Perforated Barrier Membranes Maintain Physiologic Gingival Crevicular Fluid Growth Factor Levels
Condition: Vascular Endothelial Growth Factor Overexpression; Membrane Alteration
Study type: Interventional

Summary: 
      Membrane modifecation:

      Guided tissue membrane perforations may serve as a more biologic scaffold that could allow
      for the free passage of biologic mediators from the periosteum and overlying gingival
      connective tissue into the periodontal defects.

      Study hyposethis:

      To test this hyposthesis, this study was designed to evaluate levels of vascular endothelial
      cell growth factors and platlet derived growth factors in gingival crevicular fluid (GCF)
      during the early stages of healing for localized intrabony defects treated with modified
      perforated membranes (MPMs), occlusive membranes (OMs) as compared to open flap debridement
      control (OFD).

      Methods: Thirty non-smoking patients with severe chronic periodontitis participated in this
      prospective, randomized and single blinded trial. Each patient contributed one interproximal
      defect that was randomly assigned to experimental modified perforated membrane group (10
      sites), occlusive membrane group (10 sites) or open flap debridement control (10 sites).
      Plaque index, gingival index, probing depth (PD), clinical attachment level (CAL) and the
      intrabony depth of the defect (IBD) were measured at baseline for patients enrollment.
      Gingival crevicular fluid (GCF) samples were collected on day 1 and 3, 7, 14, 21, and 30 days
      after therapy. The primary outcome variable was the change in VEGF and PDGF-BB levels for
      sites treated by MPMs or OM compared to that of the OFD treated cases.
    

Detailed description: 
      surgical procedures:

        -  All surgeries were performed by the same operator (AYG).

        -  The surgical treatment phase was initiated only if the subject had a full-mouth dental
           plaque score of less than one and site plaque score of 0.

        -  Surgical procedures were accomplished as described in detail by Gamal and Iacono. 14
           Under local anesthesia, a mucoperiosteal flap was elevated starting with an internal
           bevel incisions to the mucogingival junction to allow passive closure. Debridement of
           all inflammatory granulation tissue from the intrabony defect was performed by means of
           Gracey 7/8 metal curettes until a sound, healthy bone surface was obtained. At this time
           point, teeth were thoroughly root planed combining the use of metal curettes and
           power-driven instrumentation.

        -  For MPM treated sites, collagen membrane perforations were prepared just before surgery
           using a custom made 1 mm diameter pin and 1mm perforated acrylic template with a coronal
           occlusive rim of about 3 mm . Inter-perforation spaces were determined to be not less
           than 2mm in order to avoid loss of membrane stiffness. Thereafter, collagen membranes
           were hydrated in sterile saline, trimmed according to the template prepared for each
           defect, and adapted over the defects in such a manner that the entire defect and ≥2 of
           the surrounding alveolar bone was completely covered to avoid membrane collapse within
           the defect. The membranes were extended supracrestally 1 mm below the CEJ to ensure
           optimum gingival CT involvement in supracrestal wound healing. Collagen membranes were
           simply adapted in place according to the surgical protocol of the manufacturer without
           suturing. The mucoperiosteal flap was coronally positioned covering the entire membrane
           and sutured with 5-0 non-resorbable suture .

        -  No periodontal dressing was applied. OM and OFD sites were treated the same way except
           for using occlusive membranes or defect closure without using membranes. All patients
           received oral and written postoperative instructions.

        -  Patients were prescribed amoxicillin (500 mg)‡ every 8 hours for 1 week. Subjects with
           allergies to amoxicillin and derivatives were prescribed Clindamycin (300 mg) every 8
           hours.

        -  Plaque control effort was supplemented by rinsing with chlorhexidine (0.12%
           chlorhexidine hydrochloride §) for one minute three times daily for 2 weeks. The
           patients were instructed to refrain from tooth brushing and interdental cleaning was
           avoided at the surgical areas during this time.

        -  Sutures were removed 14 days postoperatively and recall appointments for observation of
           any adverse tissue reaction and oral hygiene reinforcement were scheduled every second
           week during the first 2 months after surgery.

        -  One month after surgery, all patients were instructed to resume their normal mechanical
           oral hygiene measures, which consisted of brushing using a soft toothbrush with a
           roll-technique and flossing. Supportive periodontal maintenance including oral hygiene
           reinforcement and supragingival scaling was performed during each recall appointment.

      Gingival Crevicular Fluid (GCF) Sampling:

      To avoid irritation, samples were obtained 1 day following surgery and after individuals had
      fasted overnight and between 8:00AM and 10:00AM.

        -  Using micropipettes (5 ul), GCF samples were collected 21 by a single examiner (MA) who
           was masked to the attribution of the sites to groups.

        -  Following the isolation and drying of the selected site with cotton rolls, a fisher
           brand disposable micropipettes € was placed intrasulcularly at the mesiofacial line
           angle of the selected site to a maximum depth of 2 mm below the gingival margin.
           Micropipettes were left in place until 5 µl of fluid was collected.

        -  GCF samples were collected at day 1, 3, 7, 14, 21, and 30 days after therapy and diluted
           in saline solution (50 µl) for evaluation of VEGF and PDGF-BB levels. Samples were
           labeled, carried in a dark container and kept at -26 C until used.
    

Intervention name(s): collagen membrane; collagen membrane
Intervention type(s): Device; Device
Intervention description(s): bovine collagen membrane used for selective tissue regeneration; collagen bovine occlusive membrane for selective tissue regneration
Other intervention name(s): guided tissue membranes; guided bone regeneration; occlusive membranes; guided tissue membranes; resorbable membranes; guided bone regeneration
Intervention model: Single Group Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: growth factors; periodontal regeneration; modefied perforated membranes