Primary stability and PES/WES evaluation for immediate implants in the aesthetic zone: a pilot clinical double-blind randomized study

The use of immediate implants in the aesthetic area is a technique widely used in modern implantology. The characteristics of the patient, the implant, and the surgical procedure used may influence the final results. The aim was to assess whether the implant design affects primary (P.S.) and secondary stability (S.S.), bone level (B.L.), and PES/WES evaluation. Twenty implants with two different designs (n = 10) were immediately placed and randomly located in the upper anterior maxilla with no grafting material. Implant-Stability-Quotient (ISQ), B.L., and Pink-Esthetic-Score/White-Esthetic-Score (PES/WES) were evaluated. Shapiro–Wilk normality test was performed to determine the sample normality, as the data did not follow a normal distribution, the Wilcoxon-Mann–Whitney test was applied (p < 0.05). ISQ was determined at placement (PS): control 59.1 (C.I.54.8–63.3); experimental 62.2(C.I.60.1–64.2) and three months after placement (SS): control 62.2.1 (C.I.53.3–71.0); experimental 67.2(C.I.65.8–68.5). The BL was measured at three months after placement: control 0.38 mm (C.I.− 0.06 to  + 0.83); experimental 0.76 mm (C.I.0.33–1.19) and at 12 months post-loading: control 0.07 mm (C.I.− 0.50–0.65); experimental 0.90 mm (C.I.0.38–1.42). PES/WES values were evaluated for the control group: 15 (C.I.12.68–17.32), and for the experimental group 15.20 (C.I.11.99–18.41). No significant differences were shown between both implant designs. A good grade of osseointegration and primary/secondary stability was achieved, as well as proper maintenance of crestal bone and adequate PES/WES scores. The criteria for selection for the ideal patient for immediate implant placement is essential. ClinicalTrials Protocol ID: NCT04343833.

The objective of this study was to determine whether a new macro-and micro-geometric design en boasted better primary stability and better aesthetic results in immediate implants placed in the aesthetic zone when compared to a conventional design implant.

Materials and methods
Sample. Sample description. A total of 20 patients, distributed in two groups with ten patient each (experimental and control) were included in this study. All patients signed a double informed consent, one for implant placement and one for their participation in the study. The study follows the Declaration of Helsinki recommendations 19 . The Ethics Committee of the University of Murcia approved the study protocol with ID: 2076/2018, and was registered at ClinicalTrials with ID: NCT04343833 on 13/04/2020. All patients were treated in the Dental School, University of Murcia, as they requested for treatment from 02/10/2017 to 19/09/2019. The preselection was performed by a dentist who was unaware of the subsequent allocation to the treatment groups (AINS).
Inclusion criteria. All patients were older than 18 years old who present a vertical fracture in an upper incisor that can not be treated conservatively and ended in the extraction, and the treatment needed is a unitary implant. Both males and females were included in the sample. Good systemic health status (ASA I or II), an oral hygiene index of < 2 (Löe and Silness), a minimum of 2 mm of attached mucosa, a minimum of 8 mm of vertical bone, and a minimum of 7 mm of bucco-lingual bone.
Exclusion criteria. Traumatic or complicated incisor extraction, pregnant or women in the lactation period, the use of any medication that contraindicates implant treatment, a history of alcohol or drug abuse, a requirement for guided bone regeneration procedures or soft tissues augmentation procedures, and failure to comply with the study protocol.
Implants. All implants were developed by the same manufacturer and were approved by the regulations of the European Certificate. The traceability was guaranteed by Q.R. Genetic Codes® (Ticare, Mozo Grau, Valladolid, Spain).
In the control group (Group A), patients were treated with conventional implants Inhex Ticare Standard (Mozo Grau, Ticare, Valladolid, Spain). The implants presented a surface treated with Reabsorbable Blast Media (RBM), conical macro-design with non-aggressive threads, internal connection, and platform switching. On the implant shoulder, the beveled design of the platform was characterized by a rounded shape of 45°.
In the experimental group (Group B), patients were treated with Implants Inhex Quattro Ticare (Mozo Grau, Ticare, Valladolid, Spain). The implants also presented a surface treated with RBM, conical macro-design with expanded micro threads, internal connection, and platform switching. The implant shoulder showed the same beveled design than group A (Fig. 1).

Study Protocol
A total of 20 patients were randomly distributed into two groups (Fig. 2) following the randomization application https:// www. random. org/ seque nces/: • Group A (control) (n = 10) (Inhex Ticare Standard, Mozo Grau, Ticare, Valladolid, Spain) • Group B (experimental) (n = 10) (Inhex Quattro Ticare, Mozo Grau, Ticare, Valladolid, Spain) The distribution was kept in a numbered envelope until the time of the intervention. Each patient was numbered consecutively, as admitted in the study, and the corresponding envelope opened at the time of surgery.
All patients were treated by the same surgeon (ASP), who was informed of the assigned group just before surgery. At the time of operation, the tooth was atraumatically extracted, and the implant was immediately placed following the surgical protocol recommended by the manufacturer. A temporary prosthesis was made without occlusal contact. The protocol followed by all patients is schematized in Fig. 3.
Patients were followed-up at one-week, one-month, two-months, and three-months post-surgery. Once the osseointegration process was reached, the implant was loaded with the definitive prosthesis, and the patient was monitored every three months until one-year post-loading, assuming a total follow-up time of 15 months. Controls were performed at the University Dental Clinic Of the University of Murcia. The data were stored on a spreadsheet and kept anonymous.    Parameters evaluated by WES. The WES focuses specifically on the visible part of the restoration and in base on the following five parameters: (1) tooth form, (2) tooth volume/outline, (3) color (hue and value), (4) Surface texture, and (5) translucency ( Fig. 4). Each parameter is evaluated by comparison with the adjacent teeth, giving a value ranged from 0 to 2. A total score of 10 can be obtained, considering acceptable from 6 21 . Therefore, in the PES/WES evaluation, a maximum score of 20 can be achieved and represents the optimal state for both soft and hard tissues of the rehabilitated teeth compared with the adjacent teeth. The minimum acceptable PES/WES score is set to 12 21 . (Table 1).
Bone level (B.L.). The bone level (B.L.) was determined by an intraoral digital radiograph taken parallel to the long axis of the implant, and it was expressed as the mean between the mesial and the distal B.L. To determine the B.L. values, all implants were inserted, leaving the implant neck just at the level of the remaining alveolar bone. After the healing process (three months), and once the prosthesis was inserted, a standardized radiograph was taken using a custom bite block. The distance from the implant neck to the first contact between the bone and the implant was determined. It was measured in both sides, mesial and distal, and the mean between both values was established as the B.L. value. The digital x-ray images were processed and measured with Gesimag Software (Medical Informatics, Barcelona, Spain). At 12-months post-loading, a new B.L. value was measured with the bite block preserved ( Table 2).
Operator calibration. The same calibrated single operator measured all the photographs (SMG). All the records were numbered and were randomly reevaluated without prior knowledge of the operator so that the reliability index could be calculated. The intraclass correlation coefficient (ICC) was calculated to consider operator calibration. A value equal or higher of 0.8 was regarded as reliable ICC, being the value 1 equivalent to 100% agreement and the value 0 equivalent to 0% agreement between the different measurements.     (Table 3). Fourteen implants were placed in upper central incisors and six implants in upper lateral incisors. No adverse events were observed during the course of the study. There was one failure in the control group at six months due to mobility in a 50 years old woman, although without inflammation or pain. This implant was removed, and the patient dropout the study. All teeth had a previous canal root treatment with no active apical focus and were extracted due to unrecoverable crown fracture.  (Fig. 6). There were no statistically significant differences (p = 0.165) ( Table 4).  (Fig. 6). There were no significant differences (p = 0.035) ( Table 4).

Discussion
After the publication of the first pioneer studies in the field of immediate implantology, some publications have appeared showing a particular interest [22][23][24] . In these studies, the authors concluded that the placement of immediate implants does not prevent crestal bone reabsorption both vertically and horizontally. Our results yield the same conclusions, as in most cases, there was a loss of bone level.
Many researchers have tried to determine the success rate of immediate implants related to delayed implants, which have been considered the gold standard. Del Fabro et al. showed a survival rate of 95% for immediate implants, comparable to the delayed implants 25 . In our study, we had one implant failed at six months in the control group, presenting a success rate of 95%, being this data in agreement with the referred author.
In our study, only those patients with grade 1 in the classification of Ellian et al. were selected 26 . Among these pre-selected patients, those patients who also had a rating 1, 2, or 3 in the Kan's classification 27 were selected.  www.nature.com/scientificreports/ These strict choice criteria made our study candidates very favorable. This rigorous selection meant that only 10% of the candidates were selected to participate. We strongly believe that this selection has been part of the success and high stability achieved, but at the same time, it limits the extrapolation of the results to the whole population. We determined the three-dimensional position of the implant by the prosthetically guided planning, and the results were also improved by the use of the platform switching and the placement of the implants at bone level 28 .
We did not use any bone or soft tissue graft, only patients with a thick phenotype were selected. To determine the patient´s suitability, we relieve the transparency criteria of the periodontal probe 29 . This selection involved an adequate width and height of the keratinized mucosa.
As for bone grafting, when we place immediate implants, it is generally accepted that the space between the vestibular cortical and the implant (GAP) exceeding two mm should be grafted with bone substitutes 30 , but not all authors agree with this statement 31,32 , being one of the topics without conclusive results at present 16,17 . In our study, we decided not to perform any bone graft in the GAP regardless of the distance between the vestibular cortical and the implant.  Both implant designs achieved satisfactory clinical results. Only one control group implant was lost, which is generally within expectations. It should be noted that the exhaustive selection of patients created the appropriate clinical framework for these results. This is evident from the absence of statistically significant differences between the two implant designs. However, we believe that these results could have favored the experimental group in clinical situations with low-density bone or alveoli type 2, because the new implant of the experimental group has a different thread design that exert more significant pressure on the cortical, favoring the appearance of small bone resorption that, however, does not affect the aesthetic score in the present study.
It must be noted that the implant surface design (outer shapes and thread pitches) influence directly in the resonance frequency values, as well as the implant shape, being tapered implants the most sensitives to bone maturation levels 33 .
One of the limitations to keep in mind is that there are authors who claim that one single value, such as the ISQ, is not suitable to state the level of osseointegration since it is the result of several factors such as cortical bone thickness, trabecular bone properties or bone to implant contact area 34 .
As for secondary stability (at three months after implant placement), the excellent response of RBM surfaces is already known. We did not expect to find differences as it occurred. Once osseointegration has been achieved, the similarities of the intrinsic characteristics of both implants are probably not a significant difference in BIC values, as demonstrated in animal studies 35 .Regarding BL values, both systems have managed to maintain the alveolar bone without the use of graft materials. It shows some interest that three implants had bone levels that had exceeded the implant shoulder at three months (two controls and one experimental). In the twelve-months follow-up, we also did not find significant differences between the two implant designs, and six implants showed bone formation above the implant shoulder (five controls and one experimental).
The PES/WES values for both systems resulted in adequate aesthetic indexes, without significant differences. All values improved with the time progression except for the vestibular contour. Our results indicate a gradual collapse of the gingival contour with no repercussions as to the other variables of the PES. Both the papillae, the margin, the color and texture of the soft tissue improved over time. These findings could provide indirect evidence in favor of grafting with bone substitutes in the GAP when an immediate implant is placed. The WES index remained unchanged as expected throughout the follow-up period.
Our study possesses some limitations, such as those already described regarding exquisite patient selection and the inclusion and exclusion criteria. Due to the small sample size and power, we present this study as a pilot clinical double-blind randomized study. A higher sample size would be desirable for future research. Thus, we only present the results of a twelve-months follow-up after loading, and we offer only clinical evaluation but not histological determination since the study was done in vivo and humans. But the study also has some strengths such as the randomized distribution of the sample, the blind evaluation, the management in a controlled environment, and the non-use of bone graft or soft tissue graft in any patient, which could disturb the results. There was no external source of financing, and none of the authors received any financial or material retribution. Our results could be of particular interest to the clinic that handles this clinical situation day by day. The clinical relevance of this study is that the diagnosis and proper treatment planning must be made to choose the right patient for immediate implants to achieve the best clinical results.

Conclusions
Within the limitations of this study, we can conclude that: • Both implant designs can induce osseointegration under immediate placement. • Both implant designs offer an acceptable value of ISQ for primary and secondary stability.
• Proper stable radiographic crestal bone levels are maintained in both systems at 12-months follow-up.
• Both systems showed similar PES/WES values. • The difference in design for both implant systems does not affect primary/secondary stability, bone level, or PES/WES value when the patient is appropriately selected for immediate implant placement. www.nature.com/scientificreports/ 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:// creat iveco mmons. org/ licen ses/ by/4. 0/.