Early implant placement in sites with ridge preservation or spontaneous healing: histologic, profilometric, and CBCT analyses of an exploratory RCT

Abstract

Purpose

The aim of this study was to compare changes in soft and hard tissue and the histologic composition following early implant placement in sites with alveolar ridge preservation or spontaneous healing (SH), as well as implant performance up to 1 year after crown insertion.

Methods

Thirty-five patients with either intact buccal bone plates or dehiscence of up to 50% following single-tooth extraction of incisors, canines, or premolars were included in the study. They were randomly assigned to undergo one of three procedures: deproteinized bovine bone mineral with 10% collagen (DBBM-C) covered by a collagen matrix (DBBM-C/CM), DBBM-C alone, or SH. At 8 weeks, implant placement was carried out, and cone-beam computed tomography scans and impressions were obtained for profilometric analysis. Patients were followed up after the final crown insertion and again at 1 year post-procedure.

Results

Within the first 8 weeks following tooth extraction, the median height of the buccal soft tissue contour changed by −2.11 mm for the DBBM-C/CM group, −1.62 mm for the DBBM-C group, and −1.93 mm for the SH group. The corresponding height of the buccal mineralized tissue changed by −0.27 mm for the DBBM-C/CM group, −2.73 mm for the DBBM-C group, and −1.48 mm for the SH group. The median contour changes between crown insertion and 1 year were −0.19 mm in the DBBM-C/CM group, −0.09 mm in the DBBM-C group, and −0.29 mm in the SH group.

Conclusions

Major vertical and horizontal ridge contour changes occurred, irrespective of the treatment modality, up to 8 weeks following tooth extraction. The DBBM-C/CM preserved more mineralized tissue throughout this period, despite a substantial reduction in the overall contour. All 3 protocols led to stable tissues for up to 1 year.

Graphical Abstract

INTRODUCTION

Alveolar ridge preservation (ARP) is a well-established technique that significantly reduces the degree of ridge resorption following tooth extraction [1,2]. A healing time of 4–6 months after ARP is generally accepted to allow bone formation [3,4,5]. Hence, this technique has primarily been employed for late implant placement protocols. However, early approaches (at 4–8 weeks post-extraction) may also benefit from ARP, as early bone formation is not impeded [6]. Furthermore, it has been suggested that soft tissue healing might also benefit from ARP [7,8].

Early implant placement is typically performed at 4-8 weeks, after adequate soft tissue healing has occurred [9,10,11,12]. This approach allows complete soft tissue healing, while some hard tissue structures of the former socket remain [12,13,14]. Early implant placement is usually performed after spontaneous healing (SH), but generally requires simultaneous guided bone regeneration with implant placement [10]. Recent clinical studies have analyzed the effect of ARP followed by early implant placement at 8 weeks [7,15,16]. Some of these studies have shown a trend towards improved soft tissue conditions, including fewer invaginations and increased volume at the time of implant placement compared to spontaneously healed sites. However, there is limited clinical data on hard tissue behavior at this early stage following ARP. Hard tissue healing at ARP-treated sites has been examined in several clinical trials [17,18,19,20]. The majority of these analyses have focused on delayed implant placement protocols, while only a few clinical studies have investigated hard tissue behavior in the early stages following ARP [6,21,22].

Therefore, the aim of this exploratory randomized controlled clinical study was to compare changes in soft and hard tissue and the histologic composition following early implant placement in sites with ridge preservation or SH, as well as to evaluate and performance of the implants up to 1 year after crown insertion.

MATERIALS AND METHODS

The present exploratory randomized controlled clinical trial included 2 ridge preservation groups and a negative control group (SH). The clinical data up to 8 weeks following tooth extraction have been published earlier [7]. The study was conducted in accordance with the Helsinki Protocol, was approved by the local ethical committee No. 2015-0420 (new: PB_2016-02507), and was registered in the German Register of Clinical Trials (DRKS00009496).

Study population

In brief, patients requiring single-tooth extractions and subsequent early implant placement were consecutively recruited between 2015 and 2018 [7] at the Clinic of Reconstructive Dentistry, University of Zurich, Switzerland. Eligible teeth for the study included those with fractures, chronic apical periodontitis, or root resorption of dental or traumatic origin in the absence of suppuration or acute inflammation. Molar sites were excluded. The exclusion criteria at the time of patient recruitment were systemic diseases, smoking more than 20 cigarettes per day, poor oral hygiene (plaque control record [PCR] >20%), untreated periodontitis, or pregnancy.

Tooth extraction and ridge preservation/SH

Following a screening visit, patients were scheduled for tooth extraction. Before extraction, a sectional A-silicone impression (President, Coltène Whaledent, Alstätten, Switzerland) was taken. After careful tooth extraction, the socket was examined and patients were withdrawn from the study if more than 50% of the buccal bone plate was missing, as measured vertically. At this time point, a sealed envelope was opened containing the following group allocation according to a computer-generated list:

• • DBBM-C/CM: deproteinized bovine bone mineral with 10% collagen (DBBM-C) (Geistlich Bio-Oss^® Collagen, Geistlich Pharma AG, Wolhusen, Switzerland) was placed within or slightly higher than the palatal bone plate in order to optimally support matrix placement. A collagen matrix (CM; Geistlich Mucograft^® Seal, Geistlich Pharma AG) measuring 8 mm in diameter was adapted and sutured to the soft tissue borders using single interrupted sutures (Dafilon No. 6/0, Braun Aesculap, Tuttlingen, Germany).

• • DBBM-C: DBBM-C was placed as described above, and a criss-cross suture was used to stabilize the bone substitute material, without the intention to obtain primary wound closure.

• • SH: no further treatment was applied and the coagulum within the socket was left to heal spontaneously.

Following treatment, a cone beam computer tomography (CBCT) scan was taken (baseline; BL-CBCT) (field of view: 40×40 mm, voxel size: 0.08 mm³, exposure time: 17.5 s, 90 kV, 5 mA) using a 3D Accuitomo 170 scanner (J. Morita Corporation, Tokyo, Japan). All patients received a chlorhexidine mouth rinse for 7 days (0.2% chlorhexidine, Kantonsapotheke, Zurich, Switzerland), analgesics (Mefenacid 500 mg, Streuli Pharma, Uznach, Switzerland) and antibiotics for 5 days (amoxicillin 750 mg 3 times per day, Sandoz, Basel, Switzerland) and were scheduled for a follow-up examination at 7–10 days for a clinical examination and suture removal.

Implant placement

Six weeks after the extraction, all patients underwent a second CBCT scan (6W-CBCT). At 8t weeks, implants were placed according to the early (type 2) implant placement protocol [12]. On the day of implant placement, a second silicone impression was taken before the implant was placed. After flap elevation, a trephine drill with a 1.8 mm diameter was used to obtain a tissue biopsy core in the area of the planned osteotomy for the implant.

Subsequently, the implants were positioned according to the pre-planned restorative placement. If dehiscence or fenestration defects were present, or if the buccal bone plate was thin (<1.5 mm), GBR was carried out, and primary wound closure was achieved. In cases where GBR was not necessary, both transmucosal and submerged healing protocols were utilized. Postoperatively, patients adhered to the same protocol as they did following extraction, which included using antiseptic rinsing solution and taking analgesics and antibiotics when GBR was performed.

Prosthetic treatment and follow-up

Three months after implant placement, patients were reevaluated and treated based on their individual requirements. This included providing a temporary implant crown and refining the emergence profile. All final crowns were secured with screws and composed of zirconium dioxide with minimal veneering (less than 0.5 mm thickness), either as a single-piece custom zirconia abutment or extraorally cemented onto a standard or customized titanium abutment.

One week after the placement of the final restoration (FDPi), and again after one year (1Y), patients were scheduled for follow-up visits. These visits included assessments of the PCR, probing depth, bleeding on probing, and the width of the buccal keratinized tissue. Additionally, a silicone impression and a periapical radiograph were obtained. The thickness of the mucosa was measured using an endodontic file 1 mm below the mucosal margin.

Processing of histologic samples

All collected tissue core samples were fixed in 4% formalin for at least 48 hours. Specimens within the trephine bur were meticulously removed, rinsed under running tap water, trimmed, dehydrated, and infiltrated with xylol. Subsequently, they were embedded in methylmethacrylate without decalcification. Tissue blocks were sectioned into 200-μm-thick vertical slices using a slow-speed diamond saw (VARICUT^® VC-50; Leco, Munich, Germany). These sections were then polished to a final thickness of 80–100 μm (Knuth-Rotor-3; Struers, Rødovre/Copenhagen, Denmark) and surface-stained with toluidine blue [23].

Histomorphometric assessment

All biopsies were evaluated by an assessment team (SB, DT, WZL, and a blinded histologist). Biopsies with a clearly identifiable crestal-to-apical orientation were selected for analysis, and 2 standardized regions of interest were identified in the superficial and central areas of the former extraction socket at ×100 magnification (Leica DM6000 B, Leica, Wetzlar, Germany). Image editing software (Adobe Photoshop CS6 Extended; Adobe Systems, San Jose, CA, USA) was utilized to mark bone substitute, new bone, old bone, and soft tissue. The histomorphometric analysis was conducted using a software program (LAS V4.3, Leica Microsystems, Wetzlar, Germany), and the area fraction of the tissues was subsequently calculated (Figure 1).

Figure 1. Histologic analysis showing (A) a representative complete core biopsy (DBMM-C/CM group), with the apical portion towards the right side. More substitute and more old/new bone can be seen towards the apical area. The superficial (left) and central (central) ROI is marked in green (B) The central ROI at a higher magnification (C) Analysis of the particular ROI with the measurement of the area fraction of new bone, old bone, soft tissue, and background.

DBBM-C/CM: deproteinized bovine bone mineral with 10% collagen covered with a collagen matrix, ROI: region of interest.

Profilometric and radiographic analyses:

Dental casts were created using silicone impressions taken before tooth extraction (BL) and prior to implant placement at 8 weeks (IP), following crown insertion (FDPi), and 1 year after (1Y). These casts were digitized using a scanner (Imetric 3D, Courgenay, Switzerland) to generate standard tessellation language (STL) files.

To evaluate the changes during the 8-week healing period following tooth extraction, a combined analysis using CBCT data and STL files was performed. The DICOM data from BL-CBCT and 6W-CBCT were separately imported into a digital implant planning program (SMOP, Swissmeda AG, Zurich, Switzerland). Next, the STL files from BL and IP were incorporated into each CBCT (Figure 2A and B). A bucco-oral cross-section was chosen, dividing the extraction site into two equal parts. For all vertical measurements, a horizontal line connecting the buccal and oral gingival margins on the BL STL was used as a reference (Figure 3A). For all horizontal measurements, a horizontal line was drawn at the highest point of mineralized tissue, perpendicular to the axis of the extraction socket (Figure 3B).

Figure 2. (A) Overview as well as sagittal, bucco-oral, and axial cross-sections depicting CBCT scans following tooth extraction and the alveolar ridge preservation procedure. The green STL file shows the contour before extraction; the yellow STL file follows the 8-week healing period. (B) The same case with the CBCT before implant placement, again merged with the STL files from pre-extraction and 8 weeks of healing.

CBCT: cone-beam computed tomography, STL: standard tessellation language.

Figure 3. The same patient as presented in Figure 2, showing the profilometric analysis. (A) Vertical measurements, (B) Horizontal measurements.

STT: soft tissue thickness, RW: ridge width.

Vertical measurements (Figure 3A):

• • Mucosabucc: from the buccal mucosal margin in BL STL to the nearest point of IP STL

• • Mucosaoral: from the oral mucosal margin in BL STL to the nearest point of IP STL

• • Bonebucc: from the reference line to the buccal plate (change from BL to 6W)

• • Boneoral: from the reference line to the oral plate (change from BL to 6W)

Horizontal measurements (Figure 3B):

• • RW1, RW3, RW5: ridge width at 1, 3, and 5 mm from the highest point of mineralized tissue (change from BL to 6W)

• • STT1, STT3, STT5: buccal soft tissue thickness at 1, 3, and 5 mm from the highest point of mineralized tissue (change from BL to 6W)

• • Contour1, Contour3, Contour5: buccal contour reduction at 1, 3, and 5 mm from the highest point of mineralized tissue (change from BL to 8W)

In addition, to assess the profilometric changes at the buccal contour throughout the entire observation period, the STL files from BL, FDPi, and 1Y were superimposed. A region of interest was defined at the buccal soft tissue contour to assess the mean distance between surfaces [24,25].

Image analysis software (ImageJ, National Institutes of Health, Bethesda, MD, USA) was used to measure the mesial and distal marginal bone levels (MBLm+d) based on single-tooth X-rays. The implant shoulder (IS) served as a reference and the thread pitch (0.6 mm for Astra Osseospeed EV) was used to adjust the scale. From these measurements, combined (mesial and distal) values were determined, and differences between time points were calculated.

Statistical analysis

Clinical data, along with histologic and volumetric analysis data, were collected in a spreadsheet (Microsoft Excel, Microsoft Corp., Redmond, WA, USA) and subsequently imported into statistical analysis software (SAS Corp., Cary NC. USA). Continuous variables were described using mean, median, standard deviation, quartiles, and range, while counts and percentages were used for categorical variables. The primary outcome was the thickness of the mucosa at 2 months post tooth extraction [7]. Confidence intervals (CIs) were included for relevant parameters. Statistical linear models with interaction terms and interaction plots were generated to examine the impact of dehiscence following tooth extraction in the three groups, as well as the influence of jaw and tooth type (incisor, canine, premolar) on various outcome variables. Due to the small sample sizes of some subgroups, only partial analyses were deemed justifiable.

RESULTS

Initially, a total of 46 patients were screened. Ultimately, 35 patients were analyzed until implant placement (Figure 4), and the characteristics of the study population are illustrated in Table 1. Final restorations were successfully inserted in all patients. Follow-up examinations were conducted for up to 1 year and were analyzed in 31 patients (lost to follow-up: 3; implant loss: 1, SH group) (Figure 4). The overall implant survival rate was 97.14% at the 1-year mark.

Figure 4. Flowchart depicting the entire study period.

DBBM-C/CM: deproteinized bovine bone mineral with 10% collagen covered with a collagen matrix, DBBM-C: deproteinized bovine bone mineral with 10% collagen, SH: spontaneous healing, FDP: fixed dental prosthesis, GBR: guided bone regeneration.

Table 1. Patient characteristics including sex, age, smoking status, and site.

Variables		DBBM-C/CM (n=12)	DBBM-C (n=12)	SH (n=11)	Total (n=35)
Sex
	Male	7 (58.3)	7 (58.3)	3 (27.3)	17 (48.6)
	Female	5 (41.7)	5 (41.7)	8 (72.7)	18 (51.4)
Age (yr)
	Median	66.5	71	64	67
	Q1; Q3	53.0; 71.5	55.0; 74.5	52.0; 71.0	55.0; 72.0
Smokers, <10 cigarettes per day		1 (8.3)	0 (0)	0 (0)	1 (2.9)
Smokers, 10–20 cigarettes per day		0 (0)	2 (16.6)	3 (27.3)	5 (14.2)
Maxillary
	Incisors	4	1	5	10
	Canines	1	1	1	3
	Premolars	4	7	3	14
Mandibular
	Incisors	0	1	0	1
	Canines	0	1	0	1
	Premolars	3	1	2	6
One neighboring tooth		2 (16.7)	6 (50.0)	6 (54.5)	14 (40.0)
Two neighboring teeth		10 (83.3)	6 (50.0)	5 (45.5)	21 (60.0)
Buccal bone dehiscence of 0%–50% after extraction		4 (33.3)	5 (41.7)	2 (18.2)	11 (31.4)
Dehiscence defect type after implant placement		3 (25)	5 (41.7)	5 (45.5)	13 (37.1)
Fenestration defect type after implant placement		0 (0)	0 (0)	2 (18.2)	2 (5.7)
Intrabony defect type after implant placement		1 (8.3)	1 (8.3)	1 (9.1)	3 (8.6)
Guided bone regeneration after implant placement		8 (66.7)	7 (58.3)	10 (90.9)	25 (71.4)

Values are presented as number (%) unless otherwise indicated.

DBBM-C/CM: deproteinized bovine bone mineral with 10% collagen covered with a collagen matrix, DBBM-C: deproteinized bovine bone mineral with 10% collagen, SH: spontaneous healing, Q1: first quartile, Q3: third quartile.

Histology at implant placement

All data can be found in Table 2. In the central area, the median percentage of bone substitute was 10% (95% CI, 4%–22%) for the DBBM-C/CM group and 13% (95% CI, 0%–52%) for the DBBM-C group. In the superficial area, the percentages were lower, with 8% (95% CI, 3%–16%) for DBBM-C/CM and 6% (95% CI, 0%–16%) for DBBM-C. Newly formed bone in the central area constituted 22% (95% CI, 5%–33%) for the DBBM-C/CM group, 37% (95% CI, 8%–61%) for the DBBM-C group, and 35% (95% CI, 4%–53%) for the SH group. In the superficial area, the percentages of newly formed bone were lower, measuring 21% (95% CI, 4%–37%) for DBBM-C/CM, 10% (95% CI, 6%–17%) for DBBM-C, and 33% (95% CI, 0%–88%) for SH. Conversely, the percentage of soft tissue was slightly higher in the superficial area. Due to the small sample sizes, none of the intergroup comparisons yielded significant results.

Table 2. Descriptive results of the histomorphometric analysis.

Group	Area	Variable	N	Mean	SD	Min	Q1	Median	Q3	Max
DBBM-C/CM	Superficial	Bone substitute	6	8%	5%	3%	4%	8%	14%	16%
DBBM-C	Superficial	Bone substitute	8	7%	6%	0%	2%	6%	14%	16%
SH	Superficial	Bone substitute	7	0%	0%	0%	0%	0%	0%	0%
DBBM-C/CM	Superficial	New bone	6	19%	13%	4%	4%	21%	28%	37%
DBBM-C	Superficial	New bone	8	10%	4%	5%	6%	10%	12%	18%
SH	Superficial	New bone	7	37%	29%	0%	16%	33%	58%	88%
DBBM-C/CM	Superficial	Old bone	6	1%	2%	0%	0%	0%	1%	5%
DBBM-C	Superficial	Old bone	8	0%	0%	0%	0%	0%	0%	0%
SH	Superficial	Old bone	7	2%	2%	0%	0%	0%	3%	6%
DBBM-C/CM	Superficial	Soft tissue	6	71%	10%	59%	62%	69%	81%	86%
DBBM-C	Superficial	Soft tissue	8	83%	7%	74%	76%	83%	87%	93%
SH	Superficial	Soft tissue	7	61%	30%	12%	41%	64%	81%	100%
DBBM-C/CM	Central	Bone substitute	6	11%	6%	4%	7%	10%	10%	22%
DBBM-C	Central	Bone substitute	8	17%	18%	0%	2%	13%	25%	52%
SH	Central	Bone substitute	7	0%	0%	0%	0%	0%	0%	0%
DBBM-C/CM	Central	New bone	6	21%	10%	5%	17%	22%	27%	33%
DBBM-C	Central	New bone	8	30%	21%	5%	8%	37%	43%	61%
SH	Central	New bone	7	34%	17%	4%	22%	35%	46%	53%
DBBM-C/CM	Central	Old bone	6	8%	17%	0%	0%	0%	9%	42%
DBBM-C	Central	Old bone	8	1%	2%	0%	0%	0%	0%	4%
SH	Central	Old bone	7	15%	21%	0%	0%	8%	44%	46%
DBBM-C/CM	Central	Soft tissue	6	60%	9%	46%	55%	59%	66%	73%
DBBM-C	Central	Soft tissue	8	52%	12%	39%	42%	49%	64%	68%
SH	Central	Soft tissue	7	51%	28%	2%	33%	56%	58%	96%

N is lower than for other outcomes, as all biopsies without a clearly identifiable crestal-to-apical orientation were excluded.

N: number, SD: standard deviation, Min: minimum, Q1: first quartile, Q3: third quartile, Max: maximum, DBBM-C/CM: deproteinized bovine bone mineral with 10% collagen covered with a collagen matrix, DBBM-C: deproteinized bovine bone mineral with 10% collagen, SH: spontaneous healing.

Profilometric changes (prior to tooth extraction to implant placement)

Vertical changes

During the first 8 weeks following tooth extraction, the buccal soft tissue contour’s height (Mucosabucc) changed by −2.11 mm for the DBBM-C/CM group, −1.62 mm for the DBBM-C group, and −1.93 mm for the SH group (intergroup comparison P=0.495). The Mucosaoral measurements were −1.22 mm for the DBBM-C/CM group, −1.50 mm for the DBBM-C group, and −1.40 mm for the SH group (intergroup comparison P=0.826). In the premolar subgroup, there was a statistically significant difference in the mean Mucosabucc values when comparing the 3 groups (P=0.0253), with group 1 having a significantly lower mean than group 2.

During the first 8 weeks after tooth extraction, the height of the buccal mineralized tissue (Bonebucc) changed by −0.27 mm for DBBM-C/CM, −2.73 mm for the DBBM-C group, and −1.48 mm for the SH group (intergroup comparison P=0.012). The reduction of the oral mineralized tissue (Boneoral) was −0.83 mm for DBBM-C/CM, −0.93 mm for the DBBM-C group, and −1.60 mm for SH (intergroup comparison P=0.513). Interaction modeling did not reveal any statistically significant relationships between the presence of a buccal hard tissue dehiscence following tooth extraction and Mucosabucc or Bonebucc (P>0.10). No differences were observed when comparing the upper and lower jaws.

Horizontal changes

The overall contour (contour1) changed by −0.78 mm (95% CI, −1.13 to −0.16 mm) in the DBBM-C/CM group, −0.69 mm (95% CI, −0.89 to −0.39 mm) in the DBBM-C group, and −0.62 mm (95% CI, −0.87 to −0.22 mm) in the SH group. The reduction at more apical levels followed a similar trend, but the effect was less pronounced (Table 3). No significant differences were identified in terms of jaw or incisors/canines/premolars (P>0.05).

Table 3. Descriptive results of the profilometric analysis based on cone-beam computed tomography scans and standard tessellation language files.

Group	Variable	N	Mean	SD	Min	Q1	Median	Q3	Max
DBBM-C/CM	Bonebucc	12	−0.26	1.21	−3.25	−0.70	−0.27	0.37	1.82
DBBM-C	Bonebucc	12	−2.54	2.37	−6.29	−4.70	−2.73	−0.52	1.06
SH	Bonebucc	11	−2.75	2.73	−8.13	−5.50	−1.48	−0.65	0.22
DBBM-C/CM	Boneoral	12	−0.91	0.91	−2.53	−1.30	−0.83	−0.60	0.64
DBBM-C	Boneoral	12	−1.23	1.93	−6.58	−1.60	−0.93	−0.09	0.66
SH	Boneoral	11	−1.33	1.21	−2.88	−2.20	−1.60	−0.40	1.30
DBBM-C/CM	Mucosabucc	12	−2.28	1.31	−3.89	−3.50	−2.11	−1.08	−0.52
DBBM-C	Mucosabucc	12	−1.72	1.01	−3.74	−2.20	−1.62	−1.00	−0.44
SH	Mucosabucc	11	−1.98	0.94	−3.62	−2.70	−1.93	−1.16	−0.72
DBBM-C/CM	Mucosaoral	12	−1.62	1.23	−4.35	−2.00	−1.22	−0.84	−0.41
DBBM-C	Mucosaoral	12	−1.62	0.78	−2.90	−2.20	−1.50	−1.14	−0.30
SH	Mucosaoral	11	−1.41	0.50	−2.16	−1.80	−1.40	−1.17	−0.48
DBBM-C/CM	RW1	12	−0.70	0.87	−2.93	−0.90	−0.47	−0.13	0.15
DBBM-C	RW1	12	−1.37	3.17	−10.70	−0.90	−0.53	0.23	0.68
SH	RW1	10	−1.69	2.88	−7.24	−4.10	0.04	0.23	0.83
DBBM-C/CM	RW3	12	−0.29	0.73	−1.81	−0.80	−0.02	0.18	0.65
DBBM-C	RW3	12	−0.63	0.82	−2.99	−0.80	−0.61	−0.20	0.19
SH	RW3	11	−0.59	1.99	−6.05	−0.80	0.25	0.53	1.00
DBBM-C/CM	RW5	12	−0.27	0.80	−1.77	−0.50	−0.25	0.14	1.04
DBBM-C	RW5	12	−0.27	0.49	−1.12	−0.70	−0.07	0.10	0.24
SH	RW5	11	−0.04	1.79	−4.76	−0.20	0.18	1.08	1.78
DBBM-C/CM	STT1	12	−0.05	1.01	−2.35	−0.50	0.13	0.67	1.14
DBBM-C	STT1	12	0.11	1.30	−1.83	−0.90	0.26	0.48	3.20
SH	STT1	8	0.75	2.56	−2.63	−0.60	0.20	1.80	5.79
DBBM-C/CM	STT3	11	−0.01	0.92	−1.20	−0.80	0.02	0.74	1.47
DBBM-C	STT3	11	0.22	1.24	−1.54	−0.70	0.13	1.16	2.57
SH	STT3	8	1.09	1.85	−1.20	−0.20	0.68	2.34	4.34
DBBM-C/CM	STT5	9	0.51	1.02	−0.34	−0.20	0.10	0.70	2.88
DBBM-C	STT5	9	0.20	1.73	−1.65	−0.60	−0.09	0.84	4.09
SH	STT5	6	0.77	3.10	−3.75	−1.30	0.88	2.81	5.12
DBBM-C/CM	Contour1	12	−0.77	0.59	−1.82	−1.10	−0.78	−0.29	0.13
DBBM-C	Contour1	12	−0.71	0.59	−2.24	−0.90	−0.69	−0.44	0.15
SH	Contour1	8	−0.67	0.40	−1.48	−0.80	−0.62	−0.39	−0.22
DBBM-C/CM	Contour3	11	−0.57	0.71	−2.00	−1.00	−0.46	−0.26	0.52
DBBM-C	Contour3	11	−0.90	1.79	−4.37	−0.80	−0.44	−0.39	2.03
SH	Contour3	8	0.04	1.44	−1.50	−0.70	−0.49	0.67	2.81
DBBM-C/CM	Contour5	8	0.05	0.65	−0.61	−0.40	−0.03	0.30	1.40
DBBM-C	Contour5	7	−0.56	0.50	−1.48	−0.70	−0.57	−0.33	0.19
SH	Contour5	6	−0.09	2.17	−2.87	−1.10	−0.29	0.23	3.73
DBBM-C/CM	Buccal mean distance Pre-extraction to 1Y	9	−0.97	0.90	−2.42	−1.40	−0.70	−0.40	0.19
DBBM-C	Buccal mean distance Pre-extraction to 1Y	10	−0.71	1.43	−2.33	−1.60	−1.19	−0.33	1.94
SH	Buccal mean distance Pre-extraction to 1Y	9	−1.29	0.90	−3.25	−1.70	−1.06	−0.63	−0.45
DBBM-C/CM	Buccal mean distance FDPi to 1Y	9	−0.20	0.32	−0.66	−0.40	−0.19	−0.13	0.50
DBBM-C	Buccal mean distance FDPi to 1Y	10	0.15	1.07	−0.50	−0.30	−0.09	0.02	3.16
SH	Buccal mean distance FDPi to 1Y	9	−0.25	0.45	−1.17	−0.40	−0.29	0.02	0.30

N: number, SD: standard deviation, Min: minimum, Q1: first quartile, Q3: third quartile, Max: maximum, Bucc: buccal, RW: ridge width, STT: soft tissue thickness, 1Y: 1-year follow-up, FDPi: insertion of fixed dental prosthesis, DBBM-C/CM: deproteinized bovine bone mineral with 10% collagen covered with a collagen matrix, DBBM-C: deproteinized bovine bone mineral with 10% collagen, SH: spontaneous healing.

The ridge width change at 1 mm (RW1) was found to be −0.47 mm (95% CI, −0.93 to −0.08 mm) in the DBBM-C/CM group, −0.53 mm (95% CI, −0.98 to 0.24 mm) in the DBBM-C group, and 0.04 mm (95% CI, −5.47 to 0.37 mm) in the SH group. The buccal soft tissue thickness (STT1) was 0.13 mm (95% CI, −0.70 to 0.71 mm) in the DBBM-C/CM group, 0.26 mm (95% CI, −1.07 to 0.52 mm) in the DBBM-C group, and 0.2 mm (95% CI, −0.84 to 5.79 mm) in the SH group. No significant differences were identified in terms of jaw or incisors/canines/premolars (P>0.05), and the interaction term did not reveal a statistically significant influence of the presence of a buccal hard tissue dehiscence following tooth extraction on contour1/RW1 (P>0.424).

Profilometric changes (prior to tooth extraction to 1 year after crown insertion)

Major changes in the buccal contour were observed from pre-extraction to FDPi, with the DBBM-C/CM group showing a change of −0.54 mm (95% CI, −1.97 to 0.09 mm), the DBBM-C group exhibiting a change of −1.05 mm (95% CI, −1.83 to 0.26 mm), and the SH group presenting a change of −0.83 mm (95% CI, −1.71 to −0.16 mm). The median changes between crown insertion and 1 year were −0.19 mm (95% CI, −0.38 to 0.08 mm) for DBBM-C/CM, −0.09 mm (95% CI, −0.40 to 0.06 mm) for DBBM-C, and −0.29 mm (95% CI, −0.61 to 0.20) for SH. No differences were identified in terms of jaw or incisors/canines/premolars (P>0.05), and the interaction term did not reveal a statistically significant influence of the presence of a buccal hard tissue dehiscence following tooth extraction on the profilometric change (P=0.091).

Marginal bone level changes (crown insertion to 1 year)

All clinical parameters are summarized in Supplementary Table 1. The median marginal bone level at FDPi was −0.14 mm (95% CI, −0.46 to −0.07 mm) for the DBBM-C/CM group, −0.19 mm (95% CI, −0.33 to −0.07 mm) for the DBBM-C group, and −0.28 mm (95% CI, −0.97 to 0.00 mm) for the SH group. The changes observed up to 1 year were 0.07 mm (95% CI, −0.13 to 0.18 mm) in the DBBM-C/CM group, 0.00 mm (95% CI, −0.24 to 0.25 mm) in the DBBM-C group, and −0.05 mm (95% CI, −0.21 to 0.47 mm) in the SH group. Again, no differences were identified in terms of jaw or incisors/canines/premolars (P>0.05), and the interaction term did not reveal a statistically significant influence of the presence of a buccal hard tissue dehiscence following tooth extraction on the marginal bone level (P=0.673).

DISCUSSION

The present randomized controlled clinical trial demonstrated i) increased new bone formation at 8 weeks for SH, ii) a smaller reduction in buccal mineralized tissue in the DBBM-C/CM group, iii) a significant decrease in both horizontal and vertical contours for all three groups within the first 8 weeks, iv) minimal changes in tissue contour between crown insertion and the 1-year follow-up for all groups, and v) stable marginal bone levels in all groups.

Histologically, the primary distinction between the ARP groups and SH was the quantity of newly formed bone at 8 weeks, which was greater for SH. This finding has also been reported in a preclinical study [26]. The placement of DBBM delays socket healing and de novo bone formation, which is therefore predominantly in the apical and lateral borders of the socket and on the surface of the DBBM particles, while SH exhibits early formation of woven bone. In addition, the superficial region of interest contained a larger amount of non-mineralized tissue in all groups, which is consistent with the general understanding of extraction socket dynamics [27]. Human biopsies of ARP procedures at early time points are rare, but they are in accordance with the present study, as over 50% of the biopsied areas consisted of non-mineralized tissue [6]. However, a study with re-entry at 4.5 months reported a higher amount of mineralized tissue [4]. It can be concluded that new bone formation is in a very early stage in the present study, which aligns with the clinical experience of having mineralized tissue and DBBM particles embedded within a connective tissue matrix.

The number of sites requiring GBR at implant placement was lower in the ARP groups [7]. Additionally, there were fewer dehiscences in the SH group after tooth extraction, which may have slightly reduced the need for bone augmentation procedures. Interestingly, particularly in light of the current histological findings, it might have been possible to perform even fewer GBR procedures in the ARP groups. The soft material containing early mineralized tissue and DBBM particles is often removed and replaced by a new GBR procedure, as it is clinically impossible to determine whether this material will continue to mineralize. This might be unnecessary, as the present histological results indicate that early bone formation was present in the ARP biopsies. A preclinical study also reported that biomaterials can be left in situ and the implants will osseointegrate [28]. However, it remains a clinical challenge during surgery to distinguish which parts of the soft materials will continue to mineralize and which will not. Additionally, this further complicates implant placement. This can be considered a disadvantage of a protocol that combines ARP with early implant placement. The advantages of the ARP protocol included a reduced number of GBR procedures and an increased soft tissue thickness at the center of the implant site in the DBBM/C-CM group [7].

The CBCT analysis showed a smaller decrease in buccal mineralized tissue in the DBBM-C/CM group compared to the other two groups within the first 8 weeks. However, when considering the overall contour, including the soft tissue, a similar reduction was observed in all three groups. Thus, it is hypothesized that during this early stage, the DBBM-C/CM group was able to preserve more buccal mineralized tissue compared to the other groups, while maintaining a similar overall contour. This has been previously described in early implant placement protocols [12,14]. Even though the buccal bone experienced a reduction at the 8-week re-entry following SH, the soft tissue contour remained relatively intact, and as a result, the soft tissues were considered thick at this time point. However, these findings somewhat contrast with the increased mucosa thickness observed for the DBBM-C/CM group, which was measured at the center of the site [7]. This discrepancy may be further explained by an imbalance in baseline parameters, which becomes evident when comparing absolute values instead of reported changes. The mean vertical distance from the gingival margin of the extracted tooth to the top of the bone crest was nearly twice as high in the DBBM-C/CM group, indicating that many patients in this group had reduced heights of buccal plates, while the soft tissue level remained relatively intact. From this perspective, the applied procedure effectively preserved the overall volume, and the increased soft tissue thickness can be accounted for.

The observed patterns of horizontal soft and hard tissue reduction mainly followed the trends as described in other studies [5,29,30]. Interestingly, significant changes were also observed in the oral aspect, both horizontally and vertically (Figures 2 and 3). While this finding may not be critical for clinical practice, given the region’s minimal esthetic importance, it is a noteworthy discovery for future research. This is because it indicates that the oral structures near the extraction socket are not a reliable reference for buccal measurements, as previously assumed in other studies.

Considering the results up to one year after the placement of the final crown, the performance of all 3 groups was nearly identical. With reference to the buccal volume prior to tooth extraction, the DBBM-C/CM group displayed the smallest reduction; however, all 3 groups maintained stable volumes throughout the follow-up period. The marginal bone levels were favorable, stable, and consistent with findings from other studies [31], and the clinical parameters indicated healthy peri-implant tissues.

This was an exploratory study with a new clinical protocol for 1 of the groups (DBBM-C) and with implant placement and evaluation of the outcomes of ARP at a new early time point. However, the small sample size contributed to an imbalance in certain parameters following tooth extraction, making it challenging to interpret the results.

All three protocols resulted in stable tissues, favorable bone levels, and a high survival rate for the implants up to 1 year. Significant vertical and horizontal ridge contour changes occurred, regardless of the treatment modality, up to 8t weeks following tooth extraction (implant placement). Despite a substantial reduction in the overall contour, the DBBM-C/CM group preserved more mineralized tissue throughout this period.

SUPPLEMENTARY MATERIAL

Supplementary Table 1

Descriptive results of the clinical measurements from crown insertion (FDPi) and 1-year follow-up (1Y)