Healing of Bio-Oss® grafted marginal gaps at implants placed into fresh extraction sockets of incisor teeth in dogs: a study on the effect of submerged vs. non-submerged healing.

Ehsan Mellati Stephen Chen Helen Davies Wayne Fitzgerald Ivan Darby

Authors’ affiliations: Ehsan Mellati, Stephen Chen, Ivan Darby, Periodontics, Melbourne Dental School, University of Melbourne, Parkville, Victoria, Australia Helen Davies, Wayne Fitzgerald, Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia

Healing of Bio-Ossâ grafted marginal gaps at implants placed into fresh extraction sockets of incisor teeth in dogs: a study on the effect of submerged vs. non-submerged healing

Key words: bone healing, dogs, extraction socket, grafting, immediate implant

non-submerged, submerged Abstract Objectives: To evaluate the effect of submerged vs. non-submerged (NS) protocols in healing outcomes of grafted marginal defects of immediate implants.

Corresponding author: Ivan Darby Melbourne Dental School, University of Melbourne 720 Swanston Street, Carlton, Victoria 3053, Australia Tel.: +61 3 9341 1471 Fax: +61 3 9341 1599 e-mail: [email protected]

Materials and methods: The second maxillary incisors were extracted bilaterally in six greyhound dogs. Bone level reduced diameter implants were installed into the extraction sockets leaving orofacial gaps of 2 mm wide. Defects were filled with Bio-Ossâ and covered with Bio-Gideâ. On the one side, the flap was advanced to fully submerge the implant, and on the other, the flap was sutured to allow NS healing. After 3 months of healing, the dogs were sacrificed and block biopsies were obtained to perform histological and morphometric analysis. Results: All implants were clinically healthy and well integrated into bone. In the majority of the specimens, the original bone in the coronal 2–3 mm of the buccal crest had completely resorbed and was replaced by a regenerated bone wall consisting of Bio-Ossâ particles surrounded by newly formed bone. Horizontal and vertical resorption of the buccal bone resulted in ≥1 mm exposure of the implant surface in one-third of implants. Minor differences existed in some aspects of hard tissue healing between submerged and NS. Conclusion: There was very little difference in healing outcomes as well as modelling of the facial bone wall between the submerged and NS protocols in relation to immediate implant placement in this dog model.

Date: Accepted 3 June 2014 To cite this article: Mellati E, Chen S, Davies H, Fitzgerald W , Darby I. Healing of Bio-Ossâ grafted marginal gaps at implants placed into fresh extraction sockets of incisor teeth in dogs: a study on the effect of submerged vs. non-submerged healing. Clin. Oral Impl. Res. 00, 2014, 1–10. doi: 10.1111/clr.12442

The original implant treatment protocol recommended that the implant should be placed in a fully healed site and covered with mucosa after placement to ensure osseointegration (Br anemark et al. 1969, 1977; Adell et al. 1981). The rationale was partly to protect the implant site from bacterial contamination and also to avoid loading of the implant. At a later stage of therapy, a second surgical procedure to connect an abutment had to be performed to expose the implant into the oral cavity (Adell et al. 1981). In contrast to this second stage of submerged surgical protocol, it has been demonstrated that a first stage or non-submerged (NS) approach can lead to successful and predictable osseointegration (Buser et al. 1990, 1997; Schr€ oeder et al. 1990; Buser & von Arx 2000; Ferrigno et al. 2002). Moreover, similar amounts of crestal bone preservation have

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

been reported for both healing approaches in the medium term (Astrand et al. 2002; Cecchinato et al. 2004, 2008; H€ammerle et al. 2012; Cordaro et al. 2013). For immediate implants placed into fresh extraction sockets (Type-1 implant placement), several investigators have demonstrated that NS implants with or without GBR heal predictably and the reported healing outcomes appeared to be similar to the findings of the studies using a submerged approach (Lang et al. 1994; Br€agger et al. 1996; H€ammerle et al. 1998; H€ammerle & Lang 2001; Cornelini et al. 2004; Chen et al. 2007). However, direct comparisons of the submerged and NS healing protocols are scarce. Cordaro et al. (2009) published the first study comparing these two healing protocols and showed that mean radiographic interproximal crestal bone resorption did not

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Mellati et al Submerged and non-submerged grafted immediate implants

differ between groups. Shibly et al. (2012) reported that at 1 year, a slightly better but not statistically significant radiographic outcome was observed for NS healing compared to submerged healing. A disadvantage for the submerged group was significantly higher chance of coronal displacement of mucogingival junction which in certain cases needed to be corrected by mucogingival surgery postoperatively. Clinical studies based on intraoral radiography are limited by the inability to measure hard tissue alterations at the facial aspect of implants, particularly at the crestal region of the socket, where bone defects typically occur following type-1 implant placement. There are currently no histomorphometric studies designed to compare the effect of submerged and NS healing on hard tissue alterations at the facial surfaces of immediate implants. Therefore, the aim of this study was to histologically evaluate the influence of healing protocols on hard tissue alterations of the facial surface of immediate (type-1) implants grafted with deproteinized bovine bone mineral (DBBM). This study also aimed to assess the suitability of the maxillary lateral incisors in the canine model for immediate implant studies.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

Material and methods Clinical procedures

The study protocol was approved by the animal ethics committee of the University of Melbourne (ethics ID no. 1112309.1). Six healthy female greyhound dogs, each weighing about 30 kg and aged 1–2 years, were used. Half an hour prior to induction, sedation was achieved by subcutaneous administration of 0.4 mg ACPâ (acepromazine maleate 2 mg/ml; Delvet, Seven Hills, NSW, Australia). A 22 g intravenous catheter was placed into the foreleg cephalic vein for the administration of peri-operative fluids and the induction agent. General anaesthesia was then induced via a slow full bolus administration of 2 mg/kg Alfaxanâ (alfaxolone 10 mg/ml; Jurox, Rutherford, NSW, Australia). Intubation was carried out with an 11mm cuffed endotracheal tube connected to a gaseous anaesthetic machine delivering oxygen at 2 l/min. Once the respiratory system was isolated, Isorraneâ (isoflurane USP 100%; Baxter Healthcare, Old Toongabbbie, NSW, Australia) was delivered at concentration of 2% and was then maintained at concentration of 1.5%. Isotonic saline fluids were delivered intravenously via the cephalic

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Clin. Oral Impl. Res. 0, 2014 / 1–10

Fig. 1. Clinical photographs of surgical procedures. (a) Pre-operative view, (b) raising a mucoperiosteal flap from 3I to I3, (c) extraction of 2nd incisors and insertion of implants with the shoulder flush with the buccal crest, (d) placement of a closure screw on the submerged side and a healing abutment on the non-submerged (NS) side, (e) filling the peri-implant gap with of Bio-Ossâ, (f) covering the grafting material and buccal bone with Bio-Gideâ, (g) suturing the flap to allow submerged and NS healing, (h) 1-month post-operative view showing submerged and NS healing of implant sites.

catheter at 300 ml/h. Local anaesthesia was provided via infra-orbital nerve block by administration of Lignocaineâ (lignocaine HCL, 20 mg/ml; Troy Laboratories, Glendenning, NSW, Australia). Scaling with an ultrasonic scaler was performed prior to the surgery if plaque and calculus were present at the maxillary incisors area (Fig. 1a). An intrasulcular incision was performed from distal of the right third maxillary incisor (3I) to the distal of left third maxillary incisor (I3). This was followed by vertical releasing incisions bilaterally at disto-buccal line angles of 3I and I3. A mucoperiosteal flap was then raised to allow visualization of the buccal bone (Fig. 1b). The second maxillary incisors were extracted using luxators and forceps. As the roots of

these incisors are flat in a bucco-lingual direction, extreme care was undertaken to minimize disruption of the architecture of the alveolus and trauma to the buccal bone. Following successful delivery of the tooth, the depth and bucco-lingual width of sockets as well as the thickness of crestal bone at the mid-buccal point were measured using a Michigan O probe with Williams markings (Hu-Friedy, Chicago, IL, USA) and recorded by rounding off the measurements to the nearest half a millimetre. Sockets were cleaned of any remnants of soft tissue and checked for any possible dehiscence and/or fenestration of the buccal bone. Osteotomy was initiated at the apico-palatal aspect of the socket and completed in accordance with manufacturer’s recommendation



(Straumann Dental Implant System, Straumann, Basel, Switzerland) to house an 8-mm long and 3.3-mm wide implant. A Straumann Roxolidâ NC implant with SLActiveâ surface was installed in the prepared osteotomy with the shoulder of the implant placed flush with the buccal bony crest (Fig. 1c). Primary stability was achieved by engaging the apical, palatal and proximal bone walls. Using the same periodontal probe, the width and the depth of the intrabony peri-implant defect were measured at mid-buccal point from the implant shoulder to the nearest half a millimetre (Fig. 2). Randomization was performed by tossing a coin for each dog to determine the side to be submerged. A closure screw (Straumann NC, H0, Ti) was connected to the implant on the side to be submerged, and a healing abutment (Straumann NC, conical D3.6, H3.5, Ti) was installed on the contralateral side (Fig. 1d). The peri-implant defect was then filled with DBBM (0.25–1 mm particles, Bio-Ossâ; Geistlich, Wolhusen, Switzerland) (Fig. 1e). A resorbable collagen membrane (Bio-Gideâ; Geistlich) was placed to cover the grafted area and the buccal bone (Fig. 1f). Periosteal releasing was performed, and the flap was coronally advanced to achieve tension-free primary closure using 4-0 synthetic bio-resorbable sutures (Monosynâ; B. Braun, Melsungen, Australia). At the submerged side, the buccal flap was advanced

Fig. 2. Schematic representation of a buccolingual cross section of the implant immediately after placement showing the measurements of the width and depth of the peri-implant defect at the mid-buccal point.

sufficiently to fully cover the implant. However, on the contralateral side, the flap was sutured around the neck of the healing abutment allowing NS healing (Fig. 1g). Post-operative care included subcutaneous administration of non-steroidal analgesic Tergiveâ (Caprophen 50 mg/ml; Parnell Laboratories, Alexandria, NSW, Australia) for post-recovery analgesia and intramuscular administration of antibiotic Duplocillinâ (procaine 150 mg/ml and benzathine 115 mg/ ml; Intervet, Bendigo East, Vic, Australia). Within the first 2 weeks, wounds were inspected daily and a plaque control regimen including once daily application of Hexarinseâ (chlorhexidine gluconate supported by cetylpyridinium chloride and zinc gluconate; Virbac, Regents Park, NSW, Australia) was provided. This was followed by gentle mechanical brushing of the implant site, and the adjacent teeth with a soft toothbrush soaked in Hexarinseâ three times a week for the rest of the experimental period. Soft food was prescribed in the first week followed by a normal diet thereafter. At 3 months (Fig. 1h), all six dogs were sacrificed using an intravenous injection of Lethabarbâ (pentobarbitone; Virbac). Histological preparation

The pre-maxillae of the dogs were resected en bloc and immediately placed in 10% buffered formalin (Orion, Balcatta, WA, Australia). The specimens were then sent to Cell Tissue Analysis laboratory (Freiburg, Germany) for histological processing. The fixated bone blocks were dehydrated in a series of graded ethanol solutions with increasing concentration (70%, 80%, 90% and 100% ethanol), remaining in each concentration for 1 day. Defatting was carried out by soaking the biopsies in xylene (Merck, Darmstadt, Germany) for 24 h. Specimens were then infiltrated and embedded in resin (Technovit 9100; Heraeus Kulzer, Wehrheim, Germany) and polymerized according to the manufacturer’s instructions. After polymerization, radiographs were taken to determine the position of each implant to ensure sectioning was parallel to the long axis of the implant. Samples were then cut in a bucco-lingual direction using a low-speed rotary diamond saw (MicrosliceTM; Metals Research, Cambridge, UK). Two central sections of 500 lm thickness were obtained from each implant. Sections were mounted onto opaque acrylic slides (Maertin, Freiburg, Germany) and ground and polished to a final thickness of approximately 60 lm on a rotating grinding plate (Stuers, Ballerup, Denmark). Subse-


quently, sections were stained with azure II and pararosaniline (Merck) and examined under a standard light microscope for histological analysis. Histomorphometric measurements

Imaging was performed with an Axio Imager M1 microscope equipped with a digital AxioCam HRc camera (Carl Zeiss, G€ ottingen, Germany). The following landmarks were identified on each slide (Fig. 3):

• • • • •

•

IS: implant shoulder S: surface of the implant at the buccal aspect C: crest of the regenerated buccal bone fBIC: the first bone-to-implant contact OC: the final outer contour of the remodelled buccal bone, ignoring those superficial particles of Bio-Oss that were not in contact with bone and were only embedded in soft tissue ROB: the most coronal remnants of the original buccal bone as stained light magenta

Subsequently, the following measurements were performed: IS-fBIC: representing the level of the most coronal bone-to-implant contact IS-C (vertical distance): representing the level of regenerated crestal bone in relation to implant shoulder

• •

Fig. 3. Histometric landmarks. IS, implant shoulder; S, white line showing the surface of the implant at the buccal aspect; C, crest of the regenerated buccal bone; fBIC, first bone-to-implant contact; OC, final outer contour of remodelled buccal bone; ROB, the most coronal remnants of the original buccal bone (taken from dog #3).

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Imaging System, M€ unster, Germany). Percentage of BIC was also calculated within each area of interest. Differences in the percentage of BIC and percentage of new bone formation in area 1 best described the differences in healing protocol by minimizing the effect of difference in the 3-D shape of defects. Data analysis

(a)

(b)

Fig. 4. (a) Four areas of interest around each implant (area 1–4). Newly formed bone (NB) and Bio-Oss (BO) are stained dark magenta, old bone (OB) is stained light magenta, and soft tissue is stained blue (undecalcified ground sections stained with azure II and pararosaniline; original magnification 950). (b) Labelling for histomorphometric purposes: Bio-Oss granules (green), newly formed bone (red) and older bone (yellow) [taken from dog #2].

•

C-fBIC (vertical distance): representing the depth of the residual intra-bony defect IS-ROB (vertical distance): representing the magnitude of vertical resorption of the original buccal bone S-OC (horizontal distance): representing the final thickness of the remodelled buccal plate after 3 months of healing. This thickness was measured along the entire length of implant at nine levels 1 mm apart, starting from the implant shoulder to the most apical part of implant. Magnitude of horizontal resorption of the crestal bone: as the implant shoulder was placed flush with the buccal crest, the amount of horizontal resorption of the crestal bone was calculated by subtracting the final thickness of the remodelled buccal plate at shoulder level (S-OC at level 0) from the “combined defect and crestal bone width” at baseline.

• •

•

To evaluate the percentage of bone-toimplant contact (BIC) and the quality of the bony tissue around implants, four areas of

interest were determined around each implant (Fig. 4a). This was carried out by drawing 2 mm lines buccally and palatally perpendicular to the implant surface starting at the implant shoulder. The end points of these lines were then connected to a parallel line starting from the most apical part of the implant surface. Each of the two resultant buccal and palatal spaces was then divided into two apical and coronal halves, resulting in a total of four areas of interest (areas 1–4) (Fig. 4b). Given the 8 mm height of the implant, this resulted in an area of interest of 2 9 4 mm at the bucco-coronal half of the implant (area 1). The other three areas of interest (areas 2–4) would also demonstrate the potential influence of healing protocol on healing outcome of bucco-apical, palato-coronal and palato-apical areas of the implant, respectively. Coverage of each tissue component (newly formed bone, remnants of original bone, residual grafting material and non-mineralized tissue) was calculated as the percentage of the total tissue surface (Fig. 4b) using the analysis FIVETM software (Soft

As there were two sections per implant, the average value of the two measurements for each parameter was calculated to represent that implant as the experimental unit. These figures were then used to calculate the mean values and standard deviations of each of the measured parameters for submerged and NS group of implants separately (n = 6). The null hypothesis was that these two healing protocols yield similar healing outcome. Related samples Wilcoxon signed-rank test was used to calculate the P value (Minitab 15; Minitab Inc, State College, PA, USA). The level of significance was set at 0.05.

Results Clinical observations

Following extraction, all sockets were found to be intact with no fenestration or dehiscence present. After 3-months of healing, all implants were clinically stable with no signs of biological or technical complications. During histological processing, no artefacts occurred and no tissue blocks were destroyed. Hence, the test and control sites each yielded six specimens. Baseline data for each dog including the depth and width of extraction sockets, thickness of crestal bone at mid-buccal point, depth and width of the periimplant defect were included in Table 1. There was no statistical difference between the submerged and NS sides in any of the baseline parameters. The depth and width of the extraction sockets were very similar in all dogs with a mean of 11 and 6.33 mm,

Table 1. Measurements (mm) of the baseline parameters for each dog Depth of socket

Dog 1 Dog 2 Dog 3 Dog 4 Dog 5 Dog 6 Mean SD Median IQR

Width of socket

Thickness of crestal bone

Defect width

Defect depth

NS

S

NS

S

NS

S

NS

S

NS

S

12 13 10 10 11 10 11 1.26 10.5 2.25

12 12 10 10 11 11 11 0.89 11 2

7 7 6 6 6 6 6.33 0.51 61

6 7 6 7 6 6 6.33 0.51 61

0.5 0.5 0.5 0.5 0.5 0.5 0.5 0 0.5 0

0.5 0.5 0.5 1 0.5 0.5 0.58 0.20 0.5 0.13

2 2 2 2 2 2 20 20

2 2 2 2 2 2 20 20

10 10 10 10 10 6 9.33 1.63 10 1

12 9 7 6 10 9 8.3 2.13 9 3.75

NS, non-submerged side; S, submerged side.

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respectively. Thickness of mid-buccal point of the crestal bone was consistently about 0.5 mm, except in the submerged side of dog number 4, which was thicker and amounted to about 1 mm. By careful placement, the width of peri-implant defects at the mid-buccal aspect of all implants was maintained consistently at 2 mm, while the depth of defects varied between 6 and 12 mm. Considering the similar depth of sockets, variations in peri-implant defect depth could be due to slightly different angle of implant placement in relation to the 3-dimensional shape of the socket.

specimens, the original bone in the coronal 2–3 mm of the buccal crest had completely resorbed. This was replaced by a regenerated bone wall consisting of Bio-Ossâ particles surrounded by newly formed bone. The regenerated bone crest was located at varying distances from the implant shoulder. The orofacial thickness of the regenerated bone crest was less than the original orofacial dimension of the “combined defect and bone wall thickness”. In the majority of sites, a shallow infra-bony defect was present between the implant surface and the regenerated buccal bone crest.

Histological observations

Morphometric analysis

The histological outcomes following implant placement in both experimental groups were similar. Healing was characterized by integration of the implants which were in close proximity to the original bone on the lingual, lateral and apical aspects of the implant. On the buccal aspect, regenerated bone consisting of Bio-Ossâ particles and newly formed bone filled the gap between the buccal socket wall and the implant. For all specimens, no Bio-Ossâ particles were observed to be in direct contact with the implant surface; an intervening layer of newly regenerated bone was always present. In the majority of the

The level of first bone-to-implant contact (IS-fBIC) was calculated for each implant and is depicted in Table 2. The mean distance of fBIC to implant shoulder was 1.40 0.60 mm for the NS group and 0.66 0.71 mm for the submerged group. This difference was not statistically significant (P = 0.074). In two of the six implants in each group, the regenerated bone crest was located apical to the implant shoulder. The mean distance between the implant shoulder and crest of the regenerated buccal bone (IS-C) was similar in both groups (Table 2).

The mean vertical distance of regenerated buccal crest to the first bone-to-implant contact (C-fBIC) was statistically significantly higher for the NS group (0.92 0.45 mm vs. S: 0.18 0.17 mm) (P < 0.05) (Table 2). The magnitude of the vertical resorption of the original buccal bone (IS-ROB) amounted to about 3.5–4 mm, regardless of the healing protocol (NS: 3.80 2.82 mm vs. S: 3.52 2.08). Although the magnitude of this resorption was highly variable between dogs (range from 0.5 to 9 mm), it was much less variable within each dog. The least vertical resorption of the original buccal crest (0.5 mm) was observed at the site which had the thickest buccal crest at baseline (1 mm buccal crest thickness, Dog 4, submerged side) (Table 2). The final thickness of the remodelled buccal bone after 3 months of healing at different levels from the implant shoulder is presented in Table 3. Overall, no significant statistical difference was found between experimental groups in mean thickness of regenerated buccal bone at any of the levels from the implant shoulder (Table 3). The magnitude of horizontal resorption of the crestal bone was calculated by subtracting the final thickness of buccal bone at shoulder level from the “combined defect

Table 2. Morphometric analysis of healed implant sites IS-fBIC


IS-C

C-fBIC

IS-ROB

NS

S

NS

S

NS

S

NS

S

1.1 1.5 2.0 0.5 1.2 2.1 1.40 0.60 1.35 1.1

0 0.7 0.1 0.3 1.9 1.0 0.66 0.71 0.5 1.15

0 0 1.1 0 0 1.8 0.48 0.78 0 1.3

0 0 0 0 1.6 1 0.43 0.70 0.15 1.15

1.1 1.5 0.9 0.5 1.2 0.3 0.92 0.45

0 0.4 0.1 0.3 0.3 0 0.18 0.17

9.0 4.3 2.0 1.3 2.1 4.1 3.80 2.82 3.1 3.65

6.4 3.3 2.0 0.5 4.6 4.3 3.52 2.08 3.8 3.4

IS, implant shoulder; C, crest of regenerated buccal bone; fBIC, first bone-to-implant contact; ROB, remnants of original buccal bone; NS, non-submerged side; S, submerged side.

Table 3. Final thickness of the remodelled buccal plate at different levels from the implant shoulder for each dog Final thickness of the buccal plate Mean SD

Dog 1

Dog 2

Dog 3

Dog 4

Dog 5

Dog 6

Distance from implant shoulder (mm)

NS

S

NS

S

NS

S

NS

S

NS

S

NS

S

NS

0 1 2 3 4 5 6 7 8

1.1 1.3 1.4 1.6 1.7 1.8 2 2 1.8

0.6 1.4 2.2 2.7 3.3 3.4 3.3 3.4 3.5

0.4 1.4 1.9 2 2.3 2.5 2.8 2.9 2.6

0.2 1 1.7 2.1 2.4 2.6 2.7 2.8 2.5

0 0 2.5 3 3.3 3.4 3.5 3.2 2.5

1 1.7 2.3 2.7 3.1 3.1 3.1 2.9 2.1

1 2.1 2.4 2.6 2.9 3 2.7 2.3 1.8

2.2 2.4 2.4 2.3 2.3 2.2 1.7 0.9 0.4

1 1.9 2.4 3 3.5 3.4 3.2 2.7 2.1

0 0 1.9 2.5 2.8 2.9 2.7 2.4 1.9

0 0 0.2 1.4 1.8 1.9 1.8 1.5 1

0 0 1.3 1.9 2.3 2.4 2.1 1.8 1.2

0.58 1.12 1.8 2.27 2.58 2.67 2.67 2.43 1.97

Median IQR S

0.51 0.91 0.89 0.7 0.76 0.71 0.66 0.62 0.58

0.67 1.08 1.97 2.37 2.7 2.77 2.6 2.37 1.93

NS

0.85 0.96 0.42 0.33 0.43 0.45 0.6 0.89 1.07

0.7 1.2 2.15 2.3 2.6 2.75 2.75 2.5 1.95

S

1.0 2.0 1.3 1.45 1.6 1.53 1.33 1.1 0.93

0.4 1.2 2.1 2.4 2.6 2.75 2.7 2.6 2.0

1.3 1.9 0.7 0.65 0.85 0.83 1.15 1.45 1.75

NS, non-submerged side; S, submerged side. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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Table 4. Magnitude of horizontal resorption of buccal crest at the implant shoulder level Horizontal resorption of crestal bone (mm)

Nonsubmerged

Submerged


1.4 2.1 2.5 1.5 1.5 2.5 1.91 0.51 1.8 1.03

1.9 2.3 1.5 0.8 2.5 2.5 1.91 0.67 2.1 1.18

and crestal bone width” at baseline. Based on the data presented in Table 1, the “combined defect and crestal bone width” was consistently about 2.5 mm (2 mm HDD + 0.5 mm thickness of bony crest) except for the submerged side of Dog 4 which amounted to about 3 mm (2 mm HDD + 1 mm thickness of bony crest). The results of the calculations are summarized in Table 4 and reveals that both experimental groups had a very similar amount of mean horizontal resorption of the crestal bone (NS: 1.91 0.51 mm vs. S: 1.91 0.67 mm). The least horizontal resorption of the crestal bone was again seen in the submerged side of dog number 4 that had the thickest crestal bone, or the largest “combined defect and crestal bone width” at baseline. The mean values for thickness of the remodelled buccal bone at different levels from implant shoulder are depicted diagrammatically in Fig 5. The contour of the resultant buccal bone was similar between the two treatment groups. Furthermore, the extent of horizontal resorption in

Fig. 5. Diagram showing the mean thickness of remodelled buccal plate (X axis) at different levels from the implant shoulder (Y axis) and its relation to original buccal bone. The mean position of the buccal bone at the time of extraction and implant placement is also depicted.

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the coronal 3–4 mm of the implant compared to the original buccal bone position was similar between the two treatment groups. The percentage of new bone formation within each area of interest is presented in Table 5. There was no statistical difference between the submerged and NS healing protocols in any of the areas of interest. The percentage of BIC for each area of interest is summarized in Table 6. Although submerged healing resulted in 15% more BIC within area 1, this difference did not reach statistical significance. Other areas of interest also showed no statistical difference in % BIC.

Discussion Marginal gaps are frequently present around immediate implants and in most cases need to be treated with bone grafting or membranes. It is therefore relevant to question whether NS healing of implants placed in extraction sockets can be as successful as submerged implants. This is particularly important as due to limited availability of soft tissues, achieving complete closure at the time of immediate implant installation is not always easy or even possible. Even if primary closure can be attained, the required coronal advancement of the flap can lead to a narrow width of keratinized gingiva and potential functional and aesthetic concerns in some patients (Shibly et al. 2012). Considering that submerged healing also has the disadvantage of requiring the second stage procedure, it can be stated that if NS healing is proved to have no negative effect on healing of the grafted marginal defects at immediate implants, it might be a more desirable approach than submerged protocol for both the patient and the clinician. It should be noted that in the submerged approach, in clinical practice, the membrane usually extends over the implant and is tucked under the palatal flap. While this can be a potential benefit for the submerged approach, healing outcomes could be influenced by the enhanced barrier effect of the membrane; and thus, the effect of the healing protocol cannot properly be evaluated. To keep the study design standardized, we used the membrane in a similar manner for both submerged and NS sides. In the present experimental model, regenerated osseous tissue consisting of particles of Bio-Ossâ embedded in newly regenerated bone was seen to fill the gap between the implant and the buccal socket wall. This

confirmed the data reported by Ara ujo et al. (2011). However, in both experimental groups at a level close to the implant shoulder, there was high frequency of Bio-Ossâ particles surrounded by connective tissue and not embedded into newly formed bone. This observation was not reported by Ara ujo et al. (2011) in a lower premolar canine model. One speculation for the observed difference can be that resorption of the buccal wall in this upper incisor model was faster, thereby leaving the Bio-Ossâ particles unsupported and more prone to micro-movements. More recent studies by Favero et al. (2013a,b) have shown similar findings. The mean level of the first bone-to-implant contact (fBIC) at the mid-buccal aspect of the NS implants was 1.40 0.6 mm which was almost double that of the submerged group. There were wide standard deviations, and the difference did not reach statistical significance (P = 0.074). However, it is not known whether this implies a true lack of difference or the difference was not statistically significant due to low numbers of specimens. The difference may represent the formation of a biological width around the NS implants. If a true difference exists, one potential implication would be the higher chance of complications for the NS group if biofilm forms on this exposed part of the implant. Interestingly, the level of the fBIC in the NS group of our study was located more apically than that reported by Ara ujo et al. (2011) in a lower premolar canine model. While they also used NS healing, had similar gap width (1–2 mm) and filled the defects with BioOssâ Collagen, their corresponding figure after 6 months of healing was 0.1 0.5 mm. Ara ujo et al. (2006a) have shown that the BIC that was established during the early phase of socket healing at 4 weeks was partially lost as the buccal bone wall underwent continued resorption. Hence, it may be reasonable to speculate that the marked difference in level of fBIC between our study and Ara jo et al. (2011) might be due to the faster u and more pronounced resorption of buccal plate in this maxillary incisor model compared to the lower premolar model. This may lead to lack of support for the bulk of provisional connective tissue matrix and woven bone that has formed within the gap, resulting in its gradual collapse and a more apical level of fBIC. As mid-buccal recession is a common finding in immediate implants (Chen et al. 2007; Evans & Chen 2008; Chen & Buser 2009), it is important to evaluate the vertical dimensional changes of the mid-buccal



Table 5. Percentage of new bone formation within each area of interest for each dog Area 1

Area 2

Area 3

Area 4

% New bone formation

NS

S

NS

S

NS

S

NS

S


27.55 25.85 27.8 39.8 34.8 9.85 27.6 10.18 27.68 14.2

44.3 28.55 31.15 34.35 18.4 22.45 29.86 9.14 29.85 15.4

42.6 35.4 24.8 25.55 30.4 21.3 30 7.88 27.98 13.27

36.2 32.1 24.35 19 24.2 23.5 26.55 6.33 24.27 10.75

19.35 18.25 13.65 12.65 19 18.85 16.95 2.99 18.55 5.69

9.4 20.45 13.9 12.7 19.3 22.4 16.35 5.09 16.6 9.06

45.95 23.95 18.05 26.75 38.6 27.05 30.05 10.26 26.9 17.96

20.25 29.7 27.9 16.65 29.35 25.45 24.88 5.32 26.67 10.09

NS, non-submerged; S, submerged.

Table 6. Percentage of bone-to-implant contact (BIC) within each area of interest for each dog Area 1

Area 2

Area 3

Area 4

% BIC

NS

S

NS

S

NS

S

NS

S


55.95 43.6 28 68.65 52.25 29.7 46.35 15.78 47.92 29.85

54.75 57.05 78.6 53.25 51.35 72.55 61.25 11.4 55.9 21.29

69.2 86.6 71.4 52.65 71.8 53.8 67.57 12.72 70.3 21.37

79.65 68.6 64.3 35.6 40.9 53.65 57.11 16.9 58.97 31.79

84.05 82.85 56.1 72.25 56.1 77.1 71.4 12.59 74.67 27.05

73.6 82.9 52.35 61.25 64.8 65.5 66.73 10.49 65.15 16.54

75.1 60.95 38.25 53.4 75.25 63.1 61 14.01 62.03 25.52

68.95 75.4 53 59.6 54.55 72.75 64.04 9.59 64.29 19.25

NS, non-submerged; S, submerged.

aspect of the crestal bone (IS-C). In one-third of implants, the regenerated buccal crest at mid-buccal point was apical to the implant shoulder, and this distance was ≥1 mm. Interestingly, this observation appeared to be irrespective of the healing protocol, indicating that despite grafting of the peri-implant defects, the regenerated bone does not always extend to the implant shoulder. Similar findings were reported experimentally (Caneva et al. 2011, 2012) and clinically (Gher et al. 1994; Chen et al. 2007). Ara ujo et al. (2006a) has demonstrated that buccal crestal bone resorbs by about 1 mm within 4 weeks following extraction and immediate implant placement. The same authors also suggested that during the process of modelling of the outer portion of the crest region, the Bio-Ossâ particles may be dislodged from the newly formed bone resulting in the change of the profile of the ridge of the grafted sites and small reduction of its dimensions (Ara ujo et al. 2008). It is therefore tempting to speculate that due to the rapid loss of buccal crestal bone in the current model, Bio-Ossâ particles were no longer securely retained within bony walls and thus were unable to retain the original height of the ridge. In the present study, the coronal 2–3 mm of the original crestal bone on the buccal

aspect completely resorbed in majority of implants in both experimental groups. This indicates that loss of original buccal bone occurs even with grafting and irrespective of the healing protocol. The observation that the least amount of vertical resorption of the original buccal bone occurred in the site that had the thickest crest at baseline confirms the findings of previous studies (Ara jo et al. 2005, 2006b; Chen et al. 2007; u Tomasi et al. 2010; Barone et al. 2011) that thinner bone walls undergo more vertical resorption. While all of the implants in the NS group showed some degree of residual intrabony defect, this was observed in four of the six submerged implants. Existence of residual defects of varying dimensions was also reported by other authors in both submerged (Caneva et al. 2011) and NS healing conditions (Ara ujo et al. 2011; Caneva et al. 2012). In our study, these defects (C-fBIC) were found to be significantly deeper in the NS group than the submerged group (P < 0.05) with the mean difference of about 0.8 mm. It can, therefore, be suggested that submerged healing resulted in closer adaptation of the regenerated bone to the implant surface at the coronal part of the implant and may represent the formation of a biological width around the NS implants.


The orofacial thickness of the final buccal bone was less than the “combined defect and bone wall thickness” at baseline, and this was more pronounced at the coronal parts. This observation confirms the data from the animal studies on ridge preservation (Nevins et al. 2006; Ara ujo & Lindhe 2009) and grafted immediate implants (Ara ujo et al. 2011; Barone et al. 2011; Caneva et al. 2012; Favero et al. 2013a,b,c) showing that horizontal resorption will occur despite grafting of extraction sockets or the peri-implant defects. However, it should be noted that here, we compared the baseline measurements, which were recorded using a periodontal probe, to histometric measurements. According to our data, the thickness and outline of the remodelled buccal bone were not affected by the choice of healing protocol. Similar numbers of implants in both groups (33%) demonstrated no crestal bone at the shoulder and at 1 mm below the shoulder level. These data suggest that even after grafting the marginal gaps, coronal buccal bone may still be very thin or completely absent in a considerable number of immediate implants. The observation that the least amount of horizontal crestal resorption was found in the site that had the thickest crestal bone or the largest “combined defect and bone wall width” at baseline corroborates the

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findings of previous studies (Ara ujo et al. 2006b; Ferrus et al. 2010; Sanz et al. 2010; Tomasi et al. 2010). The size of the area of interest #1 was chosen based on the observation that in all samples, the peri-implant defect width was about 2 mm and the peri-implant defect depth was consistently well above 4 mm. Thus, the chosen area size of 2 9 4 mm at the coronal half of the mid-buccal aspect of each implant included the defect at the time of implant placement which was similar in shape and configuration, fully confined by the bony walls and the implant surface, and was filled with Bio-Ossâ and covered with Bio-Gideâ in all samples. The other three areas of interest (#2–4) were also analysed to evaluate whether apical vs. coronal or buccal vs. palatal bone behaved any differently in histologic parameters of bone healing. The mean percentage of the surface area occupied by new bone in each of the areas of interest was closely similar in both experimental groups revealing that new bone formation was not affected by the healing protocol. The wide standard deviation of the data within each animal, however, would suggest that other factors than the healing protocol might be responsible for the observed differences. The least percentage of new bone formation was seen in area three (apico-palatal aspect) which can be explained by the fact that this part of the implant was located mostly within trabecular bone at the time of implant placement. The percentage of new bone formation at the other three areas of interest was more or less the same suggesting that grafting did not enhance new bone formation. This is in agreement with previous reports on ridge preserved extraction sockets (Ara ujo et al. 2008; Ara ujo & Lindhe 2009) and grafted marginal gaps at type-1 implants (Caneva et al. 2012). In the present experiment, the percentage of BIC at different areas of interest ranged from 46% to 71%. Caneva et al. (2012) reported 77% at their non-grafted and 79% at their grafted sites. As the maxillary bone generally contains more marrow and less lamellar bone compared to mandibular bone, this difference is likely to be the result of utilizing maxillary sites in our study as opposed to mandibular sites in the Caneva et al. (2012) study. While %BIC was more similar between experimental groups within area 3 and 4, a higher discrepancy could be detected at area 1 and area 2 between the submerged and NS healing. Although this difference did not reach statistical significance due to wide standard deviations, the

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submerged healing showed a mean increase of 15% and 10% within areas 1 and 2, respectively. This suggests that submerged healing may improve the osseo-integration at the buccal aspect of immediate implants. At the Eighth European workshop on Periodontology, pre-clinical in vivo studies in implant dentistry were comprehensively reviewed (Berglundh & Stavropoulos 2012), and it was reported that intraoral experimental models dominated in monkeys, dogs and mini-pigs; the most common intraoral model was the dog’s mandible. Recently, de Santis et al. (2011) successfully utilized the upper second incisor of Labrador dogs as a model to study bone regeneration at immediate implants. While the authors did not report on their rationale for their choice of tooth/site, several potential advantages can be assumed for such a model in immediate implant studies. Firstly, compared to that of the dog’s mandibular premolars, the size of the dog’s maxillary incisors appears to be more similar to human incisor teeth. Secondly, mandibular premolars in dogs are two-rooted teeth, and thus, the presence of interradicular bone rather than the interdental bone between the adjacent sockets may influence the results in immediate implant studies. Thirdly, the lower premolar model has the disadvantage of requiring an “extra procedure” of sectioning the roots and root canal treatment of the root to be left in-situ. Last but not least, considering that most of the immediate implant studies are aiming to assess factors that could affect the aesthetic outcomes in the anterior maxilla, utilizing mandibular bone which has different tissue composition (Lindhe et al. 2013) and embryonic origin to maxillary bone, and thus, can behave differently may lead to conclusions that do not necessarily apply to the maxillary bone. In this context, utilizing maxillary incisors in those breeds of dogs where maxillary incisors are similar in size to human incisors appears to have advantages. The average orofacial width of mandibular premolar extraction socket in Beagle dogs (Ara ujo et al. 2006b), Labrador dogs (Caneva et al. 2012) and Foxhound dogs (Calvo-Guirado et al. 2014) is 3.8, 4 and 4.3 mm, respectively. These dimensions are clearly less than that of humans. We observed that in our greyhound maxillary incisor model, the width of the extraction sockets was 6.33 0.51 mm and the depth of sockets was 11 1.05 mm, confirming that the current canine’s upper incisor model closely resembles human upper incisors extraction

sockets. The corresponding figures in Labrador dogs were reported to be 5.9–6.4 and 13.7–13.8 mm, respectively (de Santis et al. 2011). Based on the observation that in both our study and de Santis et al. (2011) study no major complication occurred during the healing phase and that dogs tolerated the procedure well, we suggest using this model in immediate implant studies instead of the commonly used mandibular premolar model. In conclusion, within the limits of this study, it can be stated that minor differences may exist in some aspects of hard tissue healing (e.g. depth of residual infra-bony defects, level of the fBIC and the percentage of BIC within the coronal half of the implant) between submerged and NS immediate implants with grafted marginal gaps. Even if these minor discrepancies do not result in meaningful and clinically relevant differences in the short term, their effect on long-term success of immediate implants (e.g. susceptibility to peri-implant diseases) warrants further investigation. In this context, the potential influence of continued remodelling on the outcome of the current observation should be taken into consideration. Furthermore, the current canine’s maxillary second incisor model appears to be a viable alternative and perhaps a preferred model in the study of immediate implants, especially when factors affecting the aesthetic outcomes are being investigated.

Acknowledgements: This project was supported by a grant from the ITI Foundation for the Promotion of Implantology, Switzerland. Bone graft material and membranes were kindly provided by Geistlich Pharma AG (Wolhusen, Switzerland). Authors would like to thank Dr Heiner Nagursky and Ms Annette Linder (Cell Tissue Analysis laboratory, Universit€ats klinikum, Freiburg, Germany) for their expertise in preparation and processing of the histological specimens.

Conflict of interests The authors report no conflict of interest.

Source of funding The study was funded by a grant from the ITI.



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