Skip to main content
International Journal of Implant Dentistry
Download PDF

Radiographic and histological evaluation of bone formation induced by rhBMP-2-incorporated biomimetic calcium phosphate material in clinical alveolar sockets preservation

International Journal of Implant Dentistry volume 9, Article number: 37 (2023) Cite this article

Abstract

Purpose

We assessed the efficiency of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated biomimetic calcium phosphate on β-tricalcium phosphate (β-TCP) (rhBMP-2/BioCaP/β-TCP) on bone formation in a model of socket preservation using cone beam computed tomography (CBCT) scanning and histological examination.

Methods

Forty patients undergoing minimally invasive single-root tooth extraction for dental implantation were randomized to three groups according to the material used for socket preservation: filling with rhBMP-2/BioCaP/β-TCP, β-TCP, or natural healing (kept unfilled) (controls). The alveolar sockets (including the control group) were covered by two-layer collagen membranes and sutured. Two CBCT scans were taken, one immediately after socket preservation procedure (baseline) and another 6 weeks later. Gray values (GVs) obtained from CBCT were recorded. During insertion of the dental implant, biopsies were taken and analyzed histologically for new bone formation, residual material, and unmineralized bone tissue at the core of the biopsy.

Results

The mean (± standard deviation) changes of GVs of the CBCT scans at the central area of filled materials were as follows: 373.19 ± 157.16 in the rhBMP-2/BioCaP/β-TCP group, 112.26 ± 197.25 in the β-TCP group, and -257 ± 273.51 in the control group. The decrease of GVs in the rhBMP-2/BioCaP/β-TCP group as compared with the β-TCP group was statistically significant (P < 0.001). Differences in new bone formation (P = 0.006) were also found: 21,18% ± 7.62% in the rhBMP-2/BioCaP/β-TCP group, 13.44% ± 6.03% in the β-TCP group, and 9.49% ± 0.08% in controls. The residual material was10.04% ± 4.57% in the rhBMP-2/BioCaP/β-TCP group vs. 20.60% ± 9.54%) in the β-TCP group (P < 0.001). Differences in unmineralized bone tissue (P < 0.001) were also found (68.78% ± 7.67%, 65.96% ± 12.64%, and 90.38% ± 7.5% in the rhBMP-2/BioCaP/β-TC, β-TCP, and control groups, respectively).

Conclusions

This study shows that rhBMP-2/BioCaP/β-TCP is a promising bone substitute with fast degradation and potent pro-osteogenic capacity that can be useful for socket preservation in implant dentistry.

Trial registration: ChiCTR, ChiCTR2000035263. Registered 5 August 2020, https://www.chictr.org.cn/ChiCTR2000035263.

Graphical Abstract

Introduction

Sufficient alveolar bone is a prerequisite for successful placement of dental implants. However, atrophic maxilla or mandible is a common finding in clinical practice due to tooth loss, trauma, tumors, neoplasm resection, or bone metabolism diseases [1]. To provide adequate alveolar bone for dental implants, socket preservation has been widely used after tooth extraction, and many studies have shown that socket preservation procedures can reduce bone resorption and promote bone formation during the first 3 months after tooth extraction [2, 3].

Different materials, such as autografts, allografts, and xenografts have been used for filling the socket and retaining the alveolar bone volume [4]. Although autografts are considered the gold standard for bone regeneration [5], there are difficulties in obtaining sufficient bone from a single donor site, and the use of various sites involves additional surgery with longer operating and healing times, and increasing discomfort and morbidity [6]. Although using allografts is more feasible, spreading infection diseases is an inconvenience [7, 8] as well as the fact that, in some cultures, allografts and xenografts may be limited for religious reasons.

Synthesized bone substitutes are useful options as they can avoid these aforementioned shortcomings. Different synthesized bone substitute materials have been used in implant dentistry for socket preservation, such as hydroxyapatite (HA), tricalcium phosphate (TCP), biphasic calcium phosphate (BCP) or a combination of these materials. Calcium phosphate (CaP) bioceramics are mostly used as bone substitutes in clinical practice, and low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) (approved by the FDA) [9] added to β-TCP confers osteoinductivity and enhances the performance of this material in bone formation. Although the safety and efficacy of this rhBMP-2/BioCaP/β-TCP combination have been tested both in vitro and in vivo models [10, 11], data on its clinical performance are still limited.

Cone beam computed tomography (CBCT) is widely used in implant dentistry with grey values (GVs) scale to measure density, volume, and contour of bone [12]. However, GVs cannot accurately reflect the bone density when calcium phosphate-based preparations are used as filling materials. In these cases, bone density should be evaluated by histomorphometric techniques.

Therefore, the objective of this study was to determine the efficiency of rhBMP-2/BioCaP/β-TCP in socket preparation using CBCT studies and histological examination of biopsies for assessing bone formation.

Methods

Patient selection and study design

The study was approved by the Clinical Research Ethics Committees of the Academic Center for Dentistry of Amsterdam (code ACTA 202061), Vrije Universiteit Amsterdam, The Netherlands, and Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine (code SH9H-2019-T231-4), China. This trial was conducted following the international standard for clinical investigations with medical devices (ISO 14155:2020). Written informed consent was obtained from all participants.

A total of 40 patients were recruited in this study (15 in rhBMP-2/BioCaP/β-TCP group, 15 in β-TCP group, and 10 in the natural healing group). All patients met the selection criteria shown in Tables 1 and 2. The patients were randomly divided into the following three groups: rhBMP-2/BioCaP/β-TCP, β-TCP, and natural healing (kept unfilled) (controls). After tooth extraction, the socket was filled with either rhBMP-2/BioCaP/β-TCP (particle size 0.25–1 mm, made by Shanghai Rebone Biomaterials Co., Ltd.) or β-TCP (particle size 0.25–1 mm) β-TCP group, while the natural healing group was not filled with any CaP material. Two layers of collagen membrane (Geistlich Bio-Gide® bilayer collagen membrane, 25 × 25 mm) were used to cover the filling materials in the alveolar sockets of all patients. The soft tissue was sutured. Immediately after surgery, the first CBCT scan was taken and the GVs were recorded. Six weeks after the procedure, a second CBCT scan was obtained before placement of the implant. In addition, a biopsy of 2.3 mm in diameter and 6 mm height was taken using a trephine drill (3 and 2 mm, outer and inner diameters, respectively) at the same point of the implant insertion (Figs. 1, 2). The operation was completed when the implant was inserted and the sutures were removed after 2 weeks.

Table 1 Inclusion criteria
Full size table
Table 2 Exclusion criteria
Full size table
Fig. 1
figure 1

Schematic of clinical trial procedure. A The patients were randomly divided into rhBMP-2/BioCaP/β-TCP, β-TCP, and natural healing groups; B tooth extraction, C the tooth socket filled with either rhBMP-2/BioCaP/β-TCP or β-TCP in relative groups, D the first layer of collagen membrane covered the alveolar sockets and 2-3 mm over the socket edge), E the second collagen membranes, F sutured, G 2 weeks later, took out the suture, H after 6 weeks, soft tissue flap releasing, I a trephine drill (outer diameter 3 mm, inter 2.3 mm diameter) is used to obtain the biopsy, J collected biopsy (2.3 mm in diameter × 6 mm in height)

Full size image
Fig. 2
figure 2

Intra-oral photographs of socket preservation and dental implant surgery. A The upper left first premolar needed to be removed. B The gingival biotype was a thick tissue biotype. C Tooth extraction. D The tooth socket was filled with rhBMP-2/BioCaP/β-TCP. E Two layers of collagen membrane covered the alveolar socket. F Sutured. G 6 weeks later. H Soft tissue flap releasing. I Obtained the biopsy and inserted an implant. J, K Guided bone regeneration (GBR) for the horizontal bone gain. L Sutured

Full size image

Radiographic measurement

The CBCT images were collected using the Planmeca 3D Imaging System (field-of-view of 8 cm (D) × 8 cm (H), resolution 0.16 mm, Planmeca, Finland). After being exported as digital imaging and communications in medicine (DICOM) files, the data were analyzed using planning software (Nobel Clinician, Nobel Biocare, Sweden) for GV measurement (Fig. 3). Three-dimensional images focused on the socket site to identify the central point of the pulp cavity at the enamel–cementum junction of the mesial and distal adjacent teeth were obtained. The connection of the two points helps to determine the coronal plane (Fig. 4A). The horizontal reference line was taken through the highest alveolar ridge of extraction fossae (crest of the alveolar ridge) (Fig. 4B). The buccal-lingual section followed the center line of the root of the tooth. Then the tooth-long axis was followed to identify the 3 mm point (GV measurement point) from the baseline, and the GV was measured based on the software function (Fig. 4C). A 3D model showed the 3D information (Fig. 4D), and the schematic diagram of the GV point is shown in Fig. 5. All measurements were performed by three independent investigators, and the GV change was calculated as the difference between baseline (GV1) and final GV obtained at 6 weeks after material filling (GV change = GV1 – GV2).

Fig. 3
figure 3

Data import. A Panoramic tomography. B Buccal-lingual section of the surgery area. C 3D model

Full size image
Fig. 4
figure 4

The measurement point of GV. A Look for the central point of the pulp cavity at the enamel-cementum junction of the mesial and distal adjacent teeth. The connection of the two points helps determine the coronal plane. B The horizontal reference line was taken through the highest alveolar ridge of extraction fossae (crest of the alveolar ridge). C The buccal-lingual section followed the center line of the root of the tooth. Then the tooth-long axis was followed to find the 3 mm point (GV measurement point) from the baseline and measured the GV based on the software function. D 3D view

Full size image
Fig. 5
figure 5

Schematic diagram of the identification of measurement point for GV. The GV measurement baseline is on the alveolar ridge’s crest. Following the long axis of the tooth, the red dot is a point for measuring bone density underneath 3 mm of baseline. The center part of the biopsy is the same as the GV-measured point of the CBCT image

Full size image

Histomorphological examination

Tissue biopsies were immersed in 10% neutral formalin solution for 24 h with the trephines.

Thereafter, samples were dehydrated with alcohol gradients after flushing, and embedded with polymethyl methacrylate. The samples were sectioned opposite to the long axis of the biopsy, and five tissue sections of 600 µm thicknesses (1 mm spacing) were collected for each piece, polished to a final thickness of 50–100 µm, and stained with McNeal’s tetrachrome staining. The Image Pro Plus program (version 6.0, Media Cybernetics) was used to calculate the area of new bone, the residual material, and the unmineralized tissue at the center slice of the biopsy (Fig. 6) The center part of the biopsy as the same as the GV-measured point of the CBCT image area was measured. Measurements were performed by three independent pathologists, and the mean value of these measurements was considered.

Fig. 6
figure 6

Light micrographs of biopsy slice (diameter 1.1 mm) in the natural healing group (A), rhBMP-2/BioCaP/β-TCPgroup (B), and β-TCP group (C) 6 weeks after implantation. Stained with McNeil’s Tetra chrome basic fuchsine and toluidine blue O. a Residual material, b new bone, c unmineralized tissue

Full size image

Statistical analysis

Categorical data are expressed as frequencies and percentages, and continuous data as mean (± standard deviation, SD) or median and interquartile range (IQR) (25th–75th percentile). Analysis was performed in the per-protocol (PP) dataset, that is, all patients who were randomized, received the intervention, and completed the study procedures. A single-factor analysis of variance (ANOVA) was used to compare CVs changes among the three study groups. The Mann–Whitney U test was used to compare the area of residual material between rhBMP-2/BioCaP/β-TCP and β-TCP groups, and the Kruskal–Wallis test for the comparison of the new bone area and unmineralized tissue area among the three study groups. Interrater reliability was assessed with the Cronbach’s alpha (α) coefficient. Statistical significance was set at P ≤ 0.05. The IBM Statistical Package for the Social Sciences software (SPSS) (version 23.0) was used for the analysis of data.

Results

Of the 40 patients recruited for the study, 4 (10%) were excluded due to protocol violations (prohibited medication history, significantly exceeding the follow-up time-point limit, and severely defective bone), 2 of them from the natural healing group, and 1 patient each from the rhBMP-2/BioCaP/β-TCP and β-TCP groups, respectively. Therefore, the study population included 14 patients in the rhBMP-2/BioCaP/β-TCP group, 14 in the β-TCP, and 8 in the control group.

GV changes on CBCT images

In the first CBCT scan (baseline), there were no statistically significant differences in GVs between the rhBMP-2/BioCaP/β-TCP and β-TCP groups (Table 3). After 6 weeks of socket preparation, the GV change at the 3 mm point below the socket ridge showed significant statistical differences among the three groups (Table 4), and GV changes in the rhBMP-2/BioCaP/β-TCP group were significantly greater than in the β-TCP group (373.19 ± 157.16 vs.112.26 ± 197.25). The median GV (min, max) of the rhBMP-2/BioCaP/β-TCP group was 386.67 (157.33, 642.67) as compared with 67.67 (− 198, 443) in the β-TCP group (Table 5).

Table 3 Initial GV in β-TCP and rhBMP-2/BioCaP/β-TCP group
Full size table
Table 4 Comparison of CBCT data of the GV change in three groups
Full size table
Table 5 Comparison of CBCT data of the GV change in β-TCP group and RhBMP-2/BioCaP/β-TCPgroup
Full size table

Histomorphological results

The percentage of new bone area at the 3 mm point was statistically significant different in the three study groups, with higher values in the rhBMP-2/BioCaP/β-TCP group (21.18% ± 7.62% in the rhBMP-2/BioCaP/β-TCP group, 13.44% ± 6.03% in the β-TCP group, and 9.49% ± 0.08% in controls). Also, the median (min, max) values were 20.93% (10.62%, 39.08%) in the rhBMP-2/BioCaP/β-TCP group, 13.48% (3.78%, 23.42%) in the β-TCP group, and 12.21% (0.28%, 18.58%) in the controls (Table 6). A comparison of the percentages of new bona areas showed statistically significant differences between the rhBMP-2/BioCaP/β-TCP group and the remaining two groups, but significant differences between the β-TCP and control groups were not found (Table 7).

Table 6 Comparison of histological data of the biopsies-PPS in three groups
Full size table
Table 7 Pairwise comparison of histological data of the new bone area %
Full size table

In the rhBMP-2/BioCaP/β-TCP group, the percentage of residual materials area was 10.04% ± 4.57%, the median (min, max) was 10.47% (2.58%, 16.80%), which was significantly lower than that observed in the β-TCP group, 20.60% ± 9.54%, median (min, max) was 18.24% (9.38%, 42.22%) (Table 6).

There were statistically significant differences in the percentage of unmineralized tissue area among the three groups (the rhBMP-2/BioCaP/β-TCP group: 68.78% ± 7.67%; the β-TCP group: 65.96% ± 12.64%; and the natural healing group: 90.38% ± 7.5%) (P < 0.001) (Table 6). Comparing within groups, the percentage of unmineralized tissue area in both the rhBMP-2/BioCaP/β-TCP group and the β-TCP groups were significantly lower than in controls, but there was no statistically significant differences between the 2/BioCaP/β-TCP and the β-TCP groups (Table 8).

Table 8 Pairwise comparison of histological data of the unmineralized tissue area %
Full size table

Discussion

This study used CBCT scanning and histological examination to evaluate degradation and new bone formation associated with the use of rhBMP-2/BioCaP/β-TCP and β-TCP as filling materials in socket preservation. CBCT scanning showed that there was a greater GV decrease in the rhBMP 2/BioCaP/β-TCP group than in the β-TCP group, which suggest a faster degradation rate of this material. In addition, less residual material and more new bone formation were identified in rhBMP-2/BioCaP/β-TCP group based on histomorphometric examination.

In both CBCT and biopsy tissue samples, the center of the filled area was selected to assess bone density, the volume of residual material, and new bone, as there were fewer interference factors (soft tissue and old bone tissue) around the target sites. Since the biopsies were 6 mm high, 3 mm under the reference of the alveolar ridge and alongside the tooth-long axis was included for GV change measurement, and CBCT results revealed that rhBMP-2/BioCaP/β-TCP group has more GV decrease in CBCT images, which indicated faster degradation than β-TCP group, and this assumption was confirmed in histomorphometric evaluations. Despite the CBCT results were consistent with those from histomorphometric assays. GV from CBCT alone cannot precisely reflect bone density, as GV quantifies the amount of X-ray attenuation of bone tissue and filled materials. Therefore, CBCT cannot independently determine the occurrence of new bone development.

The faster degradation of rhBMP-2/BioCaP/β-TCP may be attributed to more cell adhesion. In biomaterial-induced bone regeneration, biomaterials act as scaffolds where bone cells and osteoclasts can adhere and grow [13, 14]. The osteoclast-induced degradation of biomaterials has been extensively reported [15]. Although pore size, porosity, and the roughness of rhBMP-2/BioCaP/β-TCP may benefit cell adhesion including osteoclasts adhesion, further studies are needed to assess these characteristics of rhBMP-2/BioCaP/β-TCP.

Multislice computed tomography (MSCT) and micro-CT have been widely used to evaluate bone density, using the Hounsfield unit (HU) values, in orthopedics and laboratory studies [16]. However, they are not popular in dental clinical practice. Alternatively, CBCT is prevailing in evaluating the contour of alveolar bone before implant surgery, due to lower radiation, simpler design, and acceptable image resolution [17]. Some researchers compared HU from MSCT with GV from CBCT and concluded that the GV was more reliable for detecting and analyzing hypodense structures [18]. For bone evaluations, it was reported that high-resolution CBCT could be used for imaging quantitative bone morphometry assessment [19] and suggested there is a positive correlation between the GVs and the HUs values in quantifying bone tissue [20]. Similarly, it was reported that CBCT was as accurate and reliable as MSCT in predicting bone density and assessing changes in bone density around dental implants [21]. In 2013, radiographic bone density obtained from CBCT was compared with bone volumetric/total volume from micro-CT, and the result showed that it has a strong positive correlation with these two measurements. This study concluded that CBCT is a dependable tool for evaluating bone density preoperatively [22]. We here explored the potential application of CBCT in bone density evaluation in socket preservation. The results also implied CBCT is a potential tool to analyze the degradation of bone substitutes. However, the surgery of obtaining the biopsy was done by free hand, so the measurement points of the two methods cannot be guaranteed to coincide exactly. Next step, we will use the digital design and digital surgery guide technology to improve the consistency of the measurement positions of the two methods.

Alveolar ridge preservation can provide adequate alveolar bone for dental implants [23,24,25,26].

In this study, patients with extraction defect assessment (EDS) class 1 (EDS-1) or 2 (EDS-2), having less bone loss than those with EDS-3 or EDS-4, were included after tooth extraction, and they were in a better condition for bone healing. The rhBMP-2/BioCaP/β-TCP group was superior to β-TCP and natural healing (control) groups in bone formation. However, to assess the efficiency of rhBMP-2/BioCaP/β-TCP in adverse conditions for bone regeneration (e.g., EDS-3 and EDS-4), more studies are warranted.

Conclusion

rhBMP-2/BioCaP/β-TCP is a promising bone substitute with fast degradation and potent pro-osteogenic capacity and can be used for socket preservation in implant dentistry. In addition, CBCT is a valuable technique to evaluate the degradation of filled bone substitutes in clinical practice.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

References

  1. Titsinides S, Agrogiannis G, Karatzas T. Bone grafting materials in dentoalveolar reconstruction: a comprehensive review. Jpn Dent Sci Rev. 2019;55(1):26–32. https://doi.org/10.1016/j.jdsr.2018.09.003.

    Article  PubMed  Google Scholar 

  2. Avila-Ortiz G, Elangovan S, Kramer KW, Blanchette D, Dawson DV. Effect of alveolar ridge preservation after tooth extraction: a systematic review and meta-analysis. J Dent Res. 2014;93(10):950–8.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fee L. Socket preservation. Br Dent J. 2017;222(8):579–82.

    Article  PubMed  Google Scholar 

  4. Jamjoom A, Cohen RE. Grafts for ridge preservation. J Funct Biomater. 2015;6(3):833–48.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yunus Basha R, Sampath Kumar TS, Doble M. Design of biocomposite materials for bone tissue regeneration. Mater Sci Eng C Mater Biol Appl. 2015;57:452–63.

    Article  PubMed  Google Scholar 

  6. Kloss FR, Offermanns V, Kloss-Brandstätter A. Comparison of allogeneic and autogenous bone grafts for augmentation of alveolar ridge defects-A 12-month retrospective radiographic evaluation. Clin Oral Implants Res. 2018;29(11):1163–75.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Buck BE, Malinin TI, Brown MD. Bone transplantation and human immunodeficiency virus An estimate of risk of acquired immunodeficiency syndrome (AIDS). Clin Orthop Relat Res. 1989;240:129–36.

    Article  Google Scholar 

  8. Zamborsky R, Svec A, Bohac M, Kilian M, Kokavec M. Infection in bone allograft transplants. Exp Clin Transplant. 2016;14(5):484–90.

    PubMed  Google Scholar 

  9. Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med. 2008;2(2–3):81–96.

    Article  PubMed  Google Scholar 

  10. Zheng Y, Wu G, Liu T, Liu Y, Wismeijer D, Liu Y. A novel BMP2-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particle: a biodegradable and highly efficient osteoinducer. Clin Implant Dent Relat Res. 2014;16(5):643–54.

    Article  PubMed  Google Scholar 

  11. Liu Y, Schouten C, Boerman O, Wu G, Jansen JA, Hunziker EB. The kinetics and mechanism of bone morphogenetic protein 2 release from calcium phosphate-based implant-coatings. J Biomed Mater Res A. 2018;106(9):2363–71.

    Article  PubMed  Google Scholar 

  12. Mah P, Reeves TE, McDavid WD. Deriving Hounsfield units using grey levels in cone beam computed tomography. Dentomaxillofac Radiol. 2010;39(6):323–35.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jenkins TL, Little D. Synthetic scaffolds for musculoskeletal tissue engineering: cellular responses to fiber parameters. NPJ Regen Med. 2019;4:15. https://doi.org/10.1038/s41536-019-0076-5.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Collins MN, Ren G, Young K, Pina S, Reis RL, Oliveira JM. Scaffold fabrication technologies and structure/function properties in bone tissue engineering. Adv Func Mater. 2021. https://doi.org/10.1002/adfm.202010609.

    Article  Google Scholar 

  15. Gao C, Peng S, Feng P, Shuai C. Bone biomaterials and interactions with stem cells. Bone Res. 2017;5:17059. https://doi.org/10.1038/boneres.2017.59.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Buenger F, Eckardt N, Sakr Y, Senft C, Schwarz F. Correlation of bone density values of quantitative computed tomography and hounsfield units measured in native computed tomography in 902 vertebral bodies. World Neurosurg. 2021;151:e599–606.

    Article  PubMed  Google Scholar 

  17. Jacobs R, Salmon B, Codari M, Hassan B, Bornstein MM. Cone beam computed tomography in implant dentistry: recommendations for clinical use. BMC Oral Health. 2018;18(1):88. https://doi.org/10.1186/s12903-018-0523-5.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Patrick S, Birur NP, Gurushanth K, Raghavan AS, Gurudath S. Comparison of gray values of cone-beam computed tomography with hounsfield units of multislice computed tomography: an in vitro study. Indian J Dent Res. 2017;28(1):66–70.

    Article  PubMed  Google Scholar 

  19. Tayman MA, Kamburoğlu K, Ocak M, Özen D. Effect of different voxel sizes on the accuracy of CBCT measurements of trabecular bone microstructure: a comparative micro-CT study. Imaging Sci Dent. 2022;52(2):171–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Selvaraj A, Jain RK, Nagi R, Balasubramaniam A. Correlation between gray values of cone-beam computed tomograms and Hounsfield units of computed tomograms: a systematic review and meta-analysis. Imaging Sci Dent. 2022;52(2):133–40.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lee SH, Yun PY, Yi YJ, Kim YK, Lee HJ, Jo DW. Low bone density predictability of CBCT and its relation to primary stability of tapered implant design: a pilot study. J Oral Implantol. 2022. https://doi.org/10.1563/aaid-joi-D-21-00159.

    Article  PubMed  Google Scholar 

  22. González-García R, Monje F. The reliability of cone-beam computed tomography to assess bone density at dental implant recipient sites: a histomorphometric analysis by micro-CT. Clin Oral Implants Res. 2013;24(8):871–9.

    Article  PubMed  Google Scholar 

  23. Roberto C, Paolo T, Giovanni C, Ugo C, Bruno B, Giovanni-Battista M-F. Bone remodeling around implants placed after socket preservation: a 10-year retrospective radiological study. Int J Implant Dent. 2021. https://doi.org/10.1186/s40729-021-00354-7.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Meijndert CM, Raghoebar GM, Vissink A, Meijer HJA. Alveolar ridge preservation in defect sockets in the maxillary aesthetic zone followed by single-tooth bone level tapered implants with immediate provisionalization: a 1-year prospective case series. Int J Implant Dent. 2021;7(1):18. https://doi.org/10.1186/s40729-021-00292-4.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Papace C, Büsch C, Ristow O, Keweloh M, Hoffmann J, Mertens C. The effect of different soft-tissue management techniques for alveolar ridge preservation: a randomized controlled clinical trial. Int J Implant Dent. 2021;7(1):113. https://doi.org/10.1186/s40729-021-00390-3.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lee J, Yun J, Kim J-J, Koo K-T, Seol Y-J, Lee Y-M. Retrospective study of alveolar ridge preservation compared with no alveolar ridge preservation in periodontally compromised extraction sockets. Int J Implant Dent. 2021;7(1):23. https://doi.org/10.1186/s40729-021-00305-2.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Caplanis N, Lozada JL, Kan JY. Extraction defect assessment, classification, and management. J Calif Dent Assoc. 2005;33(11):853–63.

    PubMed  Google Scholar 

  28. Hwang D, Wang HL. Medical contraindications to implant therapy: part I: absolute contraindications. Implant Dent. 2006;15(4):353–60.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Frederieke Monchen and Isa Massee for collecting CBCT data, Dr. Naichuan Su for statistical data analysis, and Marta Pulido, MD, for editing the manuscript.

Funding

This work was supported by the NWO grant (No. 729001041) and the Dutch ZonMW grant LSH2TREAT (No. 436001004).

Author information

Authors and Affiliations

  1. Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands

    Yuanyuan Sun, Chunfeng Xu, Mingjie Wang, Lingfei Wei & Yuelian Liu

  2. Department of Second Dental Center, Shanghai Ninth People’s Hospital, School of Medicine, College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China

    Yuanyuan Sun, Lingfei Wei & Yiqun Wu

  3. Department of Oral Implantology, Yantai Stomatological Hospital, Binzhou Medical University, Yantai, China

    Lingfei Wei

  4. Profess Medical Consultancy BV, Heerhugowaard, The Netherlands

    Herman Pieterse

Authors
  1. Yuanyuan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunfeng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mingjie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lingfei Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Herman Pieterse
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yiqun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuelian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YS: writing—original draft and visualization; CX and MW: writing—review and editing; HP: performed in trial design and management; YW and LW: writing—review; YL: conceptualization; supervision; writing—review and editing.

Corresponding author

Correspondence to Yuelian Liu.

Ethics declarations

Ethical approval and consent to participate

The study was approved by the Clinical Research Ethics Committees of the Academic Center for Dentistry Amsterdam (code ACTA 202061), Vrije Universiteit Amsterdam, the Netherlands and Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine (code SH9H-2019-T231-4), China.

Consent for publication

Written informed consent was obtained from all participants.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Y., Xu, C., Wang, M. et al. Radiographic and histological evaluation of bone formation induced by rhBMP-2-incorporated biomimetic calcium phosphate material in clinical alveolar sockets preservation. Int J Implant Dent 9, 37 (2023). https://doi.org/10.1186/s40729-023-00491-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40729-023-00491-1

Keywords