Table 2 Summary of studies using membranes for segmental mandibular defects in small animal models

Kazakos

2011

[95]

Rabbits mandible

platelet-rich plasma (PRP) gel alone or human fascia lata membrane (HFL)

Group I: HFL

Group II: PRP gel

Group III: HFL+PRP

Histological at 12 weeks

None of the control sides and the PRP treated sides had full development of bone or filling of the defect through bone bridging.

The application of PRP gel alone or in combination with HFL does not seem to enhance bone regeneration.

Kim

2011

[64]

Rats mandible

a novel nanofibrous membrane of a degradable biopolymer poly (lactide-co-ε-caprolactone) (PLCL)

A 5 mm critical-sized defect

Histological at four weeks

The assessment of cell compatibility showed favorable cell adhesion and growth on the nanofiber PLCL membrane. At four weeks, the PLCL nanofibrous membrane induced better guided new bone formation than the defect control group while protecting the bone defect against the ingrowth of fibrous tissues.

Hoogeveen

2009

[96]

Rats mandible

a degradable membrane of poly(DL-lactide-epsilon-caprolactone) (PDLLCL) versus collagen versus polytetrafluoroethylene (ePTFE)

Defects covered with a membrane (PDLLCL, collagen, or expanded ePTFE) or left uncovered (control).

At 2, 4 and 12 weeks using transversal microradiography

For defect closure and bone thickness all membrane-treated groups showed effect modification between time and membrane; these effects were more significant and larger in the collagen and ePTFE groups. In the non-treated controls no effect modification was observed. The membrane groups showed significantly better results than the control groups. The ePTFE and collagen membranes performed equally well and better than the PDLLCL membrane during this experiment. PDLLCL membrane not suitable for clinical application in its current form.

Gielkens

2008

[31]

Rats

Mandible

a novel degradable synthetic membrane (Vivosorb) of poly(dl-lactide-epsilon-caprolactone) (PDLLCL)

versus collagen and ePTFE membranes

A standardized 5 mm circular mandibular defect

Four groups (control/uncovered, PDLLCL, collagen, ePTFE).

At 2, 4, and 12 weeks

Microradiography and muCT

Bone formation was progressive when the defect was covered with a membrane. More bone formation was observed underneath the collagen and ePTFE membranes than the PDLLCL membranes.

Bone formation in PDLLCL-covered defects was less and the high variation in the PDLLCL samples at 12 weeks may be caused by the moderate adherence of this membrane to bone compared with collagen.

He

2008

[97]

Rabbits mandible

a novel calcium alginate film (CAF) versus conventional collagen membrane (CM)

Bilateral critical size 5 mm mandibular defects

covered with CAF (experimental group) or conventional collagen membrane (CM) or left empty (control group)

At one, two, four, six and eight weeks. Morphological and histomorphometric evaluation

The CAF guided early bone growth and appeared more effective as a bioabsorbable GTR membrane than CM.

A significantly greater percentage of newly generated bone in CAF defects than that in CM defects and empty defects from two to six weeks post-operation.

At six and eight weeks, significantly more mature lamella bone had formed with CAF than with CM.

Thomaidis

2008

[34]

Rabbit mandible

five different membranes:

- HFL (human fascia lata)

- HP (human pericardium)

- HFT (human fascia temporalis)

- BP (bovine pericardium),

- e- PTFE

9-mm circular mandibular defects were created bilaterally.

Five groups for each membrane and the defect on the other side served as a control.

Histological at ten weeks

Membranes were significantly superior to the controls.

HFL, HP, BP, and PTFE were significantly superior to HFT

HFT is not recommended for GBR techniques for osseous defects beyond the critical size.

Asikainen

2006

[54]

Rabbit mandible

poly(desaminotyrosyl-tyrosine-ethyl ester carbonate) (PDTE carbonate) membrane (thickness 0.2-0.3 mm)

A through-and-through defect (12 × 6 mm).

Group 1: defects left unfilled but covered with membrane

Group 2: defects filled with bioactive glass mesh and covered with membrane

Controls were left uncovered and unfilled.

Histological at 6, 12, 24 and 52 weeks

PDTE carbonate elicited a modest foreign body reaction in the tissues, which was uniform throughout the study. New bone formation was seen in all samples after six weeks. Group 1 had more new bone formation until 24 weeks and after this the difference settled. PDTE carbonate membranes have good biocompatibility and are sufficient to enhance bone growth without additional supportive matrix.

Jianqi

2002

[63]

Rabbit mandible

calcium alginate film (CAF) with CM

Circular bone defects with 5-mm diameter one side were covered with a CAF, and the contralateral side with CM.

gross, radiographic, electromicroscopic, histologic, and immunohistochemical analyses and image pattern analysis system at one, two, four, six, and eight weeks

CM absorbed more slowly but collected fewer osteoinductive factors (P < .05) in the early period. CAF induced dense bone formation, whereas CM produced less newly formed bone.

CAF is more efficacious than CM in guided bone regeneration in this animal model.

Stetzer

2002

[94]

Rabbit mandible

collagen membrane

Bilateral critical size (4 mm) defects maxillary segments were rigidly or not rigidly fixed using bone microplates and screws or osteosynthetic wires. The defects were covered with a resorbable collagen membrane or left uncovered.

At four weeks

serial radiographs and histologic/histomorphometric analyses

The rigidly fixed defects, covered with membrane, showed the most rapid and organized new bone formation. They averaged approximately 40% more new bone in the osteotomy site compared with the rigidly fixed defects with no membrane. No rigidly fixed defects with no membrane showed an ingrowth of fibroblasts and fibrous non-unions.

Zahedi

1998

[98]

Rats mandible

diphenylphosphorylazide-crosslinked type I bovine collagen membrane

(DPPA)

5 mm diameter full-thickness circular bone defects

one side covered by the membrane

the other side uncovered (control)

Histological at 7, 15, 30, 90, and 180 days

Although at early stages of healing similar amounts of bone formation were observed in the both groups, after one month of healing, most of the experimental defects were completely closed with new bone, while in the control defects, only limited amounts of new bone were observed at the rims and in the lingual aspect of the lesions. In the 90- and 180-day animals, all experimental defects were completely closed, while in the control defects, no statistically significant increase in bone regeneration was observed.

Linde

1995

[99]

Rats mandible

e-PTFE membrane

(GORE-TEX)

Circular transosseous 'critical size' defects in mandibles of rats were either implanted with recombinant human bone morphogenetic protein type 2 (rhBMP-2) or were left empty; half the number of implanted and half the number of empty defects were covered with the e-PTFE membrane

At 12 and 24 days of healing by a histomorphological scoring system

Implantation of rhBMP-2 alone resulted in bony bridging of the defect after only 12 days, but also in voluminous amounts of new bone outside the original defect area. When rhBMP-2 was combined with membrane, newly formed woven bone bridged the defect and the bone contour was maintained by the membrane. The combined treatment with membrane and rhBMP-2 demonstrated a significantly better bone healing than with e-PTFE membrane alone at both 12 days and 24 days of healing. RhBMP-2 had a strong osteoinductive potential and this potential was retained when combining the rhBMP-2 with the osteopromotive membrane technique, yielding better bone healing than with the membrane alone, and at the same time maintaining the bone contour.

Zellin

1995

[100]

Rats mandible

ten different biodegradable and non-biodegradable membrane materials

Standardized bilateral critical size mandibular defects and randomly covered with the different types of membrane

Scanning electron microscopy and histological analysis at six weeks

At six weeks, varying degrees of bone healing seen beneath the different membranes. Some of the membranes revealed a good osteopromotive effect, whereas others had little or no beneficial effects on bone healing, even if seemingly chemically closely related. Certain membrane materials caused a pronounced inflammatory response in the surrounding soft tissue, while others displayed a low inflammatory reaction.

Dahlin

1994

[101]

Rats mandible

e-PTFE membrane

Standardized through-and-through critical size defects (non-union)

On one side of the jaw, the defect was covered both buccally and lingually with an expanded polytetrafluoroethylene (e-PTFE) membrane.

On the other side no membrane was used.

Histological at six weeks

Complete healing with bone of the membrane-covered defects at six weeks. No cartilage was present in any of the specimens. At the control sites (no membrane), the amount of newly produced bone showed variations, most through defects revealing the presence of a remaining central portion of connective tissue.

Kostopoulos

1994

[102]

Rats mandible

a polyhydroxybutyrate resorbable membrane

A 2 × 3 mm defect

the contralateral side: no membrane

Histological analysis from 15 days to 6 months

The histological analysis demonstrated increasing bone fill in the test specimens from 15 to 180 days, whereas only 35% to 40% of the defect area in the control sides was filled with bone after 3 to 6 months. Ingrowth of muscular, glandular and connective tissue was consistently occurring in the control defects during healing.

Sandberg

1993

[103]

Rats mandible

three types of bioabsorbable membranes (BAMs) of polylactic/polyglycolic acid copolymers with different absorption times and comparisons with e-PTFE membrane.

Standardized 5 mm critical size defects

Histological at 1 to 12 weeks

BAMs were well tolerated by the tissue, causing just a mild inflammatory reaction along the membrane surfaces as long as the material remained in the tissue. The BAMs were as efficient as e-PTFE membranes. Healing in conjunction with one type of BAM seemed to occur somewhat more rapidly. BAMs represent a valid alternative to e-PTFE membranes to improve bone regeneration.