Evaluation of Effect of Bone Marrow Aspirate Concentrate on Distracted Mandibular Bone Properties
Condition: Hemifacial Microsomia; Distraction of Bone
MeSH terms: Goldenhar Syndrome; Diastasis, Bone; Fetal Growth Retardation
Study type: Interventional

Summary: 
      Maxillofacial Distraction Osteogenesis (DO) has a lot of draw backs; mostly related to long
      distraction and consolidation time. Rapid rate DO was proposed to decrease the distraction
      time to avoid consequences of long procedure. The idea of the current study is to provide
      mesenchymal stem cells (MSCs) in form of Bone Marrow Aspirate Concentrate (BMAC) during rapid
      distraction to fasten and shorten consolidation. Methods: This trial was conducted on
      patients requiring mandibular DO. Patients were divided in two groups; control group in which
      distraction took place at a rate of 1.5 mm /day without any enhancement and study group in
      which distraction took place at rate of 1.5 mm /day and the distracted bone was enhanced by
      BMAC
    

Detailed description: 
      Material and Methods:

      A prospective case-control trial was conducted on patients requiring mandibular distraction
      osteogenesis to assess the effect of BMAC on distracted bone quality. Evaluation of newly
      formed bone quantity and quality was done using a CBCT which was done post distractor removal
      as a part of routine follow up ( in agreement with European guidelines for the exposure to
      ionizing radiation) and evaluation of the bone quality was assessed by two examiners to
      provide interexaminer-reliability.

      In order to evaluate the effect of BMAC on bone maturation and possibility of early removal
      of the distractor; which was not feasible in the clinical study due to the ethical concerns.
      Mechanical three point bending was applied on distracted mandible after 30 days following
      distraction to evaluate bone healing and mechanical strength of distracted bone. In addition
      to histological and radiographic evaluation.

      Patients and methods:

      Patient grouping and anesthetic technique:

      Prospective case-control trial was conducted on patients requiring mandibular distraction
      osteogenesis. The research was reviewed by the ethical committee of author faculty. Patients
      were randomly allocated into one of the two groups (To avoid bias, each patient had a number,
      and this number was picked by the examiners (similar to a deck of shuffled cards) to assign
      the patient to his/her specific group. Control group (6 patients): control group in which
      distraction took place at a rate of 1.5 mm /day till planned length was obtained and only
      saline was injected in defect; based on the assumption that it has no effect on bone healing.
      Study group in which distraction took place at rate of 1.5 mm /day till planned length was
      obtained. Distracted bone was enhanced by injection of Bone Marrow Aspirate Concentrate
      (BMAC).

      Anesthesia was induced with IV propofol (Aspen, Ireland), 1.5-2 mg/kg, fentanyl (ADVANZ
      Pharma, United Kingdom) 1.3 μ/kg and succinyl choline (Aspen, Ireland) 1mg/kg to facilitate
      nasotracheal intubation using armored tube. Anesthesia was maintained with isoflurane (AbbVie
      Ltd, United Kingdom) in oxygen and atracurium (Accord-UK Ltd, United Kingdom) in a dose of
      0.3-0.6 mg/kg.

      BMAC preparation and harvesting:

      BMAC was harvested using the Ficoll protocol. Bone marrow was collected the iliac crest using
      bone marrow trocar. Phosphate buffered saline (PBS) was added to the aspirated bone marrow in
      a 4:1 ratio. The diluted bone marrow was titrated over Ficoll 400 (BIOCOLL; Biochrom GmbH,
      Germany), and the solution was centrifuged at a rate of 2,000 rpm for 20 minutes. The buffy
      layer pellet, which is rich in BMMSCs, was collected using a pipette. The Aspirated BMAC rich
      with MSCs was added to tissue culture flasks for till day 10 consolidation in DMEM (Thermo
      Fisher Scientific, United States) and high streptomycin-penicillin concentrate 10,000 U/mL
      (Sigma-Aldrich, United States); to be stored at -80 0C till injection at day 10 consolidation
      .

      Surgical procedure An intraoal incision was performed similar to bilateral sagittal split
      osteotomy in the last molar area area to expose the mandibular body. A piezotome was used
      with copious saline irrigation; to perform the corticotomy to avoid nerve injury. The
      osteotomy was completed using a chisel and a mallet.

      The bi-directional distractor was fixed using four 2.0 extra oral pins. Trial activation and
      deactivation were performed in operation room to be sure of osteotomy completion before wound
      closure. A topical antibacterial mouth was used throughout the entire distraction and
      consolidation period to decrease the risk of infection Postoperative phase and distraction
      protocol A topical antibacterial mouth was used throughout the entire distraction and
      consolidation period to decrease the risk of infection. Amoxicillin 875 mg. /clavulanic acid
      125 mg (Augmentin, GSK, United Kingdom) capsules twice daily for five days to decrease risk
      of infection. Ibuprofen 600 mg (Mylan Products Limited, United Kingdom) Tablets twice daily
      for three days to control pain.

      Distraction phase was performed after 5 days of latency. The rate was 1.5 mm per day till the
      planned chin position was achieved. In the study group, after 10 days of distraction, the
      prepared BMAC ( the average number of cells was 3 million) were injected in the distraction
      gap using an 18-gauge needle on days 10 of the consolidation. The control group had no
      enhancement and was considered as a negative control. The study and control groups underwent
      6 months of consolidation after then the distractor pins were removed and CBCT was performed
      to evaluate the distraction procedure. In addition to the CBCT evaluation of distraction
      results the distracted bone maturation was evaluated.

      Methods of assessment Using the CBCT (iCAT, USA) DICOM files evaluation of bone density was
      performed (at a fixed exposure value 84 Kv, 4 mA and 12 Sec ) to evaluate bone quality post
      distraction. Evaluation was done at three points located between pins marks. The first
      evaluation was done in exact center and other two readings were done 2mm before and 2mm after
      the central reading in the CT and average was calculated. Two examiners did evaluation to
      avoid bias and inter examiner reliability was measured to assess accuracy of the measurements
    

Intervention name(s): Bone Marrow Aspirate Concentrate; Saline
Intervention type(s): Other; Other
Intervention description(s): A rich MSCs prepration made by centrifugation and concentration of aspirated bone marrow; Physiological saline is added in control group to act as placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Case-control trial
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: bone marrow aspirate concentrate; Hemifacial Microsomia; Distraction osteogenesis