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Table 3 Summary of studies using membranes for segmental mandibular defects in large animal models

From: The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

Author/Year [ref]

Animal model

Type of membrane

Study design

Assessment of bone regeneration

Outcome

Jégoux

2010

[104]

Dogs

Mandible

collagen

Segmental defects after mandibulectomy using calcium phosphate ceramics and collagen membrane with a delayed bone marrow grafting (after two months, bone marrow injection)

At 16-weeks

Histological and scanning electronic microscopic analysis and X-ray microtomographic analysis

Successful osseous colonization bridged the entire length of the defects. The good new bone formation at the center and the periosteum-like formation at the periphery suggest the osteoinductive role of the bone marrow graft and the healing scaffold role of the membrane.

Borges

2009

[105]

Dogs mandible

acellular dermal matrix (ADM) in comparison with a bioabsorbable synthetic membrane

Control group (bioabsorbable membrane made of glycolide and lactide copolymer)

Test group (ADM as a membrane).

At 8 and 16 weeks, radiological evaluation

At 16 weeks: Clinical measurements of the width and thickness of the keratinized tissue and histomorphometric analysis

ADM acted as a barrier in GBR, with clinical, radiographic and histomorphometric results similar to those obtained with the bioabsorbable membrane

Sverzut

2008

[106]

Dogs mandible

poly L/DL-lactide 80/20% membrane with different permeability patterns

10 mm segmental defects

Mechanical stabilization and 6 treatment groups: control, BG alone (bone graft), microporous membrane (poly L/DL-lactide 80/20%) (Mi); Mi plus BG; microporous laser-perforated (15 cm2 ratio) membrane (Mip), and Mip plus BG.

Histological, histomorphometry and fluorescence microscopy at six months

BG protected by Mip was consistently related to larger amounts of bone versus other groups. No difference between defects treated with Mip alone and BG alone. Mi alone rendered the least bone area and reduced the amount of grafted bone to control levels. Bone formation was incipient in the BG group at three months regardless of whether or not it was covered by membrane. In contrast, GBR with Mip tended to enhance bone formation activity at three months.

The use of Mip alone could be a useful alternative to BG. The combination of Mip membrane and BG efficiently delivered increased bone amounts in segmental defects compared with other treatment modalities.

Bornstein

2007

[107]

Dogs mandibles

two bioabsorbable collagen membranes:

collagen membrane versus cross-linked collagen membrane (CCM).

three standardized defects filled with bone chips and deproteinized bovine bone mineral (DBBM), and covered by three different methods: control = no membrane; test 1 = collagen membrane; and test 2 = cross-linked collagen membrane (CCM). Each side of the mandible was allocated to one of two healing periods (8 or 16 weeks).

At 8 and 16 weeks

Histomorphometric analysis

For all groups, the defect fill height increased between weeks 8 and 16. The CCM group showed a statistically significant increase over time and the highest value of all treatment modalities after 16 weeks of healing. The CCM showed a limited beneficial effect on bone regeneration in membrane-protected defects in dog mandibles when healing was uneventful. However, the increased complication rate with CCM requires a more detailed preclinical and clinical examination.

Zubery

2007

[108]

Dogs mandibles

type I collagen membrane (GLYM) using a novel cross-linking technology versus a non-cross-linked bilayer type I and III collagen membrane (BCM)

Mandibular bilateral critical size defects

five groups: GLYM + bovine bone mineral (BBM), BCM + BBM, BBM alone, sham-operated, or GLYM alone.

At 8, 16, and 24 weeks, Qualitative, semiquantitative, and quantitative light microscopy analyses

Membrane-protected sites displayed bone filling between the BBM particles with almost complete restoration of the original ridge morphology that increased with time up to 16 weeks and remained unchanged at 24 weeks. Both membranes showed marked degradation within 16 to 24 weeks, with BCM inconsistency that was undetectable in one of four sites at 8, 16, and 24 weeks. Membrane ossification was observed in all GLYM sites and in only one BCM site, which progressed with time to 24 weeks. Bone increased by approximately 1 mm on the lingual side, where the GLYM membrane was in direct contact with bone.

Peled

2002

[109]

Dogs mandibles

titanium-reinforced expanded ePTFE membrane (ePTFE-TR)

Mandibulectomy defects (25 mm × 15 mm)

ePTFE-TR or control (repositioning flaps)

At four to six months

Macroscopic and histological/histomorphometric evaluation

The size of the residual defect in the experimental sites was much smaller compared to the controls, which was statistically significant. Histomorphometric measurements of new bone formation revealed a similar pattern. These differences were also statistically significant.

Fritz

2000

[110]

Macaca mulatta monkeys

Mandibles

reinforced ePTFE membranes

Standardized 8 × 19 mm mandibular defects Reinforced ePTFE membranes held in place with mini screws and sutures for anywhere from 1 to 12 months. No material added to the defect.

Digital subtraction radiology and fluorescent labelling with tetracycline and histomorphometry

Data suggest that membranes left in situ for 1 month or less result in minimal bone gain compared with membranes left in place from 2 to 12 months. In addition, labelling and stained sections clearly showed that the bone produced after 2 months of membrane placement is mature.

Schenk

1994

[22]

Dogs mandibles

standard and prototype reinforced e-PTFE membranes

Standard and prototype reinforced e-PTFE membranes and control (no membranes)

At two and four months

Histologic evaluation

Control sites without membranes exhibited incomplete osseous healing with a persisting defect. Test sites with membranes demonstrated significantly better bone healing, although bone regeneration was not yet completed at 4 months. Histologic evaluation showed that bone regeneration, once activated, progresses in a programmed sequence which closely resembles the pattern of bone development and growth.