SCIENTIFIC BACKGROUND AND RATIONALE
Traditionally, implant placement has been based on bone availability, with the
implant industry focused primarily on enhancing implant survival by increasing the
chances of osseointegration. In contrast, the position of the final prosthetic
rehabilitation was considered of secondary importance. In certain instances, this
approach may result in biological, prosthetic, and aesthetic complications. In
contemporary dentistry, evaluating the success of implant therapy transcends the
mere evaluation of implant survival and involves a comprehensive assessment that
takes into consideration the long-term stability of soft and hard peri-implant
tissues, access for oral hygiene, aesthetic demands, occlusal and functional
dynamics, implant loading potential, and minimal invasiveness.
Digital-based planning and guided surgery can maximize the chances of placing
implants in an ideal prosthetic position. Different types of guided surgery have
been described in the literature: (1) Static cast-based partial guidance, which
considers the final prosthetic position without considering bone morphology and in
which bone bed preparation and implant placement are free-handed. (2) Static
computer-based partial guidance, in which the underlying bone morphology is
considered in manufacturing the surgical guide, and that can be used for the
initial, partial, or complete osteotomy, but implant placement is still free-handed.
(3) Static computer-based full guidance that entails the utilization of a pre-made
surgical template, involving both complete osteotomy preparation and implant
placement guided by a prosthetically driven surgical guide; and (4) Dynamic
guidance, that allows real-time guidance during drilling, with the implant position
dynamically displayed on computed tomography data. Dynamic guides are associated
with higher economic costs and pose challenges in in their clinical implementation,
and consequently, static guides are more frequently utilized. The type of support
for the guide can be categorized into three groups: mucosal-supported,
tooth-supported (may be combined with mucosal-supported), or bone-supported.
Implant surgical guides can be produced through two manufacturing processes:
subtractive and additive manufacturing. The subtractive approach involves milling
the surgical guide from a larger polymer block through a computer-numeric controlled
machine. The additive approach is based on 3D printing the guide by sequential
layering. In general, additive processes are more frequently employed, due to
reduced expenses, the production of more guides per printing session, and minimal
waste.
Recent systematic reviews have demonstrated that static fully guided surgery has
higher accuracy to achieve the planned position than free-handed and partially
guided implant placement . Indeed, different RCTs have reported higher chances of
obtaining a prosthetically correct implant position allowing for screw-retained
restorations, lower mean depth deviation, lower angular deviation, as well as
three-dimensional body deviations when using static guidance with respect to
free-handed implants.
However, there is no conclusive evidence on the differences in accuracy when
comparing static guides fabricated either through an additive or a subtractive
process.
STUDY OBJECTIVES The primary aim of this study is to determine whether there are any
differences on the accuracy of implant placement using two different types of static
surgical guides: 3D-printed vs. milled. The null hypothesis is that there will be no
differences in the accuracy of implant placement when comparing 3D-printed and
milled surgical guides.
The primary objective of this investigation will be to evaluate the accuracy of
implant placement defined in terms of differences in precision and trueness (ISO
5725-2) between the planned and the final implant position, when comparing
3D-printed and milled surgical guides.
As secondary objectives the following outcomes will be evaluated: peri-implant
health outcomes (bleeding on probing, suppuration, probing depth), plaque index,
implant survival, implant success, surgery-related outcomes (time, difficulty [VAS
scale], and wound healing index), and patient-reported outcomes measures.
2.1 Clinical relevance A correct implant position is important for the long-term
success of implant therapy. Static computer-assisted implant placement is an
alternative to free-hand surgery that has shown higher accuracy in reaching an
appropriate implant position. However, data on the accuracy associated to the use of
either milled or 3D-printed implant surgical guides is limited.
MATERIALS AND METHODS
3.1. Study design Two-arm, double-blind (examiner, and patient), single-center parallel
randomized controlled trial.
3.2. Trial centers This study will be carried out in the clinic of the Postgraduate of
Specialization in Periodontology and Implant Dentistry at the Complutense University of
Madrid (Spain)
3.4. Intervention / Study Procedures 3.4.1. Screening and Baseline Procedures All
potential study participants will be screened for eligibility according to the inclusion
and exclusion criteria and will be informed about the study procedures.
3.4.2. Informed Consent Written informed consent must be obtained from each patient prior
to performing any study procedure or assessment. Before enrolling a subject, the
Investigator will explain the study protocol, procedures, and objectives to the subject
and/or legal guardian or legally authorized representative. When the subject understands
and is willing to participate in the clinical trial, he/she must sign and date the
IRB-approved Informed Consent Form (ICF). The ICF describes the study and the potential
discomforts, risks, and benefits of participating. One copy of the consent form will be
provided to the subject, and one copy will be maintained with the subject's permanent
medical records. The study site personnel must also enter the date the informed consent
was signed in the subject's source documentation or medical record.
3.4.3. Randomization Each patient will be randomized into the milled or 3D-printed group
according to a balanced distribution system via a computer-generated table of random
numbers. Allocation concealment will be kept during the surgery by means of opaque
envelopes so that the patient is blinded, and it will be kept until the moment of data
analysis by an independent researcher not involved in the execution of the clinical
interventions. Opaque sealed envelopes will be opened at the milling center once the 3D
implant planning has finished, been checked, and sent.
3.4.4. Pre-study phase and guide fabrication Upon inclusion in the study, all potentially
eligible patients (all patients meeting primary inclusion criteria) will receive oral
hygiene instructions (OHI) according to their individual needs. Patients with residual
dentition with signs of periodontitis will also receive periodontal therapy.
After this, all eligible patients will be re-evaluated according to their compliance with
oral hygiene procedures (secondary exclusion criteria) to establish their inclusion in
the trial.
A preoperative intraoral scan of the receptor arch and a cone-beam computed
tomographic scan of the arch of interest will be acquired to digitally plan implant
placement. A blinded investigator with experience in implant dentistry will perform
the virtual planning for all cases based on a prosthetic-driven implant position
using the Medconnect software platform (Archimedes).
The digital planning will consist of 3-dimensional radiographical measurements on
DICOM data to assess the optimal position of the implant(s) based on digital wax-up.
An STL file will be used to construct the surgical guide (S0). At this stage, if
additional bone regeneration procedures are needed to achieve the ideal position of
the implant(s), the surgical planning will be aborted, and other options will be
offered to the patient. Transalveolar sinus floor elevation up to 2 mm will be
allowed. The surgical guide will be designed aiming primarily for tooth support or
mixed (tooth and mucosal) support. Cases where this cannot be achieved will be
excluded.
Once this process has ended, patients will be randomized as described previously to
receive milled guides (anaxCAM PMMA Clear blanks, Anaxdent, Germany) (CORiTEC 150i
PRO miller, Imes-icore®, Germany) or 3D-printed guides (E-Guide resin, EnvisionTEC®,
Germany) (D4K Pro printer, EnvisionTEC®, Germany) performed by the same commercial
manufacturing center (Archimedes, Spain). All guides will be designed with guide
sleeves.
Finally, the guide will be post-processed and sterilized according to the
manufacturer's recommendations.
Before the day of surgery, the surgical guides will be tested for fit and stability
through tactile inspection. In poorly fitted guides, new intraoral and CBCT scans
will be obtained to repeat the digital planning phase.
3.4.5. Surgical procedure
All implant surgeries will be performed under local anesthesia by one of five
calibrated, experienced surgeons who have not been involved in the digital planning
of the implant position.
All implants will be bone-level Klockner Vega® implants (Klockner Implant System,
Spain), ranging from 3.5 to 4.5 mm in diameter and 8 to 12 mm in length.
The selection of performing a flapless or a full thickness mucoperiosteal flap will
be determined before surgery by measuring the availability of keratinized mucosa. A
flapless technique will be selected for cases where at least 2mm of surrounding
keratinized mucosa can be ensured around the whole implant. If performing a flap, a
crestal design will be used to assure that at least 2 mm of keratinized mucosa is
left on the buccal and lingual flaps.
Implant bed preparations and insertions will be done through the 3D surgical guides
following the manufacturer's protocol (Sniper Guide System, Klockner Implant System,
Spain). All implants will be placed 1-1.5 mm subcrestally.
A transmucosal healing abutment and interrupted non-resorbable 5/0 sutures will be
placed.
3.4.6. Postoperative care Patients will be instructed to rinse postoperatively for 1 min
with 0.12% CHX + 0.05% CPC (Perio-aid treatment®) three times a day for 2 weeks. Patients
will also be allowed to take Ibuprofen 600mg every 8 hours as needed. If necessary,
Paracetamol 650mg will be intercalated. Patients will be asked to keep a record of the
medication taken (type of medicine, frequency, and number of days).
Patients will be instructed to refrain from performing regular oral hygiene in the
surgical area immediately after the surgery for one week. Smokers will be asked to limit
(and possibly quit) smoking to no more that 5 cigarettes per day.
Sutures will be removed after 7 days, and self-performed biofilm control in the surgical
area will be reinstituted with the use of a soft toothbrush. At one month, patients will
be instructed to start routine self-performed oral hygiene procedures and will receive
supragingival polishing with an air polishing device (Airflow® EMS) and a subgingival
non-abrasive powder (Erythritol, Plus Powder®, EMS).
Three months after surgery, digital impressions will be taken at the implant level for
single unit restorations or at the abutment level (Permanent) for multiple unit
restorations. If intermediate abutments are used, the day of digital impression will be
screwed and not removed anymore. Titanium bases will be used to cement zirconia CAD-CAM
restorations at the laboratory, which will be then screw at the implant or the abutment
the day of loading. To standardize the prosthetic designs, all the restoration will be
fabricated at the same laboratory (Symmetrya, Oporto). Functional loading will be
considered as the baseline visit for the subsequent follow-up. Professional prophylaxis
and OHI will be performed at 6 and 12 months using ultrasonic and air polishing devices
(Prophylaxis Airflow Master Piezon® EMS) and a subgingival non-abrasive powder
(Erythritol, Plus Powder®, EMS).
3.4.7. Concomitant interventions/medications Locally. Dental or periodontal procedures,
as required by the subject and as deemed necessary by the attending clinician, will be
allowed before and during the trial.
Systemically. All necessary and not delayable concomitant interventions/medications will
be allowed before and during the study. In case of incompatible concomitant systemic
interventions/medications (e.g., bisphosphonates) assessed before the inclusion in the
trial, the patient will not be included (see systemic exclusion criteria). In case the
same treatments have been started after the patient inclusion but before the surgical
treatment, the patient will be excluded from the trial (see "withdrawal criteria"). In
case such treatments have been started after the surgical treatment, the patient will be
retained in the study. Eventually, emergency medical care will always be allowed.
3.6. Statistical analysis
3.6.1. Sample Size Determination of the sample size was based on the mean deviation aft
the implant platform between the static group and the dynamic group reported on previous
studies: Putra et al., 2022, using the mean (SD) of the angular deviation between planned
and implant insertion in G*Power (Version 3.1.9.7 software, Heinrich-Heine University,
Dusseldorf, Germany). The effect size was estimated at 0.914, the significance level was
set at 0,05 and the power at 0.80. The minimum required sample size resulted in 20
patients per group, but will be increased by 20%, expecting any possible dropouts. Thus,
the final sample size will be adjusted to 48 patients, 24 in each group.
3.6.2. Statistical analysis Statistical analyses will be presented both at patient- and
implant-level. Data will be reported as mean and SD unless otherwise specified (e.g., n
[%]). Shapiro-Wilk goodness-of-fit test and histograms will be used to determine the
normal distribution of the quantitative variables. Non-normally distributed variables
will be additionally presented as medians and interquartile range (IQR). All analyses
will be performed using the intention-to-treat population, and the last observation
carried forward approach (LOCF) will be used for missing values.
The primary outcome will be accuracy as a compound parameter, where four different
aspects will be measured: angular deviation, coronal deviation, apical deviation, and
depth deviation. To assess the performance of the intervention, Students' t-test or
Mann-Whitney U tests will be used for quantitative outcomes. Data on categorical outcomes
will be compared using Chi-square test or Fisher-exact test. The secondary outcomes
identified as relevant through the bivariant analysis will be included in a regression
model, considering the accuracy as the primary outcome variable, which will be adjusted
for confounding variables and factors such as the operators experience, type of surgical
stent, etc.
Statistical significance will be set at p<0.05. The analysis will be performed using IBM
SPSS Statistics (version 29.0.1.1, IBM Corporation, New York, NY, USA).