Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Part 2: augmentation using bone graft substitutes

Objectives: To assess the influence of two barrier membranes and two bone graft substitutes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Materials and methods: Saddle‐type defects were prepared in the lower jaws of 6 fox hounds and randomly filled with a natural bone mineral (NBM) and a biphasic calcium phosphate (SBC) 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, respectively, dissected blocks were processed for histomorphometrical analysis (e.g., mineralized tissue [MT], bone‐to‐implant contact [BIC]). Results: The mean MT values (mm²) and BIC values (%) tended to be higher in the PEG groups (MT: NBM [3.4±1.7]; SBC [4.2±2]/BIC: NBM [67.7±16.9]; SBC [66.9±17.8]) when compared with the corresponding CM groups (MT: NBM [2.5±0.8]; SBC [2.3±1.6]/BIC: NBM [54.1±22.6]; SBC [61±8.7]). These differences, however, did not reach statistical significance. Conclusion: It was concluded that all augmentation procedures investigated supported bone regeneration and staged osseointegration of modSLA titanium implants. To cite this article :
Mihatovic I, Becker J, Golubovic V, Hegewald A, Schwarz F. Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Part 2: augmentation using bone graft substitutes.
Clin Oral Impl Res. 23 , 2012; 308–315.
doi: 10.1111/j.1600‐0501.2011.02238.x     

Immunohistochemical analysis of staged guided bone regeneration and osseointegration of titanium implants using a polyethylene glycol membrane

Objectives

This study aimed to immunohistochemically evaluate staged guided bone regeneration and osseointegration of titanium implants using two bone graft substitutes in combination with a polyethylene glycol (PEG) membrane in a dog model.

Materials and methods

Saddle-type alveolar ridge defects were prepared in the lower jaws of 12 foxhounds and randomly filled with a natural bone mineral (NBM) or a biphasic calcium phosphate (SBC) and covered with an in situ gelling PEG membrane. After a healing period of 8 and 12 weeks (six animals each), modSLA titanium implants were inserted to heal in a submerged position. At 8?+?2 and 12?+?2 weeks, respectively, dissected blocks were processed for immunohistochemical analysis [osteocalcin (OC)].

Results

After 8?+?2 weeks, mean OC values (%) tended to be higher in the NBM group (NBM, 32.7?±?8.9 %), but failed to reach statistical significance over the SBC group (SBC, 24.4?±?6.6 %). After 12?+?2 weeks, mean OC values decreased in both groups and was almost identical in both groups (NBM 1.6?±?1.2 %/SBC 2.1?±?1.4 %).

Conclusion

It was concluded that all augmentation procedures investigated were characterised by a comparable OC activity during the process of bone regeneration and osseointegration of modSLA titanium implants.     

Bone regeneration in dehiscence-type defects at non-submerged and submerged chemically modified (SLActive) and conventional SLA titanium implants: an immunohistochemical study in dogs

Objectives: The aim of the present study was to evaluate bone regeneration in dehiscence‐type defects at non‐submerged and submerged titanium implants with chemically modified (mod) and conventional sandblasted/acid‐etched (SLA) surfaces. Material and Methods: Standardized buccal dehiscence defects were surgically created following implant site preparation in both the upper and lower jaws of 12 beagle dogs. Both types of implants were randomly assigned to either a non‐submerged or a submerged healing procedure. After 1, 2, 4, and 8 weeks, dissected blocks were processed for histomorphometrical [e.g. new bone height (NBH), per cent linear fill (PLF), percentage of bone to implant contact (BIC‐D), area of new bone fill (BF)] and immunohistochemical analysis. Results: At 8 weeks, non‐submerged and submerged SLA implants revealed significantly lower mean NBH (1.1±0.8–1.9±1.2 mm), PLF (27.7±20.3–46.0±28.5%), BIC‐D (26.8±10.4–46.2±16.2%), and BF (1.3±0.9–3.4±2.8 mm²) values than respective modSLA implants [NBH (2.6±0.8–4.3±0.1 mm), PLF (64.2±19.4–107.2±4.7%), BIC‐D (67.5±18.8–82.1±14.8%), BF (2.9±1.0–6.7±1.1 mm²)]. Within modSLA groups, significantly highest BF values were observed at submerged implants. Conclusion: It was concluded that (i) modSLA titanium surfaces promoted bone regeneration in acute‐type buccal dehiscence defects and (ii) a submerged healing procedure improved the outcome of healing additionally.     

Stability, marginal bone loss and survival of standard and modified sand-blasted, acid-etched implants in bilateral edentulous spaces: a prospective 15-month evaluation

Objectives: Chemical modification of the already proven sand‐blasted and acid‐etched (SLA) implant had increased its surface wettability and consequent early‐term osseointegration characteristics. The aim of this clinical trial was to compare the stability changes, success, survival, peri‐implant parameters and marginal bone loss (MBL) of the early‐loaded standard (SLA) and modified sand‐blasted, acid‐etched (modSLA) implants. Material and methods: A total of 96 SLA and modSLA implants were placed in a bi‐lateral, cross‐arch position to the jaws of 22 patients. Resonance frequency analysis (RFA) was used to measure the implant stability in the surgery and following healing after 1, 3 and 6 weeks. At the stage of loading, a panoramic X‐ray was obtained and RFA measurement was repeated for all implants. Implants were restored by metal–ceramic crowns and followed for 1 year to determine the success, survival rate, peri‐implant parameters and MBL. Results were compared by one‐ and two‐way ANOVA, log‐rank test and generalized linear mixed models (P<0.05). Results: One modSLA implant was lost after 3 weeks following the surgery yielding to a 100 and 97.91% success rate for SLA and modSLA implants, respectively (P=0.323). At the loading stage, modSLA implants showed significantly lower MBL (0.18 ± 0.05 mm) than SLA implants (0.22 ± 0.06 mm; P=0.002). In the loading stage, RFA value of the modSLA implants (60.42 ± 6.82) was significantly higher than the both implant types in the surgical stage (55.46 ± 8.29 and 56.68 ± 8.19), and following 1 (56.08 ± 7.01 and 55.60 ± 9.07) and 3 weeks of healing (55.94 ± 5.95 and 55.40 ± 6.50 for SLA and modSLA implants, respectively). Conclusions: modSLA implants demonstrated a better stability and a reduced MBL at the loading stage. Both SLA and modSLA implants demonstrated a favorable success and survival at the end of 15‐month follow‐up. To cite this article :
Karabuda ZC, Abdel‐Haq J. Arιsan V. Stability, marginal bone loss and survival of standard and modified sand‐blasted, acid‐etched implants in bilateral edentulous spaces: a prospective 15‐month evaluation.
Clin. Oral Impl. Res. 22 , 2011; 840–849
doi: 10.1111/j.1600‐0501.2010.02065.x     

The effect of SLActive surface in guided bone formation in osteoporotic-like conditions

Objectives: The aim of the study was to evaluate new bone formation under etched titanium (SLA) and modified‐etched hydrophilic titanium (modSLA) domes placed on the calvarium of healthy, osteoporotic and osteoporotic treated with bisphosphonates rabbits. Methods: Experimental osteoporosis was induced by ovariectomy (OV) and calcium‐deficient diet in 24 New Zealand female rabbits. Twelve OV rabbits were treated with weekly dozes of alendronate (Fosamax^®) (B) while 12 OV rabbits received no treatment (O). Another 12 rabbits were sham operated and used as healthy controls (C). At 6 weeks following OV, one modSLA and one SLA titanium dome were placed in the parietal bones of each rabbit. The animals were sacrificed at 30 and 120 days following the dome placement. Various histomorphometric measurements were performed in the most central of the undecalcified sections produced. Results: After 30 days of healing, in the C group, the total bone (TB) area was 37.6% and 37.0% under the modSLA and SLA domes, respectively. In the O group, the TB was 35.7% and 24.8%. In the B group, TB was 37.0% and 32.1%, respectively. After 120 days of healing, in the C group TB was 40.1% and 36.4%, respectively. In the O group, TB was 29.6% and 27.9%, respectively. In the B group, TB was 49.7% and 42.5%, respectively. Hierarchical analysis of variance showed that the type of titanium dome significantly influenced new bone and the amount of new bone being in contact with inner surface of the dome (BIC) independently of the observation period and group (P<0.05). The administration of bisphosphonates influenced the BIC (P<0.05). Conclusion: The use of modSLA surface may promote bone healing and osseointegration in osteoporotic rabbits, whereas administration of bisphosphonates may compromise the osseointegration of the newly formed bone at the early healing period. To cite this article:
Mardas N, Schwarz F, Petrie A, Hakimi A‐R, Donos N. The effect of SLActive surface in guided bone formation in osteoporotic‐like conditions.
Clin. Oral Impl. Res. 22 , 2011; 406–415.
doi: 10.1111/j.1600‐0501.2010.02094.x     

Comparative study of the osseointegration of dental implants after different bone augmentation techniques: vascularized femur flap, non-vascularized femur graft and mandibular bone graft

Objectives: The purpose of this study was to evaluate the osseointegration of the dental implants placed into the mandible augmented with different techniques in pigs. Material and methods: Four adult domestic pigs were used. Horizontal augmentation of the mandible was performed in animals by using vascularized femur flap (VFF), non‐vascularized femur graft (NVFG) and monocortical mandibular block graft (MG). After 5 months of healing 10 dental implants were placed into each augmented site. The pigs were sacrificed after 3 months of healing. Undecalcified sections were prepared for histomorphometric analysis. Results: Mean bone–implant contact (BIC) values for implants placed into MG, NVFG and VFF were 57.38 ± 11.97%, 76.5 ± 7.88%, 76.53 ± 8.15%, respectively. The BIC values of NVFG and VFF group were significantly greater than MG group (P<0.001). On the other hand, there was not statistically significant difference between NVFG group and VFF group (P=0.999). Conclusion: NVFG as well as VFF can be considered as a promising method for augmentation of alveolar defects and the placement of the implants. The selection of non‐vascularized graft or vascularized flap depends on the condition of the recipient site. To cite this article:
Benlidayi ME, Gaggl A, Bürger H, Brandner C, Kurkcu M, Ünlügenç H. Comparative study of the osseointegration of dental implants after different bone augmentation techniques: vascularized femur flap, non‐vascularized femur graft and mandibular bone graft.
Clin. Oral Impl. Res. 22 , 2011; 594–599
doi: 10.1111/j.1600‐0501.2010.02013.x     

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.     

Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: an experimental study in a rabbit model

Aim: The aim of this study was to evaluate the osseointegration of implants placed in areas with artificially created bone defects, using three bone regeneration techniques. Material and methods: The experimental model was the rabbit femur (16), where bone defects were created and implants were placed. The peri‐implant bone defects were filled with a deproteinized bovine bone mineral, NuOss^? (N), NuOss^? combined with plasma rich in growth factors (PRGF) (N+PRGF), NuOss^? covered by an RCM⁶ membrane (N+M), or remained unfilled (control group [C]). After 4 and 8 weeks, the animals were euthanized and bone tissue blocks with the implants and the surrounding bone tissue were removed and processed according to a histological protocol for hard tissues on non‐decalcified ground sections. The samples were studied by light and electron scanning microscopy, histometric analysis was performed to assess the percentage of bone in direct contact with the implant surface and a statistical analysis of the results was performed. Results: In the samples analyzed 4 weeks after implantation, the percentage of bone tissue in direct contact with the implant surface for the four groups were 57.66±24.39% (N), 58.62±20.37% (N+PRGF), 70.82±20.34 % (N+M) and 33.07±5.49% (C). In the samples with 8 weeks of implantation time, the percentage of bone in direct contact was 63.35±27.69% (N), 58.42±24.77% (N+PRGF), 78.02±15.13% (N+M) and 40.28±27.32% (C). In terms of the percentage of bone contact, groups N and N+M presented statistically significant differences from group C in the 4‐week trial test (P<0.05; ANOVA). For the 8‐week results, only group N+M showed statistically significant differences when compared with group C (P<0.05; ANOVA). Conclusion: In conclusion, the NuOss^? granules/RCM⁶ membrane combination presented a percentage of bone contact with the implant surface statistically greater than in the other groups. To cite this article:
Guerra I, Branco FM, Vasconcelos M, Afonso A, Figueiral H, Zita R. Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: an experimental study in a rabbit model.
Clin. Oral Impl. Res. 22 , 2011; 314–322.
doi: 10.1111/j.1600‐0501.2010.02002.x     

Study of the osseointegration of dental implants placed with an adapted surgical technique

Objective: To study the osseointegration of dental implants placed with a modified surgical technique in Beagle dogs and to compare it with the conventional method. Materials and methods: Dental implants were placed bilaterally in the mandible of Beagle dogs using the press‐fit as well as undersized implant bed preparation technique. Micro computer tomography (micro‐CT) and histometric methods were used to analyze the bone implant contact and bone volume (BV) around the implants. Results: The bone‐to‐implant contact percentage (BIC: expressed as %), first BIC (1st BIC: expressed in mm), sulcus depth (SD: expressed in mm) and connective tissue thickness (CT: expressed in mm) were analyzed for both groups. The BIC percentage was significantly higher for the undersized installed implants (P=0.0118). Also, a significant difference existed between the undersized and press‐fit installed implants for the first screw thread showing bone contact (P=0.0145). There were no significant differences in mucosal response (SD and CT) for both installation procedures. Also, no significant difference was found in the BV, as measured using micro‐CT, between the implants placed with an undersized technique (59.3±4.6) compared with the press‐fit implants (56.6±4.3). Conclusion: From the observations of the study, it can be concluded that an undersized implant bed can enhance the implant–bone response. To cite this article:
Al‐Marshood MM, Junker R, Al‐Rasheed A, Al Farraj Aldosari A, Jansen JA, Anil S. Study of the osseointegration of dental implants placed with an adapted surgical technique
Clin. Oral Impl. Res. 22 , 2011; 753–759
doi: 10.1111/j.1600‐0501.2010.02055.x     

Biofunctionalization of titanium implants with a biomimetic active peptide (P‐15) promotes early osseointegration

Objectives: The early stages of peri‐implant bone formation play an essential role in the osseointegration and long‐term success of dental implants. By incorporating bioactive coatings, this biofunctionalization of implant surfaces may enhance the attachment of the implant to the surrounding bone and stimulate bone regeneration. Material and methods: To demonstrate faster osseointegration, the surfaces of dental implants were grit‐blasted and acid‐etched. They were then coated with hydroxyapatite (HA) and experimental implants were further coated with a biomimetic active peptide (P‐15) in one of two concentrations. These biofunctionalized samples and controls with no peptide were placed in the forehead region of 12 adult pigs. Six animals were evaluated for a period of 14 or 30 days. Results: Histomorphometric analysis demonstrated that the implants with the high concentration of P‐15 had significantly higher percentage of bone‐to‐implant contact (BIC) at 14 (P=0.018) and 30 (P=0.015) days compared with the other groups. Both concentrations of P‐15 showed increased peri‐implant bone density compared to the control group at 30 days. Conclusion: Biofunctionalization of the implant surface with a biomimetic active peptide leads to significantly increased BIC rates at 14 and 30 days and higher peri‐implant bone density at 30 days. To cite this article:
Lutz R, Srour S, Nonhoff J, Weisel T, Damien CJ, Schlegel KA. Biofunctionalization of titanium implants with a biomimetic active peptide (P‐15) promotes early osseointegration.
Clin. Oral Impl. Res. 21 , 2010; 726–734.
doi: 10.1111/j.1600‐0501.2009.01904.x     

In vivo performance of zirconia and titanium implants: a histomorphometric study in mini pig maxillae

Objectives: To compare the bone tissue response to surface‐modified zirconia (ZrO₂) and titanium implants. Methods: Cylindrical low‐pressure injection moulded zirconia (ZrO₂) implants were produced with an acid‐etched surface. Titanium implants with identical shape, sandblasted and acid‐etched surface (SLA) served as controls. Eighteen adult miniature pigs received both implant types in the maxilla 6 months after extraction of the canines and incisors. The animals were euthanized after 4, 8 and 12 weeks and 16 zirconia and 18 titanium implants with the surrounding tissue were retrieved, embedded in methylmethacrylate and stained with Giemsa–Eosin. The stained sections were digitized and histomorphometrically analysed with regard to peri‐implant bone density (bone volume/total volume) and bone–implant contact (BIC) ratio. Statistical analysis was performed using Mann–Whitney' U‐test. Results: Histomorphometrical analysis showed direct osseous integration for both materials. ZrO₂ implants revealed mean peri‐implant bone density values of 60.4% (SD ± 9.9) at 4 weeks, 65.4% (SD ± 13.8) at 8 weeks, and 63.3% (SD ± 21.5) at 12 weeks after implantation, whereas Ti‐SLA implants demonstrated mean values of 61.1% (SD ± 6.2), 63.6% (SD ± 6.8) and 68.2% (SD ± 5.8) at corresponding time intervals. Concerning the BIC ratio, the mean values for ZrO₂ ranged between 67.1% (SD ± 21.1) and 70% (SD ± 14.5) and for Ti‐SLA between 64.7% (SD ± 9.4) and 83.7% (SD ± 10.3). For the two parameters investigated, no significant differences between both types of implants could be detected at any time point. Conclusion: The results indicate that there was no difference in osseointegration between ZrO₂ implants and Ti‐SLA controls regarding peri‐implant bone density and BIC ratio. To cite this article :
Gahlert M, Roehling S, Sprecher CM, Kniha H, Milz S, Bormann K. In vivo performance of zirconia and titanium implants: a histomorphometric study in mini pig maxillae.
Clin. Oral Impl. Res. 23 , 2012; 281–286.
doi: 10.1111/j.1600‐0501.2011.02157.x     

Osseointegration and stability of a modified sand-blasted acid-etched implant: an experimental pilot study in sheep

Objective: The aim of this pilot study was to compare the early‐term osseointegration characteristics of standard (SLA) and modified sand‐blasted and acid‐etched (modSLA) implants in an experimental animal model. Material and methods: A total of 30 SLA and modSLA implants were placed to the tibiae of three sheep and the insertion torque value (ITV) and resonance frequency analysis (RFA) measurements were performed. RFA measurement was repeated on 3 and 6 weeks healed implants after which the animals were sacrificed for histomorphometric analysis. Bone‐to‐implant contact was assessed on the non‐decalcified sections. Six weeks healed implants were also subjected to the reverse torque test (RTT). Results were analyzed by the Friedman test, Kruskal–Wallis test and Spearman rank correlation test. Results: All implants reached to a strong primary stability with a mean 36.13 ± 2.47 and 35.47 ± 2.85 N/cm ITV. In the surgical stage, RFA values for SLA and modSLA implants were found to be 72.27 ± 3.17 and 71.6 ± 2.87, respectively. After 3 weeks of healing, mean BIC% (80.64 ± 13.89%) and RFA value (76.8 ± 1.14) of modSLA implants were significantly higher (P=0.0002) than that of SLA implants (64.39 ± 21.2 BIC% and 74.2 ± 4.76 RFA). However, no statistically significant difference between SLA and modSLA implants was recorded after 6 weeks of healing. Both implants revealed similar results in the RTT test (115.2 ± 4.14 and 117 ± 4.47 N/cm for SLA and modSLA implants, respectively). No correlation was found between RFA and BIC%. Conclusion: Within the limits of this pilot study, it can be concluded that modSLA implants achieve a higher bone contact and stability at earlier time points when compared with SLA implants. To cite this article:
Abdel‐Haq J, Karabuda CZ, Arιsan V, Mutlu Z, Kürkçü M. Osseointegration and stability of a modified sand‐blasted acid‐etched implant: an experimental pilot study in sheep.
Clin. Oral Impl. Res. 22 , 2011; 265–274.
doi: 10.1111/j.1600‐0501.2010.01990.x     

Rehabilitation of irradiated patients with modified and conventional sandblasted acid-etched implants: preliminary results of a split-mouth study

Purpose: The aim of this study was to evaluate the success rate of chemically modified and conventional sandblasted acid‐etched surface (SLA) titanium implants in irradiated oral squamous cell carcinoma patients. Material and methods: Twenty patients with a mean age of 61.1 years were treated with dental implants after ablative surgery and radio‐chemotherapy of oral cancer. All patients were non‐smokers. The placement of SLA and modSLA implants was performed bilaterally according to a split‐mouth design. All 102 implants (50 SLA, 52 modSLA) placed showed an unloaded healing time of 6 weeks in the mandible and 10 weeks in the maxilla. Mean crestal bone changes using standardized orthopantomographies and clinical parameters like pocket depths, mPII and mBI were evaluated. Results: Of 102 implants, 55 implants (27 SLA implants, 28 modSLA) were located in the maxilla and 47 implants (23 SLA, 24 modSLA) in the mandible. The average observation period was 14.4 months. The amount of bone loss at the implant shoulder of SLA implants was 0.4 mm mesial and 0.4 mm distal. The modSLA implants displayed a bone loss of mesial 0.3 mm and distal 0.3 mm. Two SLA implants were lost resulting in a success rate of 96%. The success rate of modSLA implants was 100%. Conclusion: Regarding the data found in this investigation, we can conclude that implants with chemically modified and conventional SLA titanium surface show high success rates in irradiated patients. SLA implants with or without a chemically modified surface regardless of the location can be restored with a high predictability of success at least in the short time range observed. To cite this article:
Heberer S, Kilic S, Hossamo J, Raguse J‐D, Nelson K. Rehabilitation of irradiated patients with modified and conventional sandblasted, acid‐etched implants: preliminary results of a split‐mouth study.
Clin. Oral Impl. Res. 22 , 2011; 546–551
doi: 10.1111/j.1600‐0501.2010.02050.x     

The effect of combined delivery of recombinant human bone morphogenetic protein-2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium-phosphate-coated implants on osseointegration

Objectives: The delivery of growth factors for enhanced osseointegration depends on the effectiveness of the carrier systems at the bone–implant interface. This study evaluated the effect of solo and dual delivery of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF₁₆₅) from biomimetically octacalcium phosphate‐coated implants on osseointegration. Materials and methods: Biomimetic implants, bearing either a single growth factor (BMP or VEGF) or their combination (BMP+VEGF), were established, and compared with acid‐etched (AE, control) and biomimetic implants without growth factor (CAP). Implants were placed into frontal skulls of nine domestic pigs. The quality of osseointegration was evaluated using microradiographic and histomorphometric analysis of bone formation inside four defined bone chambers of the experimental implant at 1, 2 and 4 weeks. Results: Biomimetic implants, either with or without growth factor, showed enhanced bone volume density (BVD) values after 2 and 4 weeks. This enhancement was significant for the BMP and BMP+VEGF group compared with the control AE group after 2 weeks (P<0.05). All biomimetic calcium‐phosphate (Ca‐P) coatings exhibited significantly enhanced bone–implant contact (BIC) rates compared with the uncoated control surface after 2 weeks (P<0.05). However, the combined delivery of BMP‐2 and VEGF did not significantly enhance BIC at the final observation period. Conclusion: It was concluded that the combined delivery of BMP‐2 and VEGF enhances BVD around implants, but not BIC. Therefore, it may be assumed that changes in the surface characteristics should be considered when designing growth factor‐delivering surfaces. To cite this article:
Ramazanoglu M, Lutz R, Ergun C, von Wilmowsky C, Nkenke E, Schlegel K A. The effect of combined delivery of recombinant human bone morphogenetic protein‐2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium‐phosphatecoated implants on osseointegration.
Clin. Oral Impl. Res. xx , 2011; 000–000.
doi: 10.1111/j.1600‐0501.2010.02133.x     

Intermittent parathyroid hormone fails to stimulate osseointegration in diabetic rats

Objectives: Diabetes is considered a risk factor in the osseointegration of dental implants, which suggests that these patients might benefit from anabolic therapies. Preclinical studies, including investigations by this research group, revealed that intermittent administration of parathyroid hormone (PTH) stimulates bone formation on the surface of titanium implants under physiological conditions. However, the anabolic effect of PTH on osseointegration under the hyperglycemic condition of diabetes is unknown. Methods: The ability of PTH to stimulate osseointegration was investigated in 40 female Wistar rats that were randomly divided into the following treatment groups: diabetes, diabetes plus PTH, control, and control plus PTH. Diabetes was induced by intraperitoneal injection of streptozotocin (45 mg/kg) at 1 week before implantation. Rats received PTH at a dose of 60 μg/kg or a vehicle by subcutaneous injection starting at the day of implant insertion into the tibia. Histomorphometric analysis was performed after 4 weeks. Results: The medullary peri‐implant bone area significantly increased in rats receiving PTH in comparison with the control group (41±12% to 20±12%; P<0.01). Moreover, there was an increased bone‐to‐implant contact (BIC) area in animals treated with PTH (47±18% to 27±16%; P<0.05). In contrast, diabetic rats failed to benefit from the anabolic treatment. A similar peri‐implant bone area occurred in the diabetes group, independent of treatment with PTH (13±9% to 15±6%; P>0.05). Moreover, PTH did not affect the BIC area under hyperglycemic conditions (16±12% to 16±8%; P>0.05). No significant changes were observed in the cortical compartment of all groups. Conclusion: These results demonstrate that the metabolic characteristics of the diabetic rats produced a condition that was unable to respond to PTH treatment. These findings led us to hypothesize that metabolic control of diabetes might be a critical determinant when diabetic patients are undergoing anabolic therapy to enhance osseointegration. To cite this article:
Kuchler U, Spilka T, Baron K, Tangl S, Watzek G, Gruber R.
Intermittent parathyroid hormone fails to stimulate osseointegration in diabetic rats.
Clin. Oral Impl. Res. 22 , 2011; 518–523
doi: 10.1111/j.1600‐0501.2010.02047.x     

Impact of the outcome of guided bone regeneration in dehiscence-type defects on the long-term stability of peri-implant health: clinical observations at 4 years

Objectives: To investigate the impact of residual defect height (RDH) following guided bone regeneration (GBR) in dehiscence‐type defects on the long‐term stability of peri‐implant health after a period of 4 years. Material and methods: The RDH values in dehiscence‐type defects at titanium implants were clinically assessed after 4 months of submerged healing following augmentation using a natural bone mineral (NBM) and a randomized application of either a cross‐linked‐ (VN) or a native collagen membrane (BG) (n=12 patients each). The RDH values were classified as absent (0 mm, control; n=8), minimal (1 mm, test 1; n=8), or advanced (>1 mm, test 2; n=8). Clinical parameters (i.e. bleeding on probing [BOP], probing pocket depth [PD], mucosal recession [MR]) were recorded (mesio‐, mid‐, and disto‐buccal aspects) at 4 years after prosthesis installation. Results: The mean PD (2.9±0.7, 2.8±0.7, 2.7±0.8 mm) values at 4 years were comparable in all the groups investigated. The mean MR values tended to be increased in both the test groups (0.5±0.7, 0.4±0.6 mm, respectively), when compared with the control group (0.2±0.3 mm) (P>0.05, respectively). The mean BOP values were also increased in both the test groups (45.8±30.5%, 54.1±24.8%, respectively), even reaching statistical significance when comparing test 2 and control (29.1±21.3%) groups (P=0.02). Conclusion: The present study indicated that (i) implants exhibiting RDH values >1 mm are at a higher risk of developing peri‐implant disease and (ii) positive RDH values may be associated with an increase in MR and may therefore compromise the overall esthetic outcome of implant therapy. To cite this article:
Schwarz F, Sahm N, Becker J. Impact of the outcome of guided bone regeneration in dehiscence‐type defects on the long‐term stability of peri‐implant health: clinical observations at 4 years. Clin. Oral Impl. Res 23 , 2012; 191–196.
doi: 10.1111/j.1600‐0501.2011.02214.x     

Local application of the osteogenic inducer sustained-release system promotes early bone remodeling around titanium implants

Enhanced osseointegration and a shortened healing time are required for dental implant treatment. The aim of this study was to evaluate whether topical application of the osteogenic inducer (OI) sustained-release system over the implant promotes early bone remodeling around the implant. The mandibular canines of 15 New Zealand White rabbits were extracted. After 3 months of healing, implants coated with poly(lactic-co-glycolic acid) (PLGA)+OI, PLGA alone, or no material (control) were inserted into the canine sites. After 4 weeks, specimens were harvested from the three groups and evaluated. Implant stability recorded by Periotest revealed significantly higher values for the PLGA + OI group (?2.61 ± 0.43) than for the PLGA (?1.47 ± 0.45) and control groups (?1.08 ± 0.19) (P < 0.001). Moreover, the PLGA+OI group had improved bone volume and structural parameters around the implants at 4 weeks, as shown by significantly increased BV/TV, BSA/BV, Tb.Th, and BIC (P < 0.05), as well as decreased Tb.Sp (P = 0.010) compared with the other groups. The histological results showed more trabecular bone and bone matrix around the implants in the PLGA+OI group. Therefore, local application of the OI sustained-release system might be able to promote early bone remodeling around titanium implants and facilitate faster and better osseointegration.     

Effects of growth hormone on initial bone formation around dental implants: a dog study

Objective: The aim of this study was to evaluate the effects of topical application of growth hormone (GH) on the osteointegration of dental implants in dogs at 5 and 8 weeks after surgery. Materials and methods: Mandibular premolars and molars were extracted from 12 Beagle dogs. Four screw implants were placed in each mandible. Before implant placement, 4 IU of GH were applied to the test sites (TS); no treatment was applied to control sites (CS). Morphometric parameters, bone‐to‐implant contact (BIC), peri‐implant connective tissue, interthread bone and newly formed bone were measured. The Student's t‐test for was used for statistical analysis of data obtained. Results: After 5 weeks of treatment, BIC values varied slightly between 34.33 ± 2.35% (CS) and 35.76 ± 2.96% (TS). Interthread bone tissue was 64.08 ± 8.68 at CS and 72.86 ± 2.93 at TS, with statistical significance (P<0.05). Bone neoformation was 72.53 ± 4.54 at the CS and 80.74 ± 1.65 for the GH group, these being statistically significant differences (P<0.05). After 8 weeks, BIC had slightly increased for the GH group (36.47 ± 3.09 vs. 39.61 ± 2.34). Interthread bone was 80.57 ± 2.28 at the CS and 82.58 ± 2.44 at the GH site, which was statistically significant. Bone neoformation was 88.09 ± 1.38 at CS and 91.01 ± 1.52 at TS, showing statistical significance (P<0.05). Conclusion: Topical application of 4 IU of GH like a biomimetic agent at the moment of implant placement has no significant effects on the BIC at 5 and 8 weeks, although bone neoformation and inter‐thread bone values did increase significantly. To cite this article:
Calvo‐Guirado JL, Mate‐Sanchez J, Delgado‐Ruiz R, Ramirez‐Fernández MP, Cutando‐Soriano A, Peña M. Effects of growth hormone on initial bone formation around dental implants: a dog study
Clin. Oral Impl. Res. 22 , 2011; 587–593.
doi: 10.1111/j.1600‐0501.2010.02007.x     

Osseointegration of dental implants in ectopic engineered bone in three different scaffold materials

The in vivo regeneration of bone flaps might be an alternative to autogenous bone grafting. The first human case of mandibular reconstruction using the greater omentum as a bioreactor was reported in 2016. However, whether engineered bone will support the osseointegration of dental implants has not yet been investigated. In this study, bone tissue engineering was performed in the greater omentum of nine miniature pigs using bone morphogenetic protein 2, bone marrow aspirate, and three different scaffolds: hydroxyapatite, biphasic calcium phosphate (BCP), and titanium. After 8 weeks, two implants were placed in each scaffold; after another 8 weeks, the bone blocks were harvested for radiographic, histological, and histomorphometric analysis. All implants exhibited sufficient primary stability, and the success rate was 100%. The bone-to-implant contact ratios (BICs) were 38.2%, 68.5%, and 42.9%; the inter-thread bone densities were 29.4%, 64.9%, and 33.5%; and the peri-implant bone-scaffold densities were 56.4%, 87.6%, and 68.6% in the hydroxyapatite, BCP, and titanium groups, respectively. The BIC showed a strong correlation (r = 0.76) with the peri-implant bone-scaffold density. This study shows that de novo engineered bone leads to successful osseointegration and therefore may allow implant-based prosthodontic rehabilitation.     

Peri-implant bone reactions to immediate implants placed at different levels in relation to crestal bone. Part I: a pilot study in dogs

Purpose: The aim of the present study was to evaluate bone remodeling and bone‐to‐implant contact (BIC) after immediate placement at different levels in relation to the crestal bone of Beagle dogs. Materials and methods: The mandibular bilateral second, third and fourth premolars of six Beagle dogs were extracted and six implants were immediately placed in the hemi‐arches of each dog. Randomly, three cylindrical and three tapered implants were inserted crestally (control group) and 2 mm subcrestally (experimental group). Both groups were treated with a minimal mucoperiosteal flap elevation approach. A gap from the buccal cortical wall to the implant was always left. Three dogs were allowed a 4‐week submerged healing period and the other three an 8‐week submerged healing period. The animals were sacrificed and biopsies were obtained. Biopsies were processed for ground sectioning. Histomorphometric analysis was carried out in order to compare buccal and lingual bone height loss, and BIC between the two groups. Results: All implants osseointegrated clinically and histologically. Healing patterns examined microscopically at 4 and 8 weeks for both groups (crestal and subcrestal) yielded similar qualitative bone findings. The distance from the top of the implant collar to the first BIC in the lingual crest (A–Lc) showed a significant difference (P=0.0313): 1.91 ± 0.2 mm in the control group and 1.08 ± 0.2 mm in the experimental group. There was less bone resorption in subcrestal implants than crestal implants. The mean percentage of newly formed BIC was greater with the cylindrical implant design (46.06 ± 4.09%) than with the tapered design (32.64 ± 3.72%). Conclusion: These findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri‐implant tissue remodeling. However, less resorption of the Lc may be expected when implants are placed 2 mm subcrestally. To cite this article:
Negri B, Calvo‐Guirado JL, Pardo‐Zamora G, Ramírez‐Fernández MP, Delgado‐Ruíz RA, Muñoz‐Guzón F. Peri‐implant bone reactions to immediate implants placed at different levels in relation to crestal bone. Part I: a pilot study in dogs.
Clin. Oral Impl. Res. 23 , 2012; 228–235.
doi: 10.1111/j.1600‐0501.2011.02158.x