Three-dimensional Bone Regeneration Using Custom-made Meshes With and Without Collagen Membrane
Condition: Surgical Procedure, Unspecified; Soft Tissue Infections; Surgical Wound Dehiscence; Bone Density; Bone Loss in Jaw
MeSH terms: Soft Tissue Infections; Surgical Wound Dehiscence; Surgical Wound
Study type: Interventional

Summary: 
      The presence of alveolar ridge deficiencies is considered major limitation to achieve an
      implant-prosthetic restoration with high aesthetics and stability over time. Guided Bone
      Regeneration (GBR) can be considered an effective solution for bone augmentation. The most
      advanced technology of GBR is the customized titanium mesh, which is developed with a fully
      digital work flow system. The aim of this study is to evaluate complications and bone
      augmentation rates after GBR, based on customized meshes with or without collagen membranes.

      After ethical committee approval, 30 patients with horizontal and/or vertical bone defects
      were enrolled and treated according to the study protocol. During reconstructive surgery
      (T0), patients were randomly divided into two study groups: 15 patients were treated by means
      of a custom-made mesh without collagen membrane (Group A - Control Group), while 15 patients
      were treated by means of a custom-made titanium mesh with a collagen membrane (Group B - Test
      Group). All sites were grafted with a mixture 50:50 of autogenous bone and xenograft and
      primary closures of surgical sites were obtained to ensure a submerged healing of the meshes.
      After 6 months (T1), re-entry surgery was completed to remove the meshes, evaluate the
      augmented volume and to place implants in the augmented sites. After 3 months (T2), soft
      tissue management was accomplished with implant exposure and a connective tissue graft,
      before prosthetic restoration (T3). Data collection included surgical and healing
      complications, planned bone volume (PBV) and reconstructed bone volume (RBV),
      pseudo-periosteum type, bone density, implant success, and crestal bone loss. A statistical
      analysis of recorded data was performed to investigate any statistically significant
      differences between the study group and statistical significance was set at a=0.05.
    

Detailed description: 
      The rationale of the study is based on the fact that manual and intraoperative modeling of an
      osteosynthesis mesh is an employee operator and even in the case of very experienced
      operators it is always difficult, inaccurate and slow. The use of this pre-modeled and
      pre-fabricated custom-made mesh with bevel margins and three-dimensionally morphology adapted
      to the bone defect, would allow for a congruous bone regeneration reducing the operating
      times, the risks linked to the mesh trauma, and the discomfort for the patient. The collagen
      membrane in association with titanium, based on the principles of guided bone regeneration
      (GBR), would make it possible to increase bone gain and reduce the percentage of early and
      late exposure of the mesh.

      This study aims to evaluate, in cases of maxillary and mandibular atrophies characterized by
      a vertical and / or horizontal resorption of the alveolar bone, the percentage of
      complications (intra- and post-operative) after bone regeneration using custom-made mesh with
      or without collagen membrane.

      The primary objective of this study is to evaluate the non-inferiority of technique B
      (custom-made mesh - without membrane) compared to technique A (custom-made mesh - with
      membrane) in the incidence of complications.

      Secondary objectives include evaluation of the missing bone volume (lacking bone volume or
      LBV), reconstructed bone volume (reconstructed bone volume or RBV) with respect to planned
      bone volume (planned bone volume or PBV), histological and histomorphometric analysis at the
      time removal of the mesh and peri-implant bone resorption, due to the functional loading of
      the implants, at 12 months of follow-up.

      Other objectives include the qualitative evaluation of bone regeneration by histological and
      histomorphometric analysis upon removal of the mesh; and the evaluation of peri-implant bone
      resorption, due to the functional loading of the implants, at 12 months of follow-up.

      This is a clinical trial which is promoted by Prof. Claudio Marchetti and the University
      Hospital of Bologna - Policlinico Sant'Orsola Malpighi. The study is designed as a pilot,
      randomized, monocentric, independent, parallel-group clinical trial, in which the variables
      will be analyzed prospectively.

      The study will have a selection and enrollment period of approximately 12 months; a treatment
      period of about 12 months. As a result, the overall duration of the study will be around 24
      months.

      In the two-year period 2017/2019 the study will include the treatment of 30 patients, in good
      general health, suffering from partial edentulism of the maxilla and / or jaw with vertical
      and / or horizontal resorption of the alveolar bone, which require prosthetic rehabilitation
      supported by implants to improve function and aesthetics of edentulous areas.

      Patients will be divided into 2 study groups and assigned to each study group based on the
      previously computer-generated randomization sequence: 15 patients (group A, control) will be
      treated by bone regeneration with custom-made mesh without a collagen membrane. 15 patients
      (group B, test) will be treated by bone regeneration with custom-made mesh with collagen
      membrane.

      In the following table, the 3 treatment phases: The first phase (T0) involved bone
      regeneration with a custom-made mesh (group A) and with collagen membrane (group B); the
      second one (T1), subsequently, after 6 months: will forsee the removal of the regeneration
      device and the insertion of the implants; the thirt (T2), 3 months after the aforementioned,
      will forsee the final functional loading of the implants, with a consequent follow-up of the
      regenerated bone.

      All the materials and tools that will be used in the study are CE certified (with the
      exception of the custom-made mesh which, as a custom-made device, does not require CE
      certification) and have already been used in the normal care path for patients who have
      undergone bone regeneration. Moreover, the control visits and the radiological investigations
      of the data foreseen by the aforementioned protocol will be collected; They will be
      summarized in the case report form (CRF), and are those that characterize the normal care
      path of patients undergoing necessary bone regeneration for prosthetic implant rehabilitation
      when the bone quantity is insufficient.

      The primary objective of this study is to evaluate the non-inferiority of technique B
      (digital technique) compared to technique A (traditional technique) in the incidence of
      complications.

      The Secondary objectives include: assessment of patient and operator benefits, reconstructed
      bone volume (RBV) compared to planned bone volume (PBV), histological and histomorphometric
      analysis of bone quality obtained and peri-implant bone resorption after 12 months of
      follow-up.

      The sample size necessary to support the null hypothesis is 17 subjects for each group. In
      order to compensate for any protocol deviations or possible drop-outs, the number of patients
      was increased to 15 per group.

      The results obtained in the two study groups will be subjected to descriptive statistical
      analysis and the differences between groups will be tested by means of appropriate
      statistical tests for purely exploratory and non-demonstrative purposes.

      The patient will be considered as the statistical unit of the analysis, and the statistical
      significance will be set at α = 0.05.

      The collected data will be grouped and summarized with respect to the demographic,
      anamnestic, and clinical variables of each patient.

      Exploratory analyses will be performed using descriptive statistics. The data will be
      presented both for the intent-to-treat population and for the per-protocol population.

      The sample size necessary to support the null hypothesis is 17 subjects for each group. In
      order to compensate for any protocol deviations or possible drop-outs, the number of patients
      was increased to 15 per group. The sample size was calculated using dedicated statistical
      software (STATA, StataCorp LLC) through Pearson's chi-squared test, guaranteeing a level of
      significance of 95% and a power of 80%.
    

Intervention name(s): Bone augmentation with cad-cam laser-sintered mesh
Intervention type(s): Device
Intervention description(s): Titanium meshes cad cam laser-sintered were applied in sites with alveolar bone deficiency in order to regenerate the bone volume in need of implant-prosthetic restorations.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment