods: A total of 60 patients in need of a single implant were randomly assigned to two CAIS groups (Static n = 30, Dynamic n = 30) and implants were placed by one surgeon. Preoperative CBCT was transferred to implant planning software to plan the optimal implant position. Implants were placed using either stereolithographic guide template (Static CAIS) or implant navigation system (Dynamic CAIS). Postoperative CBCT was imported to implant planning software, and deviation analysis with the planned position was performed. Primary outcomes were the deviation measurements at implant platform, apex, and angle of placement. Secondary outcome was the distribution of the implant deviation into each 3D direction. Results: The mean deviation at implant platform and implant apex in the static CAIS group was 0.97 ± 0.44 mm and 1.28 ± 0.46 mm, while that in the dynamic CAIS group was 1.05 ± 0.44 mm and 1.29 ± 0.50 mm, respectively. The angular deviation in static and dynamic CAIS group was 2.84 ± 1.71 degrees and 3.06 ± 1.37 degrees. None of the above differences between the two groups reached statistical significance. The deviation of implants toward the mesial direction in dynamic CAIS group was significantly higher than that of the static CAIS (p = 0.032). Conclusions: Implant placement accuracy in single tooth space using dynamic CAIS appear to be the same to that of static CAIS. (Thai Clinical Trials Registry TCTR20180826001). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the molecular events in implant‐adherent cells and in peri‐implant bone during the osseointegration of machined and oxidized titanium implants in smokers and nonsmokers. Materials and Methods: Twenty‐four smokers and 24 nonsmokers each received machined and anodically oxidized mini‐implants. The mini‐implants and the surrounding bone were retrieved after 1, 7, and 28 days, for gene expression analysis of selected factors using quantitative polymerase chain reaction (qPCR). Results: Differences between machined and oxidized implants were more evident in the implant‐adherent cells than the peri‐implant bone. The machined implants revealed higher expression of proinflammatory cytokines, interleukin‐8 (IL‐8) (in nonsmokers), and tumor necrosis factor‐alpha (in nonsmokers and smokers), compared with the oxidized implants. Conversely, the expression of bone formation genes, alkaline phosphatase and osteocalcin, was generally higher at the oxidized implants. In smokers, the temporal pattern revealed the delayed and initial inhibition of osteoblastic and osteoclastic gene expression, respectively, mainly at the machined implants. In contrast, oxidized implants revealed higher expression of bone remodeling, cathepsin K (CatK) and calcitonin receptor, and coupling, receptor activator of nuclear factor kappa‐B ligand (RANKL) and osteoprotegerin, genes after 7 day in smokers. Conclusions: The implant‐adherent cells are more sensitive to surface properties and smoking conditions than the cells in the peri‐implant bone. Smoking imposes inhibitory effects on the initial molecular events of osseointegration in the human bone–implant interface. The surface properties of oxidized implants appear to have a beneficial effect on osseointegration by mitigating the smoking‐induced negative effects. [ABSTRACT FROM AUTHOR]

Aims: To perform a systematic literature review of the regenerative potential of bone substitutes used to fill critical size defects (CSDs) in rabbit calvariae; to determine the quality of the included studies using ARRIVE guidelines. Material and methods: An Internet search was performed in duplicate using MEDLINE, PubMed and Google Scholar databases (without restrictions on publication date) for studies reporting the regenerative potential of bone substitutes in CSDs in rabbit calvariae. Four parameters were analyzed by histomorphometry: new bone formation (NB); defect closure (DC); residual graft (RG); and connective tissue (CT). Animal Research Reporting in In Vivo Experiments (ARRIVE) guidelines (a list of 20 aspects for scoring texts and ensuring comparison between different experimental studies in animals) were used to evaluate the quality of the selected works. Results: Twenty‐one manuscripts were included. CSDs with 15 mm were predominant (57.14%). Only one study described the four histomorphometric parameters. NB formation was analyzed in 15 studies (71.42%) and was higher for particulate autogenous bone grafts (range 52.1–82%) after 12 weeks. DC was evaluated in six studies (28.57%) and was higher for fragmented adipose tissue grafts (range 53.33–93.33%) after 12 weeks. RG was evaluated in four studies (19.04%) and was higher for hydroxyapatite/beta‐tricalcium phosphate grafts with silica (HA/ß‐TCP + Si) (range 35.78–47.54%) at 12 weeks. CT was evaluated in two studies (9.5%) and was higher for HA/ß‐TCP + membrane (44.2%) at 12 weeks. Quality evaluation identified three items (title, introduction/objectives and experimental procedure) (15%) with excellent scores, 10 items (abstract, introduction/background, methods/ethical statement, experimental animals, experimental outcomes, statistics, results/baseline data, outcome/estimation and discussion interpretation/scientific implications) (50%) with average scores, and seven items (housing and husbandry, sample size, allocation, numbers analyzed, adverse effects, general applicability/relevance and funding) (35%) obtained poor scores. Only one manuscript obtained a quality evaluation considered as excellent. Conclusions: Autogenous bone grafts increase NB. DC is enhanced by the use of fragmented adipose tissue. RG remains in the defect for longer when hydroxyapatite/beta‐tricalcium phosphate with silica is used, and more CT can be expected when hydroxyapatite/beta‐tricalcium phosphate with silica grafts are covered by a membrane. The addition of stem cells of different origins to grafting materials enhances bone formation in early healing periods. The ARRIVE guidelines are still insufficiently used and the overall quality of studies remains low. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The objective of this study was to determine the effect of bone morphogenetic protein‐2 (BMP‐2) mixed with either polyethylene glycol hydrogel or synthetic bone substitute (SBS) on new bone formation in peri‐implant dehiscence defects after 16 weeks of healing. Materials and methods: A guided bone regeneration procedure was performed in box‐type peri‐implant defects that were surgically prepared in six beagle dogs. The following four experimental groups were used (i) control (no graft), (ii) SBS+hydrogel, (iii) SBS+BMP‐2/hydrogel and (iv) BMP‐2/SBS+hydrogel. Volumetric analysis using micro‐computed tomography and histomorphometric analysis was performed at 16 weeks post‐operatively. Results: The amount of new bone and the total augmented volume did not differ significantly between both BMP‐treated groups and the SBS+hydrogel group (p > .05). Likewise, no histometric differences were observed in the values of new bone area and bone‐to‐implant contact ratio among the three augmentation groups (new bone area: 0.06 ± 0.08, 0.19 ± 0.20, 0.48 ± 0.37 and 0.56 ± 0.60 mm2 [mean ± standard deviation] in groups 1–4, respectively; bone‐to‐implant contact: 9.44 ± 11.51%, 19.91 ± 15.19%, 46.31 ± 29.82% and 42.58 ± 26.27% in groups 1–4, respectively). Conclusion: The osteogenic efficacy of BMP‐2 on the regeneration of peri‐implant bone defects was not detectable after 16 weeks regardless of the carrier materials. [ABSTRACT FROM AUTHOR]

Objectives To test whether or not chemical and/or physical modifications of polyethylene glycol ( PEG) hydrogels influence degradation time, matrix/membrane stability, and integration into surrounding hard and soft tissues. Material and methods In 28 rabbits, six treatment modalities were randomly applied to six sites on the rabbit skull: a dense network PEG hydrogel ( PEG HD), a medium-dense network PEG hydrogel ( PEG MD), a medium-dense network PEG hydrogel modified with an RGD sequence ( PEG MD/ RGD), a medium-dense network PEG hydrogel modified with RGD with reduced carboxymethyl cellulose ( PEG MD/ RGD_ LV), a loose network PEG hydrogel modified with RGD ( PEG LD/ RGD), and a collagen membrane ( BG). Descriptive histology and histomorphometry were performed at 1, 2, 4, and 6 weeks. Results PEG HD revealed the highest percentage of residual matrix at all time points starting with 47.2% (95% CI: 32.8-63.8%) at 1 week and ending with 23.4% (95% CI: 10.3-49.8%) at 6 weeks. The hydrogel with the loosest network ( PEG LD/ RGD) was stable the first 2 weeks and then degraded continuously with a final area of 8.3% (95% CI: 3.2-21.2%). PEG HD was the most stable and densely stained membrane, whereas PEG MD and PEG LD matrices integrated faster, but started to degrade to a higher degree between 2 and 4 weeks. PEG MD degradation was dependent on the addition of RGD and the amount of CMC. Conclusions Chemical and/or physical modifications of PEG hydrogels influenced matrix stability. PEG MD/ RGD demonstrated an optimal balance between degradation time and integration into the surrounding soft and hard tissues. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. Material and methods In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/ TCP mixed with a synthetic PEG hydrogel, ii)HA/ TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/ TCP covered with a native collagen membrane ( CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro- CT and histological analyses were performed. Results Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. Conclusions Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect. [ABSTRACT FROM AUTHOR]

Objectives Biphasic calcium phosphate ( BCP) composed of 10% hydroxyapatite ( HA) and 90% beta-tricalcium phosphate has been developed. Recently, a strontium hydroxyapatite-containing collagen membrane ( Sr) was shown to stimulate early bone formation in rat calvarial defects at 4 weeks postoperatively, as compared with a cross-linked collagen membrane, for guided bone regeneration ( GBR). The objective of this study was to evaluate these novel biomaterials for GBR in relation to a non-cross-linked collagen membrane ( BG) and deproteinized bovine bone mineral ( BO). Materials and methods Twenty New Zealand rabbits were used in this study. Four defects of 7 mm in diameter were created in each rabbit, and three of the defects were treated with BG/ BO, Sr/ BO, and Sr/ BCP. Ten rabbits were sacrificed at 12 and 24 weeks, respectively. Histological and histomorphometric analyses were conducted. Volumetric densities of mineralized new bone ( MNB), bone marrow ( BM), residual grafting material ( RG), and non-mineralized connective tissue ( NCT) were determined for each group. Results After 12 weeks, Sr/ BCP yielded more MNB than BG/ BO and Sr/ BO with no significant difference among the three groups. After 24 weeks, however, Sr/ BCP demonstrated significantly more MNB than BG/ BO and Sr/ BO. Both after 12 and 24 weeks, Sr/ BCP showed significantly less RG than BG/ BO and Sr/ BO. There was a significant increase in MNB in Sr/ BCP from 12 to 24 weeks. Conclusions In defects grafted with BCP, more MNB was formed while less RG remained, than in defects grafted with BO. The Sr membrane was as effective as BG when comparing Sr/ BO with BG/ BO. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate guided bone regeneration outcomes in defects protected with an in situ formed polyethylene glycol (PEG) hydrogel membrane as compared to a non-cross-linked collagen membrane (CM). Material and methods: Four mandibular alveolar ridge defects were created in eight hound dogs. Regenerative procedures were randomly allocated to one of four groups consisting of freeze-dried bone allograft, which is referred to in this study as freeze-dried bone xenograft (FDBX) + PEG, autogenous bone (AB) + PEG, AB + CM, and AB alone. After 8 weeks, titanium dental implants were placed into augmented sites. After 8 weeks of allowed time for osseointegration, the animals were sacrificed to harvest block specimens for bone-to-implant contact (BIC) and ridge width histomorphometric analysis. Results: Polyethylene glycol membranes had an exposure rate of 50% as compared to 12.5% for sites grafted with CM. Regenerative outcomes with respect to implant placement were least favorable for FDBX + PEG which had implants placed in 37.5% of augmented sites compared to 100% implant placement for all other groups. No statistically significant differences were noted between groups for ridge width measurements in implant and non-implant histologic sections (P > 0.05). Buccal BIC (%) values between treatment groups also failed to reach statistical significant difference (FDBX + PEG [60.2 ± 9.4]; AB + PEG [58.8 ± 8.5]; AB + CM [57.9 ± 12.8]; AB [61.0 ± 10.2]). Conclusion: When used in conjunction with FDBX, PEG had unpredictable bone formation and in most cases negatively impacted future implant placement. [ABSTRACT FROM AUTHOR]

Objectives The objective of this experiment was to test whether or not a synthetic bone substitute ( SBS) was more effective than a polyethylene glycol hydrogel as a carrier material for bone morphogenetic protein-2 ( BMP-2) when attempting to regenerate bone. Material and methods Two identical, box-type dehiscence defects (4 × 4 mm buccolingually and apicocoronally, and 8 mm mesiodistally) were surgically prepared on buccal sides of the left and right edentulous ridge in five beagle dogs. Following implant placement, the defects either received (i) no graft, (ii) SBS+hydrogel, (iii) SBS+ BMP-2 loaded hydrogel, and (iv) BMP-2-loaded SBS+hydrogel. The animals were euthanized at 8 weeks postsurgery. Radiographic and histomorphometric analyses were performed. Results The hydrogel alone was not able to stabilize the grafted bone particles at 8 weeks, and SBS+hydrogel group did not significantly differ from the control group in all volumetric measurements. On the other hand, extensively regenerated new bone was connected with most of the remaining SBS particles in the BMP-2 groups. The BMP-2 groups exhibited significantly greater new bone formation (10.65 mm3 and 1.47 mm2 in the SBS+ BMP-2-loaded hydrogel group; 14.17 mm3 and 0.93 mm2 in the BMP-2-loaded SBS+hydrogel) than non- BMP-2 groups (1.27 mm3 and 0.00 mm2 in the control group; 2.01 mm3 and 0.19 mm2 in the SBS+hydrogel group) in volumetric and histomorphometric analyses ( P < 0.001). However, there were no significant differences between both BMP-2 groups. Conclusion BMP-2 could yield enhanced bone regeneration in the critical-size peri-implant defects regardless of whether SBS or hydrogel is used for preloading, although the outcomes seem to be more reproducible with BMP-2 preloaded on SBS. [ABSTRACT FROM AUTHOR]

Objective Biphasic calcium phosphates ( BCPs), mixture of hydroxyapatite ( HA) and β-tricalcium phosphate (β- TCP) are synthetic bone substitutes, which are increasingly used in adjunctive implant and periodontal surgery. The aim of this study was to evaluate the rate and amount of bone regeneration in defects filled with three different BCPs in relation to deproteinized bovine bone mineral ( DBBM). Method Ten New Zealand rabbits were used in the experiment. Four defects of 6 mm in diameter were prepared in each rabbit, and they were filled with different biomaterials: BCP with HA/β- TCP ratio of 60/40 ( BCPG1), ratio of 10/90 ( BCPG2), a BCP with polylactide incorporated (moldable BCP) and DBBM. Group A ( n = 5) rabbits were sacrificed after 3 months, and group B ( n = 5) were sacrificed 6 months after surgery. Histological and histomorphometric analyses were performed. Mean percentages of mineralized new bone (% MNB), bone marrow (% BM), residual grafting material (% RG) and soft tissue (% ST) were calculated for each bone substitute. Results Percentages of MNB in defects filled with the four bone substitutes were comparable after 3 months and 6 months. Amount of MNB regenerated for moldable BCP and DBBM after 6 months were significantly higher than after 3 months ( P < 0.05), whereas those for BCPG1 and BCPG2 did not show significant change. Percentage RG was significantly higher in moldable BCP compared with BCPG1 ( P < 0.05) after 3 months. Conclusion After 3 months, the granules-form synthetic materials performed better than DBBM in terms of bone regeneration. The grafting materials performed similarly after 6 months of healing. Addition of polylactide in moldable BCP may slow down osteogenesis in grafted defects. [ABSTRACT FROM AUTHOR]

Aim To test whether or not bone regeneration using deproteinized bovine bone mineral ( DBBM) is comparable to hydroxyapatite/silica oxide ( HA/SiO) and to test the effect of recombinant human bone morphogenetic protein-2 (rh BMP-2) as an adjunct to DBBM for localized bone regeneration. Materials and methods In each of the 10 rabbits, 4 titanium cylinders were placed on the external cortical plates of their calvaria. Four treatment modalities were randomly allocated: (i) empty, (ii) HA/SiO, (iii) DBBM, and (iv) DBBM plus rh BMP-2 ( DBBM/ BMP). The animals were sacrificed at week 8. Descriptive histology and histomorphometric assessment using a superimposed test grid of points and cycloids were performed. Results The mean number of points of the test grid coinciding with bone within the cylinder reached 124 ± 35 bone points for empty controls, 92 ± 40 bone points for DBBM, 98 ± 44 bone points for synthetic HA/SiO, and 146 ± 34 bone points DBBM/ BMP. The P-value for DBBM with and without BMP reached a borderline statistical significance of 0.051. However, the area of bone regeneration within the cylinders peaked for DBBM/ BMP and was statistically significantly higher compared with empty cylinders ( P < 0.05). The bone-to-bone substitute contact ranged between 32.9% ± 21.7 for DBBM, 39.6 ± 18.4% for HA/SiO, and 57.8% ± 10.2 for DBBM/ BMP. The differences between DBBM/ BMP and controls ( DBBM, HA/SiO) were statistically significant ( P < 0.05). Conclusions DBBM and HA/SiO rendered comparable amounts of bone regeneration. The addition of rh BMP-2 to DBBM resulted in more favorable outcomes with respect to the area of bone regeneration and to bone-to-implant contact, thereby indicating the potential of this growth factor to enhance bone regeneration within this animal model. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this controlled clinical study was to compare a polyethylene glycol membrane (PEG) used for bone regeneration of peri-implant defects to a collagen membrane with respect to implant survival rate, dimensions of buccal peri-implant bone and mucosa. Materials and methods: Thirty-seven patients who received single tooth implants with simultaneous guided bone regeneration (GBR) in the posterior maxilla or mandible were enrolled in the study. Intra-operative heights of bone defects were assessed prior to bone augmentation. The defects were augmented with xenogenic bone mineral and randomly covered either with a porcine collagen membrane (control) or with a PEG membrane (test). Five years after implant placement, clinical evaluation and cone beam computed tomography (CBCT) scans were performed. Remaining height of bone defect, horizontal bone thickness, level of mucosal margin, and mucosal thickness were assessed in CBCT images. The difference of height of bone defect at implant placement and at 5-year follow-up was calculated. The differences between the two groups were analyzed using two-sided t-test and Mann-Whitney U-test. Results: After 5 years, 32 patients could be included and exhibited an implant survival rate of 100% for both groups. The buccal vertical bone gain between implant placement and 5-year follow-up amounted at 4.3 ± 1.5 (SD) mm and 4.8 ± 2.6 (SD) mm for the control and the test group, respectively (P = 0.493). Neither the bone height nor the thickness reached statistical significant differences between the two groups. The distance between mucosal margin and implant shoulder resulted in 0.8 ± 0.7 (SD) mm in the control and 0.5 ± 0.8 (SD) mm in the test group (P = 0.198). The mucosal thickness reached 1.4 ± 0.5 (SD) mm in the control and 1.3 ± 0.3 (SD) mm in the test group (P = 0.715). There were no significant correlations between height of bone defect at baseline and at follow-up examination and between different 5-year parameters. Conclusion: A polyethylene glycol membrane used for bone regeneration of peri-implant defects performed as successfully as a collagen membrane with respect to implant survival rate and dimensions of the buccal peri-implant bone and mucosa after 5 years. [ABSTRACT FROM AUTHOR]

Objective To determine the early temporal-wide genome transcription regulation by the surface topography at the bone-implant interface of implants bearing microroughened or superimposed nanosurface topology. Materials and methods Four commercially pure titanium implants (2.2 × 5.0 mm) with either a moderately roughened surface ( Ti Oblast) or super-imposed nanoscale topography ( Osseospeed) were placed ( n = 2/surface) in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole-genome microarray using the Affymetrix Human gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces. Results There were no significant differences when comparing the two implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix ( ECM), collagen fibril organization, and angiogenesis were upregulated at both surfaces (day7 vs. day3). Abundant upregulation of several differential markers of alternative activated macrophages was observed (e.g., MRC1, MSR1, MS4 A4 A, SLC38 A6, and CCL18). The biological processes involved with the inflammatory/immune response gene expression were concomitantly downregulated. Conclusions Gene regulation implicating collagen fibrillogenesis and ECM organization as well as the inflammatory/immune responses involving the alternative activated pathway are observed in implant adherent cells at early (3-7 days) after implantation. These gene expression events may indicate a pivotal role of collagen fibrillogenesis as well as immunomodulation in altering bone accrual and biomechanical physical properties of the implant-bone interface. [ABSTRACT FROM AUTHOR]

Objective i) To test whether or not pH modifications of a PEG hydrogel matrix influence degradation time and bone regeneration in acute and unprepared (chronic) defects; and ii) to test whether or not the addition of a PEG hydrogel to hydroxyapatite/tricalciumphosphate (HA/TCP) can further enhance bone regeneration compared to HA/TCP alone in acute defects. Materials and methods In 11 mini-pigs, three acute standardized defects and one chronic site were prepared in each hemi-mandible. The following treatment modalities were applied in acute defects: PEG hydrogel regular (PEG 8.7), PEG hydrogel pH-modified plus (PEG 9.0), PEG hydrogel pH-modified minus (PEG 8.4), PEG 8.7 mixed with HA/TCP granules (PEG-HA/TCP), HA/TCP granules (HA/TCP), and empty control (control). In chronic sites, PEG 8.7 and PEG 9.0 were applied. Subsequently primary wound closure was obtained and animals sacrificed at 10 ( n = 6) and 21 days ( n = 5). Descriptive histology and histomorphometric analyses were performed including measurements for newly formed bone, remaining hydrogel, and percent defect fill. Standard descriptive statistics were calculated, and regression analysis used to determine the difference between treatments, taking into account relevant factors and correction for multiple comparisons. Results In acute defects, the amount of newly formed bone increased statistically significantly over time for all treatments. The increase was higher for PEG 8.7 (35.9%) compared with PEG 8.4 and PEG 9.0 and was higher for PEG- HA/ TCP (24.7%) than for HA/ TCP (14.6%). The remaining hydrogel ranged between 7.6 ± 13.3% for PEG 8.4 and 17.7 ± 12.8% for PEG 8.7 at 10 days. At 21 days, no remaining hydrogel was found except for PEG- HA/ TCP (11.5 ± 10.4%). In chronic sites, at 10 days, the remaining hydrogel covered 29.5 ± 10.3% ( PEG 9.0) and 25.6 ± 21.8% ( PEG 8.7) of the area. At 21 days, the amount of hydrogel (29.7 ± 31.7% for PEG 9.0; 1.4 ± 2.5% for PEG 8.7) decreased, while the amount of bone increased to 14.0 ± 16.3% for PEG 9.0 and to 37.9 ± 15.7% for PEG 8.7. Conclusions The PEG hydrogel matrix with a mid-range pH (PEG 8.7) may serve as a matrix for localized bone regeneration with or without the addition of a bone substitute material. This was demonstrated by enhanced bone regeneration in acute and chronic defects compared with control hydrogels and HA/TCP alone. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the early cellular attachment and viability to modified polyethylene glycol ( PEG) hydrogels with the influence of arginine-glycine-aspartic acid ( RGD) in an in vitro model system. Material and methods Human gingival fibroblasts ( HGF-1) were cultured on 6 different modalities of PEG hydrogel in hydrophobic polystyrene wells. A total of 7500 cells/well (10000 cells/cm2) were dispersed over the PEG filled wells and incubated in triplicates for 24 h, 7 and 13 days. Cell numbers were calculated by means of a Nucleo Counter. Cell viability was determined by measuring lactate dehydrogenase ( LDH). For statistical analysis, nonparametric Kruska- Wallis test followed by Dunetts T3 test were used. Results All PEG modifications showed good biocompatibility, as demonstrated by low LDH values per cell at the earlier two time points. After 13 days, all PEG modifications showed significantly lower number of cells compared with the controls, and the MX60 configurations demonstrated significantly higher LDH/cell values compared with the other hydrogels. Conclusions Modifications of the physio-chemical properties of PEG hydrogels and the addition of RGD and spacers influenced the initial cellular response of cultured HGF-1 cells. With the exception of MX60 after 13 days, all PEG formulations performed similarly well. Early cellular response should be considered when developing PEG-based material for clinical purposes. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate if osseous regeneration can be accelerated by involvement of periosteal tissue. Bone defect regeneration could be accelerated by the involvement of periosteal tissue if osteogenic cell signalling is maintained within the defect. It was questioned if local cell-mediated BMP-2 gene delivery makes a cell occlusive membrane dispensable during bone critical size defect regeneration. Methods: PEG matrix (degradation time 10 days) and PEG membrane (degradation time 120 days) were used in the pig calvarial model. Cylindrical (1 × 1 cm) critical size defects (CSD) (9 per animal; 20 animals) were filled with: (i) particulated autologous bone, covered with PEG membrane (group 1); (ii) HA/TCP, covered with PEG membrane (group 2); (iii) HA/TCP, mixed with PEG matrix (group 3); and (iv) HA/TCP mixed with BMP-2-transfected osteoblasts and PEG matrix (group 4). BMP-2/4 gene transfer: liposomal in vitro transfection of BMP-2/V5-tag fusion-protein. Quantitative histomorphometry (toluidine blue staining) after 2, 4 and 12 weeks assessed bone formation. Semiquantitative immunohistochemistry estimated the expression of BMP-2, V5-tag, Runx-2 and Sox9. Results: PEG matrix embedded BMP-2 expressing cells presented higher bone formation (P < 0.05) than HA/TCP + PEG matrix defect filling or PEG membrane covering (HA/TCP filling) after 12 weeks. Highest expression of BMP-2, Runx-2 and lowest expression of fibrous tissue marker Sox9 was seen in the BMP-2 group. Conclusion: PEG matrix embedded BMP-2 expressing cells are capable to maintain osteogenic signalling and to accelerate osseous defect regeneration in absence of a cell occlusive membrane. [ABSTRACT FROM AUTHOR]

Purpose This study addressed the suitability of a polyethylene glycol ( PEG) matrix as scaffold for cell-mediated local BMP-2 gene transfer in a calvarial critical size defect ( CSD) model. Materials and methods PEG matrix (degradation time 10 days) and PEG membrane (degradation time 120 days) were used in the pig calvarial model. Cylindrical (1 × 1 cm) CSD (9 per animal; 20 animals) were filled with: (i) HA/ TCP, covered by PEG membrane (group 1); (ii) HA/ TCP, mixed with PEG matrix (group 2); and (iii) HA/ TCP mixed with BMP-2 transfected osteoblasts and PEG matrix (group 3). BMP-2/4 gene transfer: liposomal in vitro transfection of BMP-2/ V5-tag fusion-protein. Quantitative histomorphometry (toluidine blue staining) after 2, 4 and 12 weeks assessed bone formation. Semiquantitative immunohistochemistry estimated the expression of BMP-2 and V5-tag. Results Group 3 showed significantly higher new bone formation than groups 1, 2 at 4 ( P < 0.05) and 12 ( P < 0.02) weeks. BMP-2- V5-tag was detected for 4 weeks. BMP-2 expression in group 3 was higher compared to all other groups after 2 and 4 ( P < 0.02) weeks. Conclusions The PEG matrix serves as scaffold for cell-mediated BMP-2 gene delivery in guided bone regeneration facilitating cell survival and protein synthesis for at least 4 weeks. Local BMP-2 gene delivery by PEG matrix-embedded cells leads to increased bone formation during critical size defect regeneration. [ABSTRACT FROM AUTHOR]

Objectives To evaluate by histology the effect of loading on the regenerated bone at dehiscence type defects around implants when treated with a combined approach of bone grafting and guided bone regeneration ( GBR). Materials and methods In twelve Göttingen mini-pigs, the lower premolars and first molars were extracted and the alveolar process was reduced in width. After 3 months, two Straumann SLActive® (Straumann AG, Basel, Switzerland) implants were placed in each hemi-mandible. Twelve implants were placed into the reduced alveolar ridge (group P) with no further defect or treatment on the site, while on 36 implants, buccal dehiscence defects were created and treated as follows: Group T1: synthetic bone substitute (Straumann Bone Ceramic®, SBC, Straumann AG). Group T2: SBC with a polyethylene glycol membrane (Straumann MembraGel®, Straumann AG); Group N: the dehiscence remained untreated. Three months following implantation, long, custom-made, healing abutments were placed in one hemi-mandible only to ensure functional loading. After 2 months, histological analysis was performed. Results A trend for lower residual defect height and higher bone-to-implant contact was observed in the loaded sites compared with non-loaded sites in groups P, T1 and N. In group T2, the opposite effect was observed. In terms of bone formation, sites treated with SBC grafting and GBR (group T2) exhibited the largest surface area of regenerated bone followed by T1 and N. Significant resorption of the graft particles was noted in group T2 and the graft surface area occupied by SBC was significantly higher in group T1 compared with group T2 ( P < 0.05). Conclusions Loading may have a positive effect on bone-to-implant contact in implants inserted in pristine bone or inserted in dehiscence sites and treated by grafting/no grafting. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the synergistic effect of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) on the repair of bone defects around dental implants. Material and methods: Five groups of scaffold were fabricated by a freeze-drying method, including pure chitosan/collagen scaffold; scaffold loaded with adenoviruses expressing BMP-2, adenoviruses expressing VEGF, both adenoviruses expressing BMP-2 and VEGF, VEGF protein and adenovirus expressing BMP-2. In vitro studies examined whether bone marrow stromal cells were responsive to these scaffolds over time. Bone formation capacity, bone-to-implant contact, as well as removal torque values were investigated in vivo. Differences between the various groups were statistically analyzed using the one-way analysis of variance test. Results: The in vitro study revealed a burst and rapid release of VEGF with a sustained high-level expression of BMP-2 in scaffold combined with VEGF protein and adenoviruses expressing BMP-2. Histomorphometry demonstrated that scaffolds expressing BMP-2 enhanced more bone formation compared with other groups; VEGF alone is insufficient to promote bone formation. New bone formation in the bone defects around dental implants, bone-to-implant contact and mean peak removal torque showed statistically significant difference for the adenoviral vector encoding human bone morphogenetic protein 2 (Ad-BMP-2) and VEGF protein and adenovirus expressing BMP-2 groups. Furthermore, scaffold combined with VEGF protein and Ad-BMP-2 represented the best outcomes in this model. Conclusions: A combination of BMP-2 gene and VEGF protein could have a synergistic effect in promoting bone healing. To cite this article: Luo T, Zhang W, Shi B, Cheng X, Zhang Y. Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein delivery. Clin. Oral Impl. Res. 23, 2012 467-474. doi: 10.1111/j.1600-0501.2011.02164.x [ABSTRACT FROM AUTHOR]

Objectives: To test whether or not an experimental polyethylene glycol (PEG) membrane maintains the bone graft volume and contributes to the preservation of the ridge contour in comparison with a commercially available synthetic membrane. Materials and methods: In 18 dogs, all mandibular premolars and the first molars were extracted. Ten weeks later, acute standardized defects were prepared. The defects of four dogs were randomly assigned to three modalities: (1) PEG plus deproteinized bovine bone mineral (DBBM) (PEG), (2) a resorbable glycolide trimethylene carbonate membrane plus DBBM (PGA-TMC), and (3) DBBM alone (DBBM). These dogs were then sacrificed for the baseline measurements. The remaining defects of 14 dogs were randomly assigned to (1) PEG plus DBBM, (2) PGA-TMC plus DBBM, (3) DBBM, and (4) empty defect. The dogs were sacrificed at baseline ( n=4), 4 weeks ( n=7), or at 16 weeks ( n=7). Mixed model regressions and the non-parametric Brunner-Langer method were applied for statistical analysis. Results: At baseline, equal tissue augmentation was observed in all groups. At 4 and 16 weeks, the greatest augmented area fractions were calculated for PEG (103%; 107%, respectively), followed by PGA-TMC (98%; 91%), DBBM (85%; 78%), and empty (46%; 54%), being statistically significant different ( P<0.001) between PEG and empty at 4 and 16 weeks, and PEG and DBBM at 16 weeks. The overall decrease ( P≤0.01) in the amount of bone graft between baseline and 16 weeks was −14% (PEG), −22% (PGA-TMC), and −23% (DBBM). Conclusions: The study demonstrates that the combination of the PEG membrane with DBBM maintains the bone graft volume over time better than controls. The PEG membrane with DBBM was also the most effective method to preserve the ridge contour. To cite this article: Thoma DS, Dard MM, Hälg G-A, Ramel CF, Hämmerle CHF, Jung RE. Evaluation of a biodegradable synthetic hydrogel used as a guided bone regeneration membrane: an experimental study in dogs. Clin. Oral Impl. Res. 23, 2012; 160-168. doi: 10.1111/j.1600-0501.2011.02217.x [ABSTRACT FROM AUTHOR]

Objectives: To assess the influence of two barrier membranes and two bone graft substitutes mixed with autogenous bone (AB) on staged guided bone regeneration and osseointegration of titanium implants in dogs. Materials and methods: Four saddle-type defects each were prepared in the upper jaw of six fox hounds and randomly filled with a natural bone mineral (NBM)+AB and a biphasic calcium phosphate (SBC)+AB and allocated to either an in situ gelling polyethylene glycol (PEG) or a collagen membrane (CM). At 8 weeks, modSLA titanium implants were inserted and left to heal in a submerged position. At 8+2 weeks, dissected blocks were processed for histomorphometrical analysis (e.g., treated area [TA], bone-to-implant contact [BIC]). Results: The mean TA values (mm2) and BIC values (%) tended to be higher in the PEG groups(TA: NBM+AB [10.4 ± 2.5]; SBC+AB [10.4 ± 5.8]/BIC: NBM+AB [86.4 ± 20.1]; SBC+AB [80.1 ± 21.5]) when compared with the corresponding CM groups (TA: NBM+AB [9.7 ± 4.8]; SBC+AB [7.8 ± 4.3]/BIC: NBM+AB [71.3 ± 20.8]; SBC+AB [72.4 ± 20.3]). A significant difference was observed for the mean TA values in the SBC+AB groups. Conclusion: It was concluded that all augmentation procedures investigated supported bone regeneration and staged osseointegration of modSLA titanium implants. However, the application of PEG may be associated with increased TA values. To cite this article: Schwarz F, Mihatovic I, Golubovic V, Hegewald A, Becker J. Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs: part 1. Augmentation using bone graft substitutes and autogenous bone. Clin. Oral Impl. Res. 23, 2012; 83-89. doi: 10.1111/j.1600-0501.2011.02187.x [ABSTRACT FROM AUTHOR]

Objectives: (i) To evaluate biodegradation, hard and soft tissue integration using various polyethylene glycol (PEG) hydrogels; (ii) to evaluate the influence of arginine-glycine-aspartic acid (RGD) on two types of PEG hydrogels. Material and methods: In seven rabbits, six treatment modalities were randomly applied subperiosteally on the skull: (1) a dense network PEG hydrogel (PEG1), (2) PEG1 modified with RGD (PEG1-RGD), (3) a looser network PEG hydrogel (PEG2), (4) PEG2 modified with RGD (PEG2-RGD), (5) a collagen membrane, and (6) a polylactide/polyglycolide/trimethylene carbonate membrane. The animals were sacrificed at 14 days. Histomorphometric analyses were performed on undecalcified Epon sections using a standardized region of interest. For statistical analysis, paired t-test and signed rank test were applied. Results: PEG1 and PEG1-RGD remained intact and maintained the shape. PEG2 and PEG2-RGD completely degraded and were replaced by connective tissue and bone. The largest amount of mineralized tissue was found for PEG2-RGD (21.4%), followed by PEG 2 (9.5%). The highest percentage of residual hydrogel/membrane was observed for PEG1-RGD (55.6%), followed by PEG1 (26.7%). Conclusions: Modifications of the physico-chemical properties of PEG hydrogels and the addition of RGD influenced soft and hard tissue integration and biodegradation. PEG1 showed an increased degradation time and maintained the shape. The soft tissue integration was enhanced by adding an RGD sequence. A high turn-over rate and extensive bone regeneration was observed using PEG2. The addition of RGD further improved bone formation and soft tissue integration. To cite this article: Thoma DS, Subramani K, Weber FE, Luder HU, Hämmerle CHF, Jung RE. Biodegradation, soft and hard tissue integration of various polyethylene glycol hydrogels: a histomorphometric study in rabbits. Clin. Oral Impl. Res. 22, 2011; 1247-1254. doi: 10.1111/j.1600-0501.2010.02075.x [ABSTRACT FROM AUTHOR]

The aim of the present study was to test whether the delivery of enamel matrix derivate (EMD) via synthetic polyethylene glycol (PEG)-based hydrogels with and without RGD sequences enhances bone formation in vivo. In each of 10 rabbits, four titanium cylinders were placed on the external cortical bones of their calvaria. The following four treatment modalities were randomly allocated: One of the four cylinders was left empty (control), the other three were filled with a combination of PEG matrix with hydroxyapatite/tricalciumphosphate (HA/TCP) granules and EMD in a concentration of 100 μg/ml (test 1) or 500 μg/ml (test 2) or 500 μg/ml and RGD peptide (test 3). After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis, the Kruskal-Wallis test was applied ( P<0.05). The histomorphometric analysis revealed a statistically larger area fraction of newly formed bone in the EMD 500/RGD group (54.8±14.5%) compared with the control group (28.7±10.3%) and the EMD 500 group (31.2±14.1%) and non-significantly higher area fraction compared with the EMD 100 group (38.2±10.4%). The percentage of mineralized bone showed no statistically significant differences among the four groups. The mean percentage of mineralized bone was 13.6±3.3% in the control group, 14.2±5.8% in the EMD 100 group, 11.69±5.9% in the EMD 500 group and 15.66±5.2% in the EMD 500/RGD group. No statistically significant difference regarding the bone-to-graft contact between the EMD 100 group (23±15.7%), the EMD 500 group (22.2±14.6%) and the EMD 500/RGD group (21.6±8.8%) was observed. The combination of a PEG matrix containing EMD with HA/TCP granules had no effect on the formation of mineralized bone tissue in rabbit calvaria. The addition of RGD peptide to the PEG/EMD 500 combination increased the area fraction of newly formed bone compared with the other treatment groups. Further studies are indicated to study a possible synergistic effect of EMD and RGD. Schneider D, Weber FE, Hämmerle CHF, Feloutzis A, Jung RE. Bone regeneration using a synthetic matrix containing enamel matrix derivate Clin. Oral Impl. Res, 2011; 214-222. doi: 10.1111/j.1600-0501.2010.01985.x [ABSTRACT FROM AUTHOR]

Collagenous and noncollagenous membranes have been investigated in many animal systems but their effects in the macaque model are unknown. To determine subcutaneous cellular reactions and degradation characteristics following implantation of collagenous and noncollagenous membranes in a macaque model. Six adult male Macaca fascicularis, aged above 7 years, were used. Six commercially available collagenous (Bio-Gide [BG], Tissue Fleece [TFL] TissueFoil E forte [TFO], Lycoll [LC], Surgicoll [SG] and Tutodent [TU]) and two noncollagenous (Tabotamp [TA] and Gelita-Tampon [GT]) membranes (size 2 × 2 cm each) were implanted in unconnected subcutaneous pouches in the monkey's back and wounds were allowed to heal by primary intention. The total sample size for each membrane was six. Two monkeys were sacrificed for each experimental period of 4, 14 and 28 days. Explanted specimens were prepared for histologic and histomorphometric analysis. Digitized images of implant sites were systematically sampled using an Image Analyzer with a grid containing 35 intersection points. Four parameters were quantified: membrane degradation, foreign body reaction, tissue organization and vascularization. Biodegradation rate and vascularization scored higher in collagenous than in noncollagenous membranes. Except for TFL and TU, the remaining six membranes showed a moderately intense foreign body reaction at week 2. Tissue organization was initiated early in four out of six collagenous (TFL>LC>SG>TFO>BG>TU) compared with one of two noncollagenous (TA>GT) membranes. The results suggest that differences in membrane structure and composition underlie their different cellular reactions and degradation characteristics. Siar CH, Toh CG, Romanos G, Ng KH. Subcutaneous reactions and degradation characteristics of collagenous and noncollagenous membranes in a macaque model. Clin. Oral Impl. Res. , 2011; 113-120. doi: 10.1111/j.1600-0501.2010.01970.x [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance and safety of Inion GTR™ Biodegradable Membrane System and Geistlich resorbable bilayer Bio-Gide® membrane in human bone regeneration. Material and methods: In a multicenter, split blind, comparative, randomized, prospective, pilot study 15 patients have been randomized at surgery whether to be treated either with Inion GTR™ Biodegradable Membrane System on one and Geistlich resorbable bilayer Bio-Gide® membrane on the other side or vice versa after surgical removal of both fully impacted wisdom teeth. During the follow-up visits at week 1, 2 and 6 and at months 3 and 6 the general state, the wound, eventual adverse events and the medication of the patients were assessed. Computed Tomography (CT) scans were performed immediately and 3 months after the surgery, before biopsy collection. Semi-quantitative histological evaluation and histomorphometric analyses were performed according to the ISO 10993-6 standard. New bone formation and membrane integration were evaluated by CT scan measurements. Tissue healing was evaluated clinically and by photographs between the time on teeth extraction and during follow ups. Results: Five patients were smokers, none drank alcohol. Mild adverse events like wound infection, haematoma or late swelling of the gums occurred in three patients. The trephine bur harvest of bone biopsies under local anaesthesia was uneventful. Whereas specimens from the sites treated with the Inion membrane yielded 17.0% (SD 24%), the Bio-Gide membrane sites yielded 13.5% (SD 15%) of bone tissue density. In sites treated with the Inion membrane, 9.5% of old bone density and 7.5% of newly formed bone could be found, whereas the Bio-Gide® membrane sites showed 3.8% of old bone density and 9.8% of newly formed bone. There were no statistically significant differences between the two groups with respect to the two variables. The osteoid rim was more extended with the Bio-Gide® (6.6 mm) than with the Inion membrane (5.1 mm) but the difference between the two treatments did not reach statistical significance. Highly significant reductions in the area of the defect with both membranes were detected with significant increases in CT density at the immediate inferio–buccal adjacent bone and in the surgical defect area with both membranes. However, there was neither significant change in CT density in the immediate inferior–lingual adjacent bone of the two membranes, nor significant difference between the membranes on any of the four measurements (area of defect: P=0.1354; CT density immediate inferio–buccal adjacent bone: P=0.7615; CT density surgical defect area: P=0.1876; CT density immediate inferio–lingual adjacent bone: P=0.4212). Conclusion: The overall clinical outcome was satisfying and the majority of the patients showed an uneventful healing phase. Both membranes presented similar capacities regarding their barrier function and were associated with analogous bone regeneration. No statistically valid evidence about the superiority of one particular membrane was obtained. For the patient the only difference is that one product is animal derived and the other synthetic. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate the pattern of biodegradation of different polyethylene glycol (PEG) hydrogel/RGD-peptide modifications in rats. Material and methods: Two different hydrogels were employed: (i) a combination of four-arm PEG-thiol, Mn=2.3 kDa, and eight-arm PEG-acrylate, Mn=2.3 kDa (PEG1); and (ii) a combination of four-arm PEG-thiol, Mn=2.3 kDa, and four-arm PEG-acrylate, Mn=15 kDa (PEG2). Both PEG1 and PEG2 were either used alone or combined with a nine amino acid cys-RGD peptide (RGD). A non-cross-linked porcine type I and III collagen membrane [BioGide® (BG)] served as control. Specimens were randomly allocated in unconnected subcutaneous pouches separated surgically on the back of 60 wistar rats, which were divided into six groups (1, 2, 4, 8, 16, and 24 weeks). Specimens were prepared for histological (tissue integration, foreign body reactions, biodegradation) and immunohistochemical (angiogenesis) analysis. Results: All materials investigated revealed unimpeded and comparable tissue integration without any signs of foreign body reactions. While BG exhibited transmembraneous blood vessel formation at 1 week, all PEG specimens were just surrounded by a well-vascularized connective tissue. The hydrolytic disruption of PEG1 and PEG1/RGD specimens was associated with an ingrowth of blood vessels at 4 weeks. Biodegradation times were highest for PEG1 (24 weeks)>PEG1/RGD (16 weeks)>BG (4 weeks)>PEG2=PEG2/RGD (2 weeks). Conclusion: Within the limits of the present study, it was concluded that (i) all materials investigated revealed a high biocompatibility and tissue integration, and (ii) hydrogel biodegradation was dependent on PEG composition. [ABSTRACT FROM AUTHOR]

Purpose: The aim was (1) to evaluate the soft-tissue reaction of a synthetic polyethylene glycol (PEG) hydrogel used as a barrier membrane for guided bone regeneration (GBR) compared with a collagen membrane and (2) to test whether or not the application of this in situ formed membrane will result in a similar amount of bone regeneration as the use of a collagen membrane. Material and methods: Tooth extraction and preparation of osseous defects were performed in the mandibles of 11 beagle dogs. After 3 months, 44 cylindrical implants were placed within healed dehiscence-type bone defects resulting in approximately 6 mm exposed implant surface. The following four treatment modalities were randomly allocated: PEG+autogenous bone chips, PEG+hydroxyapatite (HA)/tricalcium phosphate (TCP) granules, bioresorbable collagen membrane+autogenous bone chips and autogenous bone chips without a membrane. After 2 and 6 months, six and five dogs were sacrificed, respectively. A semi-quantitative evaluation of the local tolerance and a histomorphometric analysis were performed. For statistical analysis, repeated measures analysis of variance (ANOVA) and subsequent pairwise Student's t-test were applied ( P<0.05). Results: No local adverse effects in association with the PEG compared with the collagen membrane was observed clinically and histologically at any time-point. Healing was uneventful and all implants were histologically integrated. Four out of 22 PEG membrane sites revealed a soft-tissue dehiscence after 1–2 weeks that subsequently healed uneventful. Histomorphometric measurement of the vertical bone gain showed after 2 months values between 31% and 45% and after 6 months between 31% and 38%. Bone-to-implant contact (BIC) within the former defect area was similarly high in all groups ranging from 71% to 82% after 2 months and 49% to 91% after 6 months. However, with regard to all evaluated parameters, the PEG and the collagen membranes did not show any statistically significant difference compared with sites treated with autogenous bone without a membrane. Conclusion: The in situ forming synthetic membrane made of PEG was safely used in the present study, revealing no biologically significant abnormal soft-tissue reaction and demonstrated similar amounts of newly formed bone for defects treated with the PEG membrane compared with defects treated with a standard collagen membrane. [ABSTRACT FROM AUTHOR]

Objectives: The use of barrier membranes in guided bone regeneration (GBR) procedures for the treatment of alveolar bone defects is common practice. The objective of this study was to test whether a synthetic bioresorbable polyethylene glycol (PEG) hydrogel membrane could result in a similar amount of vertical bone fill as a standard collagen membrane, both combined with a membrane supporting material. Material and methods: The study enrolled 37 patients requiring implant treatment with an expected osseous defect in the posterior maxilla or mandible. After raising a mucoperiosteal flap, the implant sites were prepared and dental implants placed. The defect height was then measured and defects <3 mm were excluded from the study. Defects were grafted with bovine bone mineral and randomly covered with either a collagen membrane (control group, 18 patients) or a PEG hydrogel membrane (test group, 19 patients), which is applied as a liquid. After a healing period of 6 months, surgical re-entry was performed and the change in vertical bone height from baseline evaluated. Results: Well-vascularized hard tissue was apparent at all sites and the regenerated bone was similar to the surrounding native bone. Mean vertical defect fill after 6 months was 5.63±1.84 mm at test sites and 4.25±1.16 mm at control sites, and the mean defect fills were 94.9% and 96.4% at test and control sites, respectively. More soft tissue complications were observed with the PEG membrane (e.g., delayed or incomplete wound healing) but all sites recovered uneventfully. Conclusions: The new PEG hydrogel membrane was as successful as a standard collagen membrane in the treatment of bony dehiscence defects around dental implants with simplified clinical handling. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test whether a synthetic, biodegradable membrane made of polyethylene glycol (PEG) can prevent soft-tissue ingrowth into alveolar defects. Material and methods: In each of 16 minipigs, three mandibular premolars were bilaterally extracted. Three months later, acute standardized defects (diameter 8 mm, depth 8 mm) were prepared. Four treatment modalities were randomly allocated to the defects: (1) PEG membrane plus collagen sponge, (2) polylactide (PLA) membrane plus collagen sponge, (3) collagen sponge alone, and (4) empty defect. Animals were sacrificed at 10 days ( n=5), 21 days ( n=5), or 2 months ( n=6) after treatment. Qualitative and quantitative histological evaluations of soft-tissue ingrowth and bone regeneration were performed on nondecalcified ground sections. For statistical analysis, the Mann–Whitney–Wilcoxon test, the Kruskal–Wallis, and the paired t-test were applied. P-values were adjusted using the Dunnett–Hsu adjustment. Results: At 10 days, the PEG membrane group showed the least soft-tissue ingrowth (mean value −0.75 mm; range −1.35 to −0.10), followed by the PLA membrane group −0.18 mm (−0.80 to 0.44), the collagen group 0.04 mm (−0.65 to 0.73), and the empty defects 0.60 mm (−0.08 to 1.29). Statistically significant differences were observed between the PEG membrane group and the empty defects ( P<0.05). At 21 days, the highest percentage of newly formed bone was found in the PEG membrane group (mean 28.4%; range 21.6–35.2) compared with 23.7% (16.9–30.5; PLA membrane), 15.2% (8.2–22.2; collagen group), and 21.6% (14.5–28.8; empty defects). Statistically significant differences were only found between the PEG membrane group and the collagen group ( P<0.05). At 2 months, the tested parameters revealed no statistically significant differences between the groups. Conclusion: The experimental PEG membrane applied in the present study successfully prevented collapse of the covering soft tissues to a degree similar to the PLA membrane. The combination of a collagen sponge and the PEG membrane showed the least soft-tissue ingrowth at 10 days and promoted more bone formation at 21 days. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the efficacy of a new biphasic hydroxyapatite/tricalcium phosphate (HA/TCP) bone substitute in combination with particulate autogenous bone in sinus floor augmentation procedures. Material and methods: A simultaneous or a two-stage sinus augmentation and implant placement were conducted in 28 patients. A mixture of HA/TCP and autogenous bone chips in a 1 : 1 ratio was used as the grafting biomaterial. Cylindrical specimen bone retrieval was performed in all patients except one. Specimens were harvested either at 6 ( n=14) or 9 ( n=13) months post-augmentation. For histologic and histomorphometric evaluations, the non-decalcified tissue processing (Donath's technique) was performed. Results: Newly formed bone around the grafted particles was found in all samples. The encircling, highly cellular bone followed the outline of the grafted particles in direct contact. Both woven and lamellar types of bone were observed. Morphometrically, the total mean bone area fraction of all sections was 34.8±10.3%, increasing from 28.6±7.8% at 6 months to 41.6±8.3% at 9 months ( P<0.001). Mean particle area fraction average was 25.5±11.6% and 23.5±9.3% at 6 and 9 months, respectively, with a total mean of 24.5±10.4%. The increase in bone area fraction was not significantly correlated to the decrease of the grafted particles area fraction. Conclusions: The biphasic HA/TCP showed biocompatible and osteoconductive properties. This alloplast as a composite with autogenous bone chips promotes newly formed bone, which increases in its fraction along an extended healing period. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to test whether or not a synthetic matrix consisting of a polyethylene glycol (PEG) hydrogel containing recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with grafting materials enhances bone regeneration compared with grafting alone or empty control sites. Material and methods: In each of 10 rabbits, four titanium cylinders were screwed in perforated slits made in the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: (1) empty control, (2) a combination of a PEG matrix and hydroxyapatite/tricalciumphosphate (HA/TCP) granules and a combination of a PEG matrix containing either 10 μg/ml (3) or 30 μg/ml (4) of BMP-2 and HA/TCP granules. After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis repeated measures ANOVA and subsequent pairwise Student's t-test were applied ( P<0.01). Results: Histomorphometric analysis showed an average area fraction of newly formed bone of 13.96±5.98% for the empty control, 15.16±7.95% for the PEG and HA/TCP group, 26.32±8.56% for the group containing 10 μg rhBMP-2/ml, and 30.15±7.63% for the group containing 30 μg rhBMP-2/ml. Statistical analysis revealed significantly more newly formed bone in the two rhBMP-2 groups compared with the PEG and HA/TCP group and with the empty control. Regarding the surface fraction of the HA/TCP graft particles covered with newly formed bone the addition of rhBMP-2 revealed a more than two-fold increase compared with cylinders containing HA/TCP granules without rhBMP-2. This difference reached statistical significance. Conclusions: It is concluded that rhBMP-2 significantly enhances bone regeneration in rabbits when delivered by a synthetic matrix containing HA/TCP. This synthetic PEG matrix containing HA/TCP granules apparently fulfills a number of criteria required for an ideal carrier system for rhBMP-2. [ABSTRACT FROM AUTHOR]

The aim of the present study was to test whether or not the application of an in situ formed synthetic hydrogel made of polyethylene glycol (PEG) used as a biodegradable membrane for guided bone regeneration will result in the same amount of bone regeneration as with the use of an expanded polytetrafluoro-ethylene (ePTFE) membrane. In eight New Zealand White rabbits, four evenly distributed 6 mm diameter defects were drilled into the calvarial bone. Three treatment modalities were evenly distributed among the 32 defects: hydroxyapatite (HA)/tricalciumphosphate (TCP) granules covered at the outer and inner surface with a PEG membrane (test), HA/TCP granules covered at the outer and inner surface with an ePTFE membrane (positive control) and HA/TCP granules alone without membranes (negative control). After 4 weeks, the animals were sacrificed and the calvarial bones were removed. The area fraction of newly formed bone was determined by histomorphometrical analysis of the vertical sections from the middle of the defect and by micro-computed tomography of the entire defect. Multiple regression analysis (SAS® GLM) was used to model the amount of new bone formation. The quantitative histomorphometric analysis clearly revealed higher values of newly formed bone for the two membrane groups compared with the negative control group. The average area fractions of newly formed bone measured within the former defect amounted to 20.3±9.5% for the PEG membrane, 18.9±9.9% for the ePTFE membrane, and 7.3±5.3% for the sites with no membrane. The micro-computed tomography also showed higher values of new bone formation for the PEG and for the ePTFE groups compared with the negative control group. The GLM revealed a highly significant effect of the treatment on the amount of bone formation ( P=0.0048). The values for the negative control group were significantly lower than the ones found in the PEG membrane group ( P=0.0017), whereas the ePTFE membrane group showed no significant difference from the PEG membrane group. It is concluded that the PEG membrane can be used successfully as a biodegradable barrier membrane in the treatment of non-critical-size defects in the rabbit skull, and leads to similar amounts of bone regeneration as an ePTFE membrane. [ABSTRACT FROM AUTHOR]