Accuracy of cone beam computed tomography in assessing peri-implant bone defect regeneration: a histologically controlled study in dogs

Objective: To assess the accuracy of cone‐beam computed tomography (CBCT) in terms of buccal bone‐wall configuration and peri‐implant bone defect regeneration after guided bone regeneration (GBR). Material and methods: Titanium implants were inserted into standardized box‐shaped defects in the mandible of 12 foxhounds. Defects of one side were augmented following the principle of GBR, while the other side was left untreated. Radiological evaluation was performed using CBCT and compared with histomorphometrical measurements of the respective site serving as a validation method. Results: Non‐augmented control sites providing a horizontal bone width (BW) of<0.5 mm revealed a significantly lower accuracy between the radiological and the histological evaluation of the buccal defect depth (1.93 ± 1.59 mm) compared with the group providing a BW of >0.5 mm (0.7 ± 0.7 mm) (P<0.05, Mann–Whitney U‐test). In GBR‐treated defects, the subgroup <0.5 mm (1.49 ± 1.29 mm) revealed a significantly higher difference between CBCT and histology compared with >0.5 mm (0.82 ± 1.07) (P>0.05, Mann–Whitney U‐test). However, a radiological discrimination between original bone, integrated and non‐integrated bone substitute material was not reliable. Additionally, it was found that a minimum buccal BW of 0.5 mm was necessary for the detection of bone in radiology. Conclusion: The evaluation of peri‐implant bone defect regeneration by means of CBCT is not accurate for sites providing a BW of <0.5 mm. Moreover, a safe assessment of the success of the GBR technique is not possible after the application of a radiopaque bone substitute material. To cite this article:
Fienitz T, Schwarz F, Ritter L, Dreiseidler T, Becker J, Rothamel D. Accuracy of cone beam computed tomography in assessing peri‐implant bone defect regeneration: a histologically controlled study in dogs.
Clin. Oral Impl. Res. 23 , 2012; 882–887.
doi: 10.1111/j.1600‐0501.2011.02232.x     

The use of human hypertrophic chondrocytes-derived extracellular matrix for the treatment of critical-size calvarial defects

Objectives: To evaluate the effect of immortalized hypertrophic chondrocytes extracellular matrix (HCM) with or without the use of guided bone regeneration (GBR) on the healing of critical‐size calvarial defects. Material and methods: In 42 rats, 5 mm critical‐size calvarial defects were surgically created. The animals were randomly allocated to six groups of seven rats each: Group A1: one defect was left untreated (control), while the contralateral defect was covered by a double non‐resorbable membrane (GBR). Group B1: one defect was filled with calcium phosphate cement (CP), while the contralateral defect was treated with GBR and CP. Group C1: one defect was filled with a mixture of CP and HCM, while the contralateral defect was treated with GBR and CP+HCM. The healing period for all three groups was 30 days. The remaining three groups were treated in a similar manner but the healing period was 60 days. Five animals from each group were evaluated by maceration and two animals were analysed histologically. Results: At 30 days, all the control‐treated defects did not present complete closure. When GBR was applied alone or combined with CP, 3/5 and 5/5 defects, respectively, presented complete closure. At 60 days, one defect from the control group presented complete closure. All the defects treated with GBR alone presented complete closure, whereas the combined use of GBR with CP or CP+HCM resulted in 4/5 and 3/5 defects with complete closure, respectively. The only treatment modality that did not present any specimen with defect closure at both 30 and 60 days was the combination of CP+HCM. The histological analysis indicated that when GBR was not used alone, the healing consisted of an amorphous acellular structure and loose granulation tissue, which, even though clinically resembled hard tissue, did not demonstrate the histological characteristics of bone. Conclusion: The predictability of bone formation in critical‐size defects depends mainly on the presence or absence of barrier membranes. The combined use of GBR with calcium phosphate alone or in combination with immortalized human HCM did not enhance the potential for osseous healing provided by the GBR procedure. To cite this article:
Donos N, Graziani F, Mardas N, Kostopoulos L. The use of human hypertrophic chondrocytes‐derived extracellular matrix for the treatment of critical‐size calvarial defects.
Clin. Oral Impl. Res. xx , 2011; 000–000.
doi: 10.1111/j.1600‐0501.2010.02120.x     

Immunohistochemical characterization of guided bone regeneration at a dehiscence-type defect using different barrier membranes: an experimental study in dogs

Objectives: The aim of the present study was to evaluate immunohistochemically the pattern of guided bone regeneration (GBR) using different types of barrier membranes. Material and methods: Standardized buccal dehiscence defects were surgically created following implant bed preparation in 12 beagle dogs. Defects were randomly assigned to six different GBR procedures: a collagen‐coated bone grafting material (BOC) in combination with either a native, three cross‐linked, a titanium‐reinforced collagen membrane, or expanded polytetrafluorethylene (ePTFE), or BOC alone. After 1, 2, 4, 6, 9, and 12 weeks of submerged healing, dissected blocks were processed for immunohistochemical (osteocalcin – OC, transglutaminase II – angiogenesis) and histomorphometrical analysis [e.g., bone‐to‐implant contact (BIC), area of new bone fill (BF)]. Results: In general, angiogenesis, OC antigen reactivity, and new bone formation mainly arose from open bone marrow spaces at the bottom of the defect and invaded the dehiscence areas along the implant surface and BOC. At 4 weeks, membranes supporting an early transmembraneous angiogenesis also exhibited some localized peripheral areas of new bone formation. However, significantly increasing BIC and BF values over time were observed in all groups. Membrane exposure after 10–12 weeks was associated with a loss of the supporting alveolar bone in the ePTFE group. Conclusion: Within the limits of the present study, it was concluded that (i) angiogenesis plays a crucial role in GBR and (ii) all membranes investigated supported bone regeneration on an equivalent level.     

Clinical and radiographic comparison of implants in regenerated or native bone: 5-year results

Purpose: The aim of this study was to test whether or not implants associated with bone regeneration show the same survival and success rates as implants placed in native bone in patients requiring both forms of therapy. Material and methods: Thirty‐four patients (median age of 60.3 years, range 18–77.7 years) had been treated 5 years before the follow‐up examination. Machined screw‐type implants were inserted following one of two surgical procedures: (1) simultaneously with a guided bone regeneration (GBR) procedure, which involved grafting with xenogenic bone substitute material, autogenous bone or a mixture of the two and defect covering with a bio‐absorbable collagen membrane (test) and (2) standard implantation procedure without bone regeneration (control). For data recording, one test and one control implant from each patient were assessed. Examination included measurements of plaque control record (PCR), probing pocket depth (PPD), bleeding on probing (BOP), width of keratinized mucosa (KM), frequency of situations with supra‐mucosal location of the crown margin, implant survival assessment and radiographic examination. Radiographs were digitized to assess the marginal bone level (MBL). Differences between groups were tested using the one‐sample t‐test. The estimation of survival rate was based on Kaplan–Meier analysis. Results: The follow‐up period of the 34 GBR and 34 control implants ranged from 49 to 70 months (median time 57 months). Cumulative survival rates reached 100% for the GBR group and 94.1% for the control group without statistical significance. No statistically significant differences for clinical and radiographic parameters were found between the two groups regarding PCR, BOP, PPD, KM and MBL. Conclusion: The present study showed that, clinically, implants placed with concomitant bone regeneration did not performed differently from implants placed into native bone with respect to implant survival, marginal bone height and peri‐implant soft tissue parameters.     

Biological properties of an anti‐bacterial membrane for guided bone regeneration: an experimental study in rats

Objective: The biosafety and efficacy of silver–hydroxyapatite–titania/polyamide nanocomposite (nAg–HA–TiO₂/PA) membrane as a guided bone regeneration (GBR) barrier were investigated based on a rat subcutaneous and critical‐size calvarial defect model. Material and methods: Thirty‐six Sprague–Dawley albino rats were divided into nAg–HA–TiO₂/PA membrane test, expanded polytetrafluoroethylene (e‐PTFE) membrane control and blank control. Inflammatory response and bone regeneration in each group were evaluated using morphological, serological, radiographic and histological techniques at 1, 4 and 8 weeks, respectively, after implantation. Results: For subcutaneous implantation, slight degradation of nAg–HA–TiO₂/PA membranes was observed by scanning electron microscope at 4 and 8 weeks. Histopathologic examination demonstrated a thinner layer of granulation tissue in the vicinity of nAg–HA–TiO₂/PA membranes than that of e‐PTFE membranes. For cranial defect implantation, the serum alkaline phosphatase level was remarkably higher in nAg–HA–TiO₂/PA group than that in e‐PTFE group. Radiographic and histomorphometric analysis showed a fully closed cranial defect for both nAg–HA–TiO₂/PA and e‐PTFE groups at 8 weeks. No remarkable difference was found between the two groups regarding the integral optical density of neo‐bone at each time interval. Conclusion: nAg–HA–TiO₂/PA membranes demonstrated better biocompatibility and similar osteoinductive activity compared with e‐PTFE membranes. nAg–HA–TiO₂/PA composite membranes provided a good prospect for further research and development in anti‐bacterial GBR membrane. To cite this article:
Zhang JC, Xu Q, Huang C, Mo AC, Li JD, Zuo Y. Biological properties of an anti‐bacterial membrane for guided bone regeneration: an experimental study in rats.
Clin. Oral Impl. Res. 21 , 2010; 321–327.
doi: 10.1111/j.1600‐0501.2009.01838.x     

Guided Bone Regeneration: biological principle and therapeutic applications

The Guided Bone Regeneration (GBR) treatment concept advocates that regeneration of osseous defects is predictably attainable via the application of occlusive membranes, which mechanically exclude non‐osteogenic cell populations from the surrounding soft tissues, thereby allowing osteogenic cell populations originating from the parent bone to inhabit the osseous wound. The present review discusses the evolution of the GBR biological rationale and therapeutic concept over the last two decades. Further, an overview of the GBR research history is provided with specific focus on the evidence available on its effectiveness and predictability in promoting the regeneration of critical size cranio‐maxillo‐facial defects, the neo‐osteogenesis potential and the reconstruction of atrophic alveolar ridges before, or in conjunction with, the placement of dental implants. The authors conclude that future research should focus on (a) the investigation of the molecular mechanisms underlying the wound healing process following GBR application; (b) the identification of site and patient related factors which impact on the effectiveness and predictability of GBR therapy and (c) the evaluation of the pathophysiology of the GBR healing process in the presence of systemic conditions potentially affecting the skeletal system. To cite this article:
Retzepi M, Donos N. Guided Bone Regeneration: biological principle and therapeutic applications.
Clin. Oral Impl. Res. 21 , 2010; 567–576.
doi: 10.1111/j.1600‐0501.2010.01922.x     

Alveolar bone formation at dental implant dehiscence defects following guided bone regeneration and xenogeneic freeze‐dried demineralized bone matrix

The present study evaluated rate and extent of alveolar bone formation in dental implant dehiscence defects following guided bone regeneration(GBR) and implantation of xenogeneic freeze‐dried demineralized bone matrix (xDBM). A total of 16 titanium plasma‐sprayed (TPS) and 16 hydroxyapatite‐coated (HA) titanium cylinder implants were inserted in 4 mongrel dogs following extraction of the mandibular premolar teeth. Four implant sites per jaw quadrant (2 TPS and 2 HA implant sites) were prepared into extraction sockets in each dog. Buccal alveolar bone was removed to create 3 x 5 mm dehiscence defects. Two jaw quadrants in separate animals received GBR, GBR+xDBM, xDBM (control), or gingival flap surgery alone (GFS; control). Thus, four conditions were available for each implant type (TPS or HA): GBR, GBR+xDBM; xDBM and GFS. The animals received fluorescent bone labels to allow observations of rate and extent of bone formation. Animals were sacrificed at 12 weeks postsurgery and block sections were harvested for histologic analysis. There were no apparent histologic differences between TPS and HA implant defects. GBR and GBR+xDBM resulted in almost complete bone closure of the dental implant dehiscence defect. Rate of bone formation appeared higher following GBR alone. Extent of bone formation appeared somewhat greater following GBR+xDBM; however, delayed. xDBM alone did not adequately resolve the bony defect. In conclusion, GBR results in rapid, clinically relevant bone closure of dental implant dehiscence defects. Adjunctive implantation of xDBM does not appear to significantly improve the healing response in the model used.     

The effect of non-resorbable membrane on buccal bone healing at an immediate implant site: an experimental study in dogs

Objective: For successful implant treatment in the esthetic area, stable hard tissue and soft tissue are very important. At the buccal side without buccal bone defects, prophylactic guided bone regeneration (GBR) with bone substitute was frequently used for achieving thick buccal bone. The aim of this study was to evaluate the effect of GBR using a non‐resorbable membrane in an immediate implant site without bone defects. Material and methods: Immediate implants were placed into the mandibles of four mongrel dogs. In the experimental group (TM group), a non‐resorbable membrane was placed and fixed onto the buccal bone plate around the implant. In the control group, the implants were placed without membrane coverage. After 12 weeks, the dogs were sacrificed and histological specimens were prepared. The vertical distances from the smooth–rough surface interface (SRI) to the gingiva, the first‐bone contact, and the bone crest were measured on the buccal and lingual sides. The horizontal thicknesses of the gingiva and bone at 0, 1, 2, and 3 mm below the SRI were measured. Results: In the TM group, first‐bone contact on the buccal side was more coronally positioned approximately 0.8 mm than the control group (P=0.041). The buccal bone thickness of the TM group was well preserved and there was no difference between the buccal and lingual sides. Comparing the control group, implants of the TM group had 1 mm thicker buccal bone (P=0.0051 at bone 1 mm level, P=0.002 at bone 2 mm level). In the control group, buccal bone loss was observed and buccal bone was about 1 mm thinner than the lingual bone (P<0.05). Conclusions: GBR with a non‐resorbable membrane and no bone graft substitute could help to preserve buccal bone thickness on the immediate implant site without defects. To cite this article:
Park S‐Y, Kye S‐B, Yang S‐M, Shin S‐Y. The effect of non‐resorbable membrane on buccal bone healing at an immediate implant site: an experimental study in dogs.
Clin. Oral Impl. Res. 22 , 2011; 289–294.
doi: 10.1111/j.1600‐0501.2010.01995.x     

A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs

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.     

Alveolar bone formation at dental implant dehiscence defects following guided bone regeneration and xenogeneic freeze-dried demineralized bone matrix.

The present study evaluated rate and extent of alveolar bone formation in dental implant dehiscence defects following guided bone regeneration (GBR) and implantation of xenogeneic freeze-dried demineralized bone matrix (xDBM). A total of 16 titanium plasma-sprayed (TPS) and 16 hydroxyapatite-coated (HA) titanium cylinder implants were inserted in 4 mongrel dogs following extraction of the mandibular premolar teeth. Four implant sites per jaw quadrant (2 TPS and 2 HA implant sites) were prepared into extraction sockets in each dog. Buccal alveolar bone was removed to create 3 x 5 mm dehiscence defects. Two jaw quadrants in separate animals received GBR, GBR + xDBM, xDBM (control), or gingival flap surgery alone (GFS; control). Thus, four conditions were available for each implant type (TPS or HA): GBR, GBR + xDBM; xDBM and GFS. The animals received fluorescent bone labels to allow observations of rate and extent of bone formation. Animals were sacrificed at 12 weeks postsurgery and block sections were harvested for histologic analysis. There were no apparent histologic differences between TPS and HA implant defects. GBR and GBR + xDBM resulted in almost complete bone closure of the dental implant dehiscence defect. Rate of bone formation appeared higher following GBR alone. Extent of bone formation appeared somewhat greater following GBR + xDBM; however, delayed. xDBM alone did not adequately resolve the bony defect. In conclusion, GBR results in rapid, clinically relevant bone closure of dental implant dehiscence defects. Adjunctive implantation of xDBM does not appear to significantly improve the healing response in the model used.     

The effect of matrix bound parathyroid hormone on bone regeneration

Introduction: Autogenous bone is the most successful bone‐grafting material; however, multiple disadvantages continue to drive developments of improved methods for bone regeneration. Aim: The aim of the present study was to test the hypothesis that an arginine–glycine–aspartic acid (RGD) modified polyethylene glycol‐based matrix (PEG) containing covalently bound peptides of the parathyroid hormone (PTH_1?34) enhances bone regeneration to a degree similar to autogenous bone. Material and methods: Six American foxhounds received a total of 48 cylindrical titanium implants placed in the mandible between the first premolar and the second molar. Five, respectively, 7 months following tooth extraction, implants were placed into the center of surgically created defects. This resulted in a circumferential bone defect simulating an alveolar defect with a circular gap of 1.5 mm. Four treatment modalities were randomly allocated to the four defects per side: (1) PEG‐matrix containing 20 μg/ml of PTH_1?34, and 350 μg/ml cys‐RGD peptide, (2) PEG alone, (3) autogenous bone and (4) empty defects. Histomorphometric analysis was performed 4 and 12 weeks after implantation. The area fraction of newly formed bone was determined within the former defect and the degree of bone‐to‐implant contact (BIC) was evaluated both in the defect region and in the apical region of the implant. For statistical analysis ANOVA and subsequent pairwise Student's t‐test were applied. Results: Healing was uneventful and all implants were histologically integrated. Histomorphometric analysis after 4 weeks showed an average area fraction of newly formed bone of 41.7±1.8% for matrix‐PTH, 26.6±4.1% for PEG alone, 43.9±4.5% for autogenous bone, and 28.9±1.5% for empty defects. After 12 weeks, the respective values were 49.4±7.0% for matrix‐PTH, 39.3±5.7% for PEG alone, 50.5±3.4% for autogenous bone and 38.7±1.9% for empty defects. Statistical analysis after 4 and 12 weeks revealed significantly more newly formed bone in the PTH_1?34 group compared with PEG alone or empty defects, whereas no difference could be detected against autogenous bone. Regarding BIC no significant difference was observed between the four treatment groups neither at 4 nor at 12 weeks. Conclusion: It is concluded that an RGD‐modified PEG hydrogel containing PTH_1?34 is an effective matrix system to obtain bone regeneration.     

Treatment of ligature-induced peri-implantitis defects by regenerative procedures: a clinical study in dogs

We carried out a clinical evaluation of the hard tissue fill following treatment of ligature-induced peri-implantitis in dogs. Four dogs were used and their mandibular premolars (P2, P3 and P4) were removed. After 3 months of healing, two titanium implants were placed on each side of the mandible. After 3 months, the abutment connection was performed, and experimental peri-implantitis was induced by placement of cotton ligatures in a submarginal position. The ligatures and abutments were removed after one month, and the peri-implant bone defects were assigned randomly to one of the treatments: debridement (control), debridement plus guided bone regeneration (GBR), debridement plus mineralized bone graft (BG), and debridement plus guided bone regeneration associated with a mineralized bone graft (GBR + BG). Clinical measurements of the peri-implant bone defects before and 5 months after treatment revealed no statistically significant differences between the defects treated by GBR, BG and GBR + BG. These 3 treatment methods provided more hard tissue fill than debridement alone (p < 0.05). Thus, it can be concluded that GBR, BG or a combination of the two techniques can enhance the hard tissue fill in defects caused by peri-implantitis in dogs.     

Comparative analysis of collagen membranes for the treatment of implant dehiscence defects

Guided bone regeneration (GBR) evolved from the concept of guided tissue regeneration (GTR) and has been used for reconstructing sites with bone deficiencies associated with dental implants. For GBR, the use of absorbable collagen membranes has been increasing, but, at present, scientific information on the use of collagen membranes for GBR is limited. This study was aimed to clinically and histomorphometrically compare two collagen membranes, Bio-Gide(R) and BioMend ExtendTM, for the treatment of implant dehiscence defects in eight mongrel dogs. Implant dehiscence defects were surgically created in edentulous ridges, followed by the placement of three endosseous implants bilaterally in the mandible. Each implant dehiscence defect was randomly assigned to one of three treatment groups: (1) control (no membrane), (2) porcine dermis collagen barrier (Bio-Gide) or (3) bovine tendon collagen barrier (BioMend Extend). Dogs were sacrificed at 4 and 16 weeks (four dogs each) after treatment. Histomorphometric analysis included percentage linear bone fill (LF), new bone-to-implant contact (BIC) and area of new bone fill (BF). The results of the study revealed no significant differences among groups for any parameter at 4 weeks. However, at 16 weeks, more LF, BIC, and BF were noted in the membrane-treated groups than controls. BioMend Extend-treated defects demonstrated significantly greater BIC than control (P < 0.05) at this time point. BIC at 16 weeks was significantly greater than 4-week BIC (P < 0.05). Membrane exposure occurred in 9 out of 15 sites examined, resulting in significantly less LF and BIC than the sites without membrane exposure (P < 0.05). The results of this study indicate that: (1) GBR treatment with collagen membranes may significantly enhance bone regeneration, manifested at late stage (16 weeks) of healing; and (2) space maintenance and membrane coverage were the two most important factors affecting GBR using bioabsorbable collagen membranes.     

Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein delivery

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     

Effect of Doxycycline in Gel Form on Bone Regeneration: Histomorphometric and Tomographic Study in Rat Calvaria

Background: This study aims to investigate the effects of the local application of doxycycline in the form of natrosol‐based gel on bone regeneration by examining critical defects in rat calvaria. Methods: Twenty‐four rats were randomly divided into three groups with eight animals each, according to the treatment received: BC (untreated, filled with blood clot), NAT (natrosol gel alone), and DOX (10% doxycycline gel). Four animals from each group were euthanized at 4 and 8 weeks postoperatively. In tomographic analysis, mean density in the region of the defect was calculated as a percentage relative to the native bone density. In histomorphometric analysis, the newly formed bone area was calculated as a percentage of the total area. The values obtained underwent analysis of variance and Tukey testing (P <0.05). Results: The mean percentage of tomographic density in the region of the defect at the end of 8 weeks was higher for DOX (44.37%), and statistical differences in this period were observed between DOX and NAT (33.10%) and DOX and BC (32.43%). Regarding new bone formation, at the end of 8 weeks, DOX (61.11%) also had the highest mean bone formation, and statistical differences were observed between DOX and NAT (34.61%) and DOX and BC (23.11%). Conclusion: It was observed that 10% doxycycline gel had a good effect on bone regeneration regarding the filling of critical defects in rat calvaria.     

Evaluation of a biodegradable synthetic hydrogel used as a guided bone regeneration membrane: an experimental study in dogs

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     

Hard tissue volume stability of guided bone regeneration during the healing stage in the anterior maxilla: A clinical and radiographic study

Background

Guided bone regeneration (GBR) is currently the most widely used technique to reconstruct localized peri‐implant bone defects.

Objectives

To evaluate hard tissue volume stability during the healing stage of GBR with particulate bone graft and resorbable collagen membrane.

Materials and methods

Twenty‐eight patients who were missing a single maxillary incisor and required implant placement combined with GBR were randomly assigned to 2 groups: submerged (n = 14) and transmucosal (n = 14) healing groups. Cone‐beam computed tomography (CBCT) was performed before, immediately after and 6 months post‐surgery. The 3 sets of CBCT data were three‐dimensionally reconstructed and superimposed. Horizontal hard tissue alterations at different vertical levels were recorded. The relative position and distances from the boundary line of the bony defect envelope to the outlines of the augmented ridge were determined immediately post‐augmentation and 6 months after healing.

Results

Augmented ridge underwent horizontal volume reduction during the healing period. Vertical levels (P = .000) rather than healing strategies (submerged or transmucosal) (P = .182) had statistically significant impacts on the reduction width. The boundary line of the ridge defect envelope located within the bony profile immediately after surgery, but outside of the bony profile after 6 months.

Conclusions

GBR with resorbable membrane and particulate bovine bone would undergo horizontal volume reduction during the healing stage. New bone formation at the coronal site may only be predictable within the bony envelope.     

Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects

BACKGROUND: Alveolar ridge aberrations commonly require bone augmentation procedures for optimal placement of endosseous dental implants. The objective of this study was to evaluate local bone formation following implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier with or without provisions for guided bone regeneration (GBR) as potential treatment modalities for alveolar augmentation. METHODS: Surgically induced, large, mandibular alveolar ridge saddle-type defects (2 defects/jaw quadrant) in seven young adult Hound dogs were assigned to receive rhBMP-2/ACS, rhBMP-2/ACS combined with GBR (rhBMP-2/GBR), GBR, and surgery controls. The animals were euthanized at 12 weeks post-surgery when block sections of the defect sites were collected for histologic analysis. RESULTS: Clinical complications included swelling for sites receiving rhBMP-2 and wound failure with exposure of the barrier device for sites receiving GBR (4/6) or rhBMP-2/GBR (3/7). The radiographic evaluation showed substantial bone fill for sites receiving rhBMP-2/ACS, rhBMP-2/GBR, and GBR. In particular, sites receiving rhBMP-2/GBR presented with seroma-like radiolucencies. The surgery control exhibited moderate bone fill. To evaluate the biologic potential of the specific protocols, sites exhibiting wound failure were excluded from the histometric analysis. Sites receiving rhBMP-2/ACS or rhBMP-2/GBR exhibited bone fill averaging 101%. Bone fill averaged 92% and 60%, respectively, for sites receiving GBR and surgery controls. Bone density ranged from 50% to 57% for sites receiving rhBMP-2/ACS, GBR, or surgery controls. Bone density for sites receiving rhBMP-2/GBR averaged 34% largely due to seroma formation encompassing 13% to 97% of the sites. CONCLUSION: rhBMP-2/ACS appears to be an effective alternative to GBR in the reconstruction of advanced alveolar ridge defects. Combining rhBMP-2/ACS with GBR appears to be of limited value due to the potential for wound failure or persistent seromas.     

Effect of rhBMP-2 on guided bone regeneration in humans

Abstract: The aim of the present clinical study was to test whether or not the addition of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) to a xenogenic bone substitute mineral (Bio‐Oss^®) will improve guided bone regeneration therapy regarding bone volume, density and maturation. In 11 partially edentulous patients, 34 Brånemark implants were placed at two different sites in the same jaw (five maxillae, six mandibles) requiring lateral ridge augmentation. The bone defects were randomly assigned to test and control treatments: the test and the control defects were both augmented with the xenogenic bone substitute and a resorbable collagen membrane (Bio‐Gide^®). At the test sites, the xenogenic bone substitute mineral was coated with rhBMP‐2 in a lyophilization process. Following implant insertion (baseline), the peri‐implant bone defect height was measured from the implant shoulder to the first implant–bone contact. After an average healing period of 6 months (SD 0.17, range 5.7–6.2), the residual defects were again measured and trephine burs were used to take 22 bone biopsies from the augmented regions. The healing period was uneventful except for one implant site that showed a wound dehiscence, which spontaneously closed after 4 weeks. Later at reentry, all implants were stable. At baseline, the mean defect height was 7.0 mm (SD 2.67, range 3–12 mm) at test and 5.8 mm (SD 1.81, range 3–8 mm) at control sites. At reentry, the mean defect height decreased to 0.2 mm (SD 0.35, range 0–1 mm) at test sites (corresponding to 96% vertical defect fill) and to 0.4 mm (SD 0.66, range 0–2 mm) at the control site (vertical defect fill of 91%). Reduction in defect height from baseline to reentry for both test and control sites was statistically significant (Wilcoxon P<0.01). Histomorphometric analysis showed an average area density of 37% (SD 11.2, range 23–51%) newly formed bone at test sites and 30% (SD 8.9, range 18–43%) at control sites. The fraction of mineralized bone identified as mature lamellar bone amounted to 76% (SD 14.4, range 47.8–94%) at test compared to 56% (SD 18.3, range 31.6–91.4%) at control sites (paired t‐test P<0.05). At BMP‐treated sites 57% (SD 16.2, range 29–81%) and at control sites 30% (SD 22.6, range 0–66%) of the surface of the bone substitute particles were in direct contact with newly formed bone (paired t‐test P<0.05). It is concluded that the combination of the xenogenic bone substitute mineral with rhBMP‐2 can enhance the maturation process of bone regeneration and can increase the graft to bone contact in humans. rhBMP‐2 has the potential to predictably improve and accelerate guided bone regeneration therapy.