Abstract
Background
The stability of soft and hard tissues surrounding the implant is not only a matter of aesthetics, but also affects the long-term stability of the implant. The present study was to explore the influence of buccal mucosa width/height (W/H) ratio, emergence profile and buccal bone width on peri-implant soft and hard tissue changes in the posterior region.
Methods
Fifty-eight posterior implant restoration cases were recruited in this study. Evaluations were performed at the time of restoration placement (T0), and 1 year later (T1). Buccal mucosa width (BMW), buccal bone width (BBW), implant buccal inclination angle, and emergence angle were evaluated. The variables that may affect buccal mucosa recession (MR) as well as vertical bone loss (VBL) were analyzed.
Results
The BMW at baseline was 2.93 ± 1.01 mm. The BBW at baseline was 1.50 ± 0.82 mm. The buccal mucosa W/H ratio at 1 year (1.23 ± 0.38) was significantly lower than that at baseline (1.42 ± 0.45). Buccal MR was − 0.22 ± 0.47 mm while VBL was 0.81 ± 0.80 mm. The correlation between MR and initial BMW (r=-0.381), initial W/H ratio (r=-0.422), BBW (r=-0.290) was statistically significant. The correlation between VBL and initial BMW (r=-0.421), initial W/H ratio (r=-0.305), implant buccal inclination angle (r = 0.507), BBW (r=-0.556) was statistically significant.
Conclusions
Within the scope of this study, implant sites in the posterior region presenting a thin BMW, a thin BBW, and a small W/H ratio are more prone to exhibit buccal mucosa recession and vertical bone loss.
Keywords: W/H ratio, Buccal mucosa width, Mucosa recession, Vertical bone loss
Background
In the past, the main parameter for the success of implant therapy was osseointegration. Today, osseointegration stability is still crucial, but more attention is shifting to the health and aesthetics of peri-implant soft tissues. Resorption of buccal bone plate and secondary mucosa recession is a major problem that affects the long-term stability of the implant, which is equally important in the anterior and posterior regions [1, 2]. The average buccal mucosa recession around a single implant is 0.5–1 mm during the 1-year observation period [3, 4]. Cardaropoli et al. evaluated the dimensional changes of peri-implant tissue between implant placement and the second stage of surgery in the maxillary anterior region [5]. An average reduction of 0.4 mm in buccal bone width (BBW) and 0.7 mm in buccal bone height was observed, accompanied by an average buccal mucosa recession of 0.6 mm.
Soft and bone tissues remodeling around the implant are two critical points that need to be addressed, which are influenced by a combination of factors, including the amount and quality of soft and hard tissue, restoration- and implant-related factors [6, 7]. In the concept of peri-implant phenotype proposed by Wang et al. in 2020, mucosa width and supracrestal mucosal height are two important factors for the maintenance of peri-implant health, function, and esthetics [8, 9]. Wennström proposed the hypothesis of a free gingiva “biological height-to-width (W/H) ratio” of 1.5:1 around natural teeth [10]. Recent studies paid attention to the ratio of peri-implant buccal mucosa width (BMW) and supracrestal mucosa height, which has been proved to influence the marginal gingival level [11]. A randomized controlled clinical study by our team proposed that a biological W/H ratio of 1.3:1 around implant is effective in maintaining the marginal gingival level when the initial soft tissue thickness is greater than 2 mm [12].
When designing a restoration, the mucosa W/H ratio can be adjusted by the emergence profile of the restoration. It has been demonstrated that proper design of the emergence profile is essential for the maintenance of soft tissues [13–15]. In order to quantify the emergence profile, the concept of emergence angle was proposed and defined as “the angle between the average tangent of the transitional contour and the tooth long axis” [16, 17]. Our team innovatively proposed a method to measure emergence angle on digital impression data, which resulted in a more convincing value that took the level of soft tissue into account.
The contour of soft tissue was determined by the underlying bone structure. Therefore, the position of the buccal mucosal margin was influenced by the buccal crest level and thickness. Buser et al. emphasized the importance of sufficient BBW (at least 1 mm) and height to obtain long-term peri-implant stability [18]. Yoda et al. recommended an initial BBW of at least 1.5 mm [19]. Spray et al. reported that sites presenting an initial BBW of at least 2 mm at 0.5 mm apical to the crest exhibited a lower rate of vertical bone loss and slightly lower implant failure rate [20]. However, more studies are needed to establish a minimum threshold of bone thickness necessary to achieve predictable peri-implant tissue stability, esthetics, and health.
In summary, there are many factors that seem to influence the level of peri-implant hard and soft tissue. While some of these factors have been well-studied, many remain controversial or unexplored. The present study was to explore the influence of BMW, BBW, buccal mucosa width/height (W/H) ratio, and emergence profile on peri-implant soft and hard tissue changes in the posterior region.
Methods
Patients inclusion protocol
The study was a prospective cohort study with a database derived from part of a previously published prospective randomized controlled study [12]. The study was authorized by the Ethics Committee of Peking University Hospital of Stomatology (approval number PKUSSIRB-201840189). This trial was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn), the number is ChiCTR1900022101. The inclusion and exclusion criteria were as follows. Inclusion criteria: (1) adult patients (20–80 years old); (2) one missing molar tooth; (3) no need of soft or hard tissue augmentation before or during implant placement. Exclusion criteria: (1) any condition that precluded oral surgery, including systemic diseases and gestation period; (2) severe bone or soft tissue defects in the operative region; (3) poor oral hygiene. The study adhered to the STROBE guidelines for reporting clinical trials.
Surgical and prosthetic procedures
Stringent surgical and prosthetic protocols were followed. A full-thickness flap was elevated to expose the surgical site. Initial buccal bone width (the buccal bone width at 1 mm below the crest) was measured with a caliper after preparing the hole. The implant with a 1.0-mm machined neck (Thommen Medical AG, Grenchen, Switzerland) was inserted into the prepared sites using a standardized surgical procedure. All implants were placed with 0.5 mm of the machined neck below the alveolar crest level. Healing abutments were installed on the implants, and the flaps were sutured to accommodate the healing abutments.
Three months after surgery, the implant level impression was taken. The crown was made of zirconia, which was 3 mol% Y2O3 stabilized tetragonal zirconia polycrystal (3Y-TZP-LA, Dental Direkt, Germany). The zirconia crown was fabricated and cemented on titanium abutments extraorally using the Dual-curing resin (3 M RelyX U200). Representative clinical and radiographic photographs are shown in Fig. 1. Before transferred into patients’ mouth, the definitive restorations were screwed into implant analogs and scanned using intraoral scanner (3Shape Trios, 3Shape, Copenhagen, Denmark). The stereolithography (STL) data of the restorations were obtained (STL1). Then the definitive restorations were delivered. Digital impressions were obtained immediately after loading using intraoral scanner to obtain the STL data of baseline digital model (STL2).
Fig. 1.
Representative clinical case. a Preoperative intraoral photograph. b Measurement of the buccal bone width. c The implants were placed with 0.5 mm of the machined neck below the alveolar crest level. d Intraoral photograph after 3 months of implant healing. e The occlusal view of implant-supported zirconia crown. f The buccal view of implant-supported zirconia crown. g radiographic photograph after crown loading
Follow-up and data collection
The patients were called back one year after the restoration delivery. A second digital impression and Cone beam CT (CBCT) was performed for the patients. The STL data obtained from the digital impression at follow-up was marked as STL3. The CBCT data was imported into the Materialise’s interactive medical image control system (MIMICS, Materialise, Belgium) and converted to STL data (STL4).
Data processing and measurement
All the STL files were exported to an image analysis software (Geomagic Qualify 2014; 3D Systems, Rock Hill, SC, USA), and superimposed together. A cylinder shape was established in the restoration STL data (STL1) by “best-fit” to the implant analog. The center axis of the cylinder was defined and recorded as implant long axis (line O). The occlusal plane and implant buccal reference plane were constructed in the baseline digital model (STL2). The midpoints of two central incisors and the proximal mesiobuccal cusps of the two first molars were recorded and lined up to form the occlusal plane (Plane O). The midpoints of mesial and distal contact area of the implant crown were indicated in the digital model. The plane across these two points and perpendicular to the occlusal plane was recorded as implant buccal reference plane (Plane B). The angle between the implant long axis and the buccal reference plane was measured and recorded as the implant buccal inclination angle (IBA). The above plane and angle measurements are shown in Fig. 2.
Fig. 2.
Digital model superimposition and management. a The central axis (Line O) was established by the “best-fit alignment” to the implant analog. Plane O was defined by the midpoints of two central incisors and the proximal mesiobuccal cusps of the two first molars. Plane B was defined by the plane across the midpoints of mesial and distal contact area of the implant crown and perpendicular to the occlusal plane. b The implant buccal inclination angle (IBA) was defined by the angle between the implant long axis and the buccal reference plane
The buccal zenith of the implant site was identified in the initial digital model (STL2). The measurement plane was defined by implant long axis and the buccal zenith point. A transverse section was made along the measurement plane in superimposed digital models (STL1-4). The emergence angle (EA), buccal mucosa width (BMW) and height (BMH) of baseline and at one year were measured in this section (Fig. 3). The buccal vertical bone height was measured as the distance from the crest of the alveolar ridge to the implant platform. Buccal vertical bone loss (VBL) was defined as the difference between the buccal vertical bone height at one year and at baseline. The W/H ratio at baseline and at one year was then calculated separately.
Fig. 3.
The schematic diagram for the analysis of soft and hard tissue alterations. a Measurement of the buccal mucosa width (W) and height (H). b Measurement of buccal bone width (BBW). c Measurement of emergence angle (EA). Line O: the implant long axis. Line A: the tangent line of the restoration at the most coronal point of the buccal mucosa
Explication of clinical parameters
The following clinical parameters were explicated in order to reach a consensus in the study design and implementation.
Occlusal plane: the plane formed by the midpoint of two central incisors and the proximal mesiobuccal cusps of the two first molars.
Implant buccal reference plane: the plane across the midpoints of mesial and distal contact area of the implant crown and perpendicular to the occlusal plane.
Implant buccal inclination angle (IBA): the angle between the implant and the buccal reference plane.
Buccal mucosa width (BMW): the mucosa width at mid-buccal of implant on the implant platform plane.
Buccal mucosa height (BMH): the mucosa height above implant platform at mid-buccal of the implant.
Buccal mucosa W/H ratio: quantitative value calculated from buccal mucosa width (W) and height (H).
Buccal bone width (BBW): the width of the alveolar bone 1 mm below the crest of alveolar ridge at mid-buccal of the implant.
Emergence angle (EA): the angle between tangent line of the restoration at the most coronal point of the buccal mucosa and implant long axis.
Statistical analysis
Statistical analysis was performed by SPSS 20.0 software. Quantitative data were expressed as means and standard deviation (mean ± SD). The Shapiro–Wilk test served to test the normal distribution of the variables. The difference of the buccal mucosa W/H ratio between 1 year and baseline was analyzed by Student’s t test. The differences of buccal mucosa recession/vertical bone loss among the three groups were analyzed by the analysis of variance (ANOVA). Pearson’s correlation analysis was used for normal distributed values with a linear coherence. All P values are bilateral and considered statistically significant if P < 0.05.
Results
Fifty-eight patients were consecutively recruited from patients with missing posterior teeth receiving implant restoration from March 1st 2019 to April 1st 2022 at the 4th Division of Peking University School and Hospital of Stomatology. Six recruited patients withdrew during the study. In the end 52 patients (24 male, 28 female) with 57 implants with a mean age of 47 years (range 22–63 years) completed all study phases and were included in the final analysis. The baseline characteristics of the patients are shown in Table 1.
Table 1.
Description of the demographic and clinical data of the study sample
Variables | Descriptive statistics |
---|---|
Number of patients | 52 |
Female/Male | 28/24 |
Age in years (mean ± SD) | 47.94 ± 11.79 |
Maxilla/Mandible | 12/45 |
Number of implants | 57 |
Clinical parameters
As shown in Table 2, the buccal mucosa W/H ratio at 1 year (1.23 ± 0.38) was significantly lower than the W/H ratio at baseline (1.42 ± 0.45). The implant buccal inclination angle was 2.67 ± 9.06 degrees. The emergence angle at baseline was 36.7 ± 13.7 degrees. The BMW at baselines was 2.93 ± 1.01 mm. The BBW at baseline was 1.50 ± 0.82 mm. Buccal mucosal recession (MR) at T1 was − 0.22 ± 0.47 mm while buccal vertical bone loss (VBL) at T1 was 0.81 ± 0.80 mm. The mean ± SD and range of these variables are presented in Table 3.
Table 2.
Mucosal height and width measurements and their ratio (W/H)
T0 | T1 | |||||
---|---|---|---|---|---|---|
H (mm) | W (mm) | W/H | H (mm) | W (mm) | W/H | |
Value | 2.17 ± 0.74 | 2.93 ± 1.01 | 1.42 ± 0.45 | 2.39 ± 0.87 | 2.82 ± 1.07 | 1.23 ± 0.38a |
T0, before loading; T1, one year after loading. H, buccal mucosa height; W, buccal mucosa width
aThe W/H ratio at T1 was significantly different from T0
Table 3.
Measurements used for analysis
Variables | Mean ± SD | Range |
---|---|---|
Implant buccal inclination angle (deg.) | 2.67 ± 9.06 | −13.03-29.79 |
Emergence angle (deg.) | 36.66 ± 13.68 | 9.28–71.6 |
Buccal alveolar bone width (mm) | 1.50 ± 0.82 | 0.41–4.03 |
Change of mucosa height (mm) | −0.22 ± 0.47 | −1.45-1.12 |
Buccal marginal bone loss (mm) | 0.81 ± 0.80 | −0.37-3.19 |
Association between continuous variables and buccal MR / VBL
The association between each variable and buccal MR is shown in Table 4. Buccal MR was categorized into three groups:<0, 0–0.5, and >0.5 mm. The initial mucosa W/H in the group with buccal mucosal growth was significantly greater than that in the groups with buccal mucosal recession. Other variables including initial BMW, initial mucosa height, implant buccal inclination angle, emergence angle, and BBW were not significantly associated with buccal MR.
Table 4.
Association between continuous variables and buccal mucosa recession
Mucosal height loss (mm) | <0 (n = 37) | 0–0.5 (n = 18) | >0.5 (n = 2) | P-value |
---|---|---|---|---|
Initial mucosa width (mm) | 3.03 ± 1.03 | 2.77 ± 0.99 | 2.32 ± 0.02 | 0.461 |
Initial mucosa height (mm) | 2.11 ± 0.77 | 2.24 ± 0.71 | 2.66 ± 0.25 | 0.531 |
Initial W/H | 1.54 ± 0.48 | 1.25 ± 0.29 | 0.88 ± 0.09 | 0.014* |
Implant buccal inclination angle (deg.) | 2.80 ± 10.15 | 1.19 ± 5.99 | 13.71 ± 0.01 | 0.179 |
Emergence angle (deg.) | 37.94 ± 14.74 | 33.70 ± 11.79 | 39.69 ± 7.38 | 0.540 |
Buccal alveolar bone width (mm) | 1.58 ± 0.82 | 1.45 ± 0.81 | 0.54 ± 0.18 | 0.208 |
*Statistically significant, P<0.05
The association between each variable and buccal VBL is shown in Table 5. Buccal VBL was categorized into three groups:<0, 0–1, and>1 mm. The initial BMW in the group with buccal vertical bone growth was significantly greater than that in the groups with buccal vertical bone loss. The implant buccal inclination angle in the group with buccal vertical bone growth was significantly smaller than that in the groups with buccal vertical bone loss. The BBW in the group with buccal vertical bone growth was significantly greater than that in the groups with buccal vertical bone loss. However, we did not observe a significant difference in the initial mucosa height, initial W/H, and emergence angle among different VBL groups.
Table 5.
Association between continuous variables and buccal vertical bone loss
Vertical bone loss (mm) | <0 (n = 9) | 0–1 (n = 29) | >1 (n = 19) | P-value |
---|---|---|---|---|
Initial mucosa width (mm) | 3.82 ± 1.09 | 2.87 ± 0.76 | 2.58 ± 1.09 | 0.007** |
Initial mucosa height (mm) | 2.62 ± 0.59 | 2.04 ± 0.77 | 2.16 ± 0.71 | 0.120 |
Initial W/H | 1.47 ± 0.32 | 1.53 ± 0.43 | 1.25 ± 0.49 | 0.098 |
Implant buccal inclination angle (deg.) | −4.89 ± 5.30 | 1.68 ± 7.43 | 7.76 ± 9.99 | 0.001** |
Emergence angle (deg.) | 29.19 ± 13.50 | 38.16 ± 15.29 | 37.90 ± 10.20 | 0.205 |
Buccal alveolar bone width (mm) | 2.36 ± 0.74 | 1.56 ± 0.56 | 1.01 ± 0.85 | 0.000** |
**Statistically significant, P<0.01
Correlation analysis
Pearson correlation analysis was further used to determine the effect of each variable on the buccal mucosa level and buccal bone level. The correlation coefficient and P-value for buccal MR and VBL are shown in Table 6. An increased risk of MR was significantly associated with decreased initial BMW (r=−0.381), decreased initial W/H (r=−0.422), and decreased BBW (r=−0.290) (Fig. 4). An increased risk of VBL was significantly associated with decreased initial BMW (r=−0.421), decreased initial W/H (r=−0.305), increased implant buccal inclination angle (r = 0.507), and decreased BBW (r=−0.556) (Fig. 5).
Table 6.
Pearson correlation coefficient for buccal mucosa recession and buccal vertical bone loss
Variables | Buccal mucosa recession | Buccal vertical bone loss | ||
---|---|---|---|---|
r | P-value | r | P-value | |
Initial mucosa width | −0.381 | 0.003** | −0.421 | 0.001** |
Initial mucosa height | 0.029 | 0.828 | −0.141 | 0.295 |
Initial W/H | −0.422 | 0.001** | −0.305 | 0.021* |
Implant buccal inclination angle | 0.103 | 0.445 | 0.507 | 0.000** |
Emergence angle | 0.240 | 0.072 | 0.225 | 0.092 |
Buccal alveolar bone width | −0.290 | 0.028* | −0.556 | 0.000** |
*Statistically significant, P<0.05; **Statistically significant, P<0.01
Fig. 4.
The scatter diagram showing the relationship between buccal mucosa recession and different variables. a The relationship between buccal mucosa recession and BMW. b The relationship between buccal mucosa recession and buccal mucosa W/H. c The relationship between buccal mucosa recession and BBW. Abbreviations: BMW, buccal mucosa width. BBW, buccal bone width. W/H, buccal mucosa width/height ratio
Fig. 5.
The scatter diagram showing the relationship between buccal vertical bone loss and different variables. a The relationship between buccal vertical bone loss and BMW. b The relationship between buccal vertical bone loss and buccal mucosa W/H. c The relationship between buccal vertical bone loss and BBW. d The relationship between buccal vertical bone loss and implant buccal inclination angle. Abbreviations: BMW, buccal mucosa width. BBW, buccal bone width. W/H, buccal mucosa width/height ratio
Discussion
This prospective study investigated the effects of buccal bone width, mucosa height and width, emergence profile, and implant inclination angle on peri-implant hard and soft tissues in the posterior region. To the authors’ knowledge, this is the first detailed study exploring the correlation among buccal alveolar bone, buccal mucosa, and emergence profile.
The posterior mucosa W/H ratio in the present study was stabilized within the range of 1.2–1.4, which is consistent with our previous findings [12]. The W/H ratio at 1 year (1.23 ± 0.38) was significantly lower than that at baseline (1.42 ± 0.38). The decrease in the W/H ratio was mainly attributed to the increase in mucosa height, with the mean value changing from 2.17 mm at baseline to 2.39 mm at 1 year. The reason for this was mainly due to the fact that the patients in this cohort had an average initial BMW of 2.93 mm, which was a thick BMW (≥ 2 mm) with less gingival recession. Therefore, it is reasonable to conclude that increasing the buccal mucosa width increases the tissue height and has better stability over time. In addition, there is a difference in the W/H ratio between this study and previous studies (1.58:1 reported by Nozawa, 1.19:1 reported by Farronato), and this difference may be due to the different tissue adaptation caused by the difference in the implant-abutment connection [11, 21].
The results of the study showed that the level of peri-implant buccal mucosa was influenced by several factors, including initial BMW, initial W/H, and BBW. Specifically, the thinner the mucosa, the smaller the W/H, and the greater the gingival recession. The level of buccal mucosal recession in the present study was − 0.22 ± 0.47 mm. It is noteworthy that buccal gingival margins showed coronal growth when the W/H ratio averaged 1.54 and the initial BMW averaged 3.03 mm, which was consistent with a previous case report [22]. Different methods have been created to assess thick and thin gingival phenotype, including visual assessment, periodontal probe transparency method, ultrasonic method, transgingival probing method [23–25]. It is worth emphasizing that the present study adopted a direct measurement on a digital model, enabling non-invasive and accurate measurement of the actual mucosa width. Besides, the soft tissue surrounding the implant is also influenced by the crown and abutment material. All the cases in this study used titanium abutment and zirconia porcelain crown, which has been proved to have good biocompatibility and mechanical properties [26, 27]. The selection of a consistent material excluded the influence of confounding factors that could lead to different soft tissue responses due to different materials.
Soft tissue topography is determined by the underlying bony structure. The present study showed that the smaller the BBW, the greater the mucosa recession. Specifically, when the initial BBW averaged 0.54 mm, mucosa recession was greater than 0.5 mm at one year. When the initial BBW averaged 1.45 mm and above, mucosa recession was less than 0.5 mm and even showed coronal growth at one year. Consistent with the results of the present study, Farronato’s study showed that the average buccal mucosa recession after three years was 1.22 ± 0.41 mm at BBW values ≤ 0.5 mm [28]. At the same time, BBW can influence vertical resorption of the alveolar ridge, which may, in turn, has an effect on the level of buccal mucosa. Spray et al. investigated the effect of BBW on vertical bone loss, and they found that vertical buccal bone resorption appeared at a BBW of less than 1.8 mm [20]. Similar findings were found in the present study. Results showed that the mean BBW was 2.36 mm in the group with increased vertical bone height, 1.56 mm in the group with bone resorption of 0–1 mm, and 1.01 mm in the group with bone resorption of > 1 mm, the difference of which was statistically significant.
Several studies confirmed the effect of BMW on alveolar bone remodeling in the anterior implant restoration, but there are rare studies in the posterior region [29–31]. The present study revealed the effect of BMW on alveolar bone remodeling in the posterior region. BMW is negatively correlated with buccal vertical bone resorption, the thicker the gingiva, the less buccal bone resorption. Most of the previous studies measured the change of alveolar bone on two-dimensional radiographs, while the present study measured the change of buccal bone height by CBCT, which was more convincing. There was no significant correlation between mucosa height and buccal vertical bone loss, presumably probably because the initial buccal width belonged to thick phenotype in this cohort and the biological alteration was minimal.
The emergence angle of the restorations in the present study was 36.7 ± 13.7 degrees. It is noteworthy that there was no correlation between the emergence angle and buccal vertical bone loss in this range. However, whether a greater emergence angle affects alveolar bone remodeling requires further study. Previous measurements of the emergence angle have mainly been made on periapical radiographs without considering the relationship between the emergence contour and the gingival margin [32–34]. The measurement method used in this study clearly showed the exact point of emergence through the gingival margin in the digital model, and the angle between the tangent line of the restoration at the gingival margin and the implant axis was more clearly depicted. This digital method is characterized by reproducibility and high accuracy compared to conventional measurements.
The present study still has some limitations. Firstly, the sample size of this cohort was small and the observation time was short. The measurement indicators for mucosa and bone are limited to the buccal side, which cannot reflect the 3D dimensional changes of peri-implant tissues. Secondly, this study was the first attempt to measure the digital model superimposed by dentition model and CBCT data together, which would have systematic errors. Methods to reduce the errors will be investigated in the future. Thirdly, it is important to note that these average thresholds may vary depending on tooth position (anterior vs. posterior) and may not be applicable in specific clinical scenarios, including sites exhibiting local inflammation that may directly affect the dimension, morphology, and/or integrity of the peri-implant tissue.
Conclusions
Implant sites in the posterior region presenting a thin BMW, a thin BBW, and a small W/H ratio are more prone to exhibit buccal mucosa recession.
Implant sites in the posterior region presenting a thin BMW, a thin BBW, a small W/H ratio, and a large implant buccal inclination angle are more prone to exhibit buccal vertical bone loss.
Therefore, the authors recommend an initial BMW of at least 2.5 mm and a BBW of at least 1 mm for implants in the posterior region, in order to prevent buccal mucosa recession of more than 0.5 mm and buccal vertical bone loss of more than 1 mm.
Acknowledgements
None.
Authors’ contributions
Y.T.: design, data collection, and original draft preparation. J.W.: methodology and data analysis. L.Q.: reviewing and editing the manuscript. H.Y.: conceptualization, supervision, and funding acquisition.
Funding
This work was supported by grants from Beijing Natural Science Foundation (No. J230032 to H.Y), and the Peking University Medicine Sailing Program for Young Scholars’ Scientific & Technological Innovation (BMU2024YFJHMX010 to Y.T.).
Data availability
All data and materials generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Declarations
Ethics approval and consent to participate
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Peking University Hospital of Stomatology (approval number PKUSSIRB-201840189). This trial was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn) at 25th March, 2019, the number is ChiCTR1900022101. Written informed consent was obtained from individual or guardian participants.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Yiman Tang and Juan Wang contributed equally to this work.
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Data Availability Statement
All data and materials generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.