Clinical trial NCT04480073: Guided Bone Regeneration With Customized Titanium Meshes
Official title: Customized CAD/CAM Titanium Meshes for the Guided Bone Regeneration of Severe Alveolar Ridge Defects: Preliminary Results of a Prospective Clinical Follow-up Study in Humans
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bone Resorption
Keywords: guided bone regeneration
dental implants
alveolar bone defects
custom-made
Titanium mesh
CAD-CAM
implant-supported prosthesis
autogenous bone
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2020-07-21
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aims of this prospective clinical study are to evaluate: a) the effectiveness of digitally customized titanium meshes in association with autologous bone particles and bovine bone mineral and covered with collagen membranes for the regeneration of atrophic edentulous sites; b) the survival rate of implants placed in the reconstructed areas; and c) new bone regeneration from a histomorphometric point of view

Detailed description: Objectives:

* to evaluate the effectiveness of digitally customized titanium meshes for guided bone regeneration with autologous bone chips taken from the mandibular body and/or ramus mixed with bovine bone mineral bone granules (500-1000microns in diameter):

  * complication rate of the reconstructive procedure;
  * assessment of bone gain obtained before implant placement;
* implant survival and implant-related complications 1 year after the starting of prosthetic loading;
* peri-implant bone resorption (MBL) after 1 year from the prosthetic load.
* to perform a histomorphometric analysis of bone samples taken from sites reconstructed according to the principle of Guided Bone regeneration by means of autologous bone chips mixed with a xenograft with a 1:1 ratio and customized titanium mesh.

The following parameters will be analyzed from an histologic point of view:

* bone remodeling and mineralization levels of the new bone matrix
* volumetric tissue fractions
* neo-vascularization

Study method: prospective study - 24 consecutive patients treated (see statistical power analysis)

The study will be performed in accordance with the ISO Standard 14155: 2011, Clinical Investigation of Medical Devices for Human Patients with the Appendices VIII and X of the Medical Device Directive 93/42/ EEC and following the 2004 Helsinki Declaration.

The null hypothesis (H0) is the following: the reconstructed bone is not functionally mature to support implants, masticatory and functional loads after 12 months.

The sample size calculation was performed with the statistical program https://clincalc.com/stats/samplesize.aspx. A literature search on PubMed was performed and revealed that, on average, the percentage of new bone formed after reconstructions with particulate bone autografts and xenografts and titanium mesh is 66% with a standard deviation of 6%. The expected percentage value for the investigator's study was set at 70% with a statistical power of 90% and a two-tier significance level of 0.05.

Data distribution will be analyzed by Shapiro Wilk's normality test, due to the small sample size.

If the data distribution is normal, the comparative analysis for the primary outcome will be performed by T-student test for paired samples. If the data distribution is not normal, a Wilcoxon test will be performed.

The independent variable of the study is the bone reconstruction procedure. The dependent variables are: a) the histomorphometric values of the reconstructed bone; b) the increase (measured in mm) of the bone reconstruction obtained; c) the MBL (in mm) peri-implant 1 year after the prosthetic load.

Data analysis will be performed with SPSS software. Differences will be considered statistically significant for alpha \<0.05.

Eligibility criteria: Inclusion Criteria:

* systemically healthy patients;
* a minimum age of 18 years;
* relevant or severe bone atrophy at the edentulous sites incompatible with placement of even short (≤6 mm) or narrow (\<3 mm) implants in an appropriate and prosthetically guided position;
* adequate compliance of patients, both in terms of oral hygiene and respect the follow-up recalls;
* ability to understand the proposed surgical treatment and to understand and sign the informed consent.

Exclusion Criteria:

* severe kidney and/or liver disease;
* congenital or acquired immunodeficiency;
* ongoing antiblastic chemotherapy at the time of first examination;
* sequelae of radiotherapy in the head and neck area;
* oral mucosa diseases, such as lichen planus;
* full mouth plaque score (FMPS) and full mouth bleeding score (FMBS) \< 20%;
* non-compliant patients;
* tobacco abuse (\>10 cigarettes per day) or alcohol abuse;
* non compensated diabetes;
* active periodontal disease at the time of first examination ;
* bisphosphonate chemotherapy in progress;
* pregnant women.

Primary outcomes:
measure: Histomorphometric analysis of bone samples taken from the reconstructed sites: bone remodeling and mineralization levels
timeFrame: 6-9 months
measure: Histomorphometric analysis of bone samples taken from the reconstructed sites: Volumetric tissue fractions
timeFrame: 6-9 months
measure: Histomorphometric analysis of bone samples taken from the reconstructed sites: Neo-vascularization
timeFrame: 6-9 months
measure: Effectiveness of digitally customized titanium meshes in association with autografts and xenografts for bone regeneration in resorbed jaws: Complication rate of the reconstructive procedure
timeFrame: 6-9 months
measure: Effectiveness of digitally customized titanium meshes in association with autografts and xenografts for bone regeneration in resorbed jaws: Assessment of bone gain
timeFrame: 6-9 months
measure: Effectiveness of digitally customized titanium meshes in association with autografts and xenografts for bone regeneration in resorbed jaws: Implant survival
timeFrame: 12 months
measure: Effectiveness of digitally customized titanium meshes in association with autografts and xenografts for bone regeneration in resorbed jaws: Incidence of implant-related complications
timeFrame: 12 months
measure: Effectiveness of digitally customized titanium meshes in association with autografts and xenografts for bone regeneration in resorbed jaws: Peri-implant bone resorption
timeFrame: 6-9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: ASST Santi Paolo e Carlo
Study officials:
affiliation: Department of Biomedical, Surgical and Dental Sciences
name: Matteo Chiapasco, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sagheb K, Schiegnitz E, Moergel M, Walter C, Al-Nawas B, Wagner W. Clinical outcome of alveolar ridge augmentation with individualized CAD-CAM-produced titanium mesh. Int J Implant Dent. 2017 Dec;3(1):36. doi: 10.1186/s40729-017-0097-z. Epub 2017 Jul 26.
citation: Seiler M, Kammerer PW, Peetz M, Hartmann A. Customized lattice structure in reconstruction of three-dimensional alveolar defects. Int J Comput Dent. 2018;21(3):261-267.
citation: Sumida T, Otawa N, Kamata YU, Kamakura S, Mtsushita T, Kitagaki H, Mori S, Sasaki K, Fujibayashi S, Takemoto M, Yamaguchi A, Sohmura T, Nakamura T, Mori Y. Custom-made titanium devices as membranes for bone augmentation in implant treatment: Clinical application and the comparison with conventional titanium mesh. J Craniomaxillofac Surg. 2015 Dec;43(10):2183-8. doi: 10.1016/j.jcms.2015.10.020. Epub 2015 Oct 23.