J Clin Periodontol 2008; 35 (Suppl. 8): 106–116 doi: 10.1111/j.1600-051X.2008.01263.

Regeneration of periodontal Anton Sculean1, Dimitris Nikolidakis1

and Frank Schwarz2
1
Department of Periodontology Radboud

tissues: combinations of barrier University Medical Center, Nijmegen, The

Netherlands; 2Department of Oral Surgery,
Heinrich Heine University, Düsseldorf,

membranes and grafting Germany

materials – biological foundation

and preclinical evidence
A systematic review
Sculean A, Nikolidakis D, Schwarz F. Regeneration of periodontal tissues:
combinations of barrier membranes and grafting materials – biological foundation
and preclinical evidence. A systematic review. J Clin Periodontol 2008; 35 (Suppl. 8):
106–116. doi: 10.1111/j.1600-051X.2008.01263.x.

Abstract
Background: Regenerative periodontal therapy aims to predictably restore the tooth’s
supporting periodontal tissues and should result in formation of a new connective
tissue attachment (i.e. new cementum with inserting periodontal ligament fibres) and
new alveolar bone. Histologic evidence from preclinical models has demonstrated
periodontal regeneration following treatment with barrier membranes, various types of
grafting materials or a combination thereof. However, it is still not clear to what extent
a combination of barrier membranes and grafting materials may additionally enhance
the regeneration process compared with barrier membranes alone, grafting materials
alone or open flap debridement.
Objectives: To review with a systematic approach all preclinical (i.e. animal) studies
presenting histologic support for periodontal regeneration using the combination of
barrier membranes and grafting materials.
Material and Methods: Based on a focused question, an electronic and manual search
was conducted for animal studies presenting histological data for the effect of the
combined use of barrier membranes and grafting materials on the treatment of
periodontal defects. A systematic approach was followed by two independent reviewers
including eligibility criteria for study inclusion, outcome measures determination,
screening method, data extraction, data synthesis and drawing of conclusions.
Results: Ten papers completely fulfilling the inclusion criteria were selected. All
relevant data from the selected papers were extracted and recorded in separate tables
according to the types of periodontal defects treated (i.e. supra-alveolar defects,
intrabony defects, furcation defects and fenestration defects) with the combination of
barrier membranes and grafting materials. Most studies have demonstrated periodontal
regeneration following the combination approach. Most studies demonstrated superior
histologic healing following the combination of barrier membranes and grafting
materials than following open flap debridement. Histologically superior healing
following the combination of barrier membranes and grafting materials when
compared with barrier membranes alone or grafting materials alone were only obtained
in non-contained two wall intrabony and supraalveolar defects.
Conclusion: Within its limits the present analysis indicates that:
(a) The combination of barrier membranes and grafting materials may result in
histological evidence of periodontal regeneration, predominantly bone repair.
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 Barrier membranes and grafting materials in regenerative periodontal therapy 107

(b) No additional benefits of combination treatments were detected in models of three

wall intrabony, Class II furcation or fenestration defects.
(c) In supra-alveolar and two wall intrabony (missing buccal wall) defect models of Key words: animal models; barrier
membranes; grafting materials; histology;
periodontal regeneration, the additional use of a grafting material gave superior
preclinical models; regenerative periodontal
histological results of bone repair to barrier membranes alone. therapy
(d) In one study using a supra-alveolar model, combined graft and barrier membrane
gave a superior result to graft alone. Accepted for publication 20 May 2008

Conflict of interest and source of 1. Contain bone-forming cells (osteo- Gottlow et al. 1984). On the other hand,
funding statement neogenesis). the amount of regenerated tissues is
The authors declare that they have no 2. Serve as scaffold for bone formation limited by the available space under
conflict of interests. (osteoconduction). the membrane, thus suggesting that the
The 6th European Workshop on Perio- 3. Contain bone-inducing substances space-provision and wound-stabilizing
dontology was supported by an unrestricted (osteoinduction) (Brunsvold & Mel- effects of the barrier membrane may
educational grant from Straumann AG. lonig 1993). substantially influence the healing pro-
cess (Wikesjö & Nilvéus 1990, Haney
On the other hand, recent evidence et al. 1993). One way in which clini-
Regenerative periodontal therapy aims from preclinical studies using the criti- cians attempt to overcome the problems
to predictably restore the tooth’s sup- cal-size supraalveolar defect has sug- related to a collapse of the barrier
porting periodontal tissues (i.e. new gested that the main mechanism by membrane is the use of a combination
periodontal ligament, new cementum which certain grafting materials appear of barrier membranes and grafting
with inserting periodontal ligament to support periodontal and bone regen- materials. However, the data from con-
fibres and new bone) that have been eration when used in combination with trolled clinical studies do not seem to
lost due to periodontal disease or dental guided tissue regeneration (GTR) is clearly indicate improved clinical out-
trauma (Polimeni et al. 2006). Nonsur- rather by space provision than by the comes in terms of probing depth reduc-
gical and conventional surgical perio- osteoconductive properties of the graft- tion, clinical attachment level (CAL)
dontal therapy may usually result in ing material (Polimeni et al. 2004). gain and defect fill when the combina-
successful clinical outcomes such as Histological findings from a series of tion of grafting materials and GTR is
probing depth reduction and gain of animal experiments have demonstrated compared with GTR alone or grafting
clinical attachment. Histologically, how- the important role of periodontal liga- materials alone (Blumenthal & Stein-
ever, the healing following these treat- ment cells in creating a new connective berg1990, Chen et al. 1995, Mellado et
ment approaches was characterized by a tissue attachment (i.e. new periodontal al. 1995, Gouldin et al. 1996, Trejo et
long junctional epithelium along the ligament and new cementum with al. 2000, Paolantonio 2002, Murphy &
treated root surfaces and no formation inserting periodontal fibres) (Löe & Gunsolley 2003, Nygaard-Østby et al.
of cementum with an associated perio- Waerhaug 1961, Melcher 1976, Karring 2008).
dontal ligament (Caton & Greenstein et al. 1980, 1984, 1985, Nyman et al. From a biological point of view, the
1993). Although in some cases a con- 1980, Lindhe et al. 1984, Isidor et al. use of any type of regeneration method
ventional periodontal therapy may result 1985). These studies have also indicated needs to be supported by histologic
in bone regrowth, histological studies that the potential of periodontal liga- evidence from preclinical (i.e. animal)
have demonstrated that an epithelial lin- ment cells for forming a new connective experiments, thus supporting its ratio-
ing was often interposed between the tissue attachment could only develop if nale (Polimeni et al. 2006).
root surface and the newly formed the epithelium and the gingival connec- The aim of this study is to review with
bone (Caton & Greenstein 1993). tive tissue were prevented from occupy- a systematic approach all preclinical (i.e.
One widely used technique in recon- ing the wound area adjacent to the root. animal) studies presenting histologic
structive periodontal surgery is the use Other observations from preclinical support for periodontal regeneration
of various types of grafting materials to studies evaluating treatment of experi- using combination therapy of barrier
fill the periodontal defects (Brunsvold & mentally-created intrabony defects via membranes and grafting materials.
Mellonig 1993). Data from systematic implantation of different types of graft-
reviews have suggested that the implan- ing materials or flap surgery have shown
tation of grafting materials may indeed a healing characterized by formation of
result in superior clinical outcomes in a long junctional epithelium until the Material and Methods
terms of probing depth reduction and most apical part of the instrumented root Development of a protocol
clinical attachment gain compared with surface and no periodontal regeneration
open flap debridement (Trombelli et al. (Caton et al. 1980). The placement of a A protocol was developed before com-
2002, Reynolds et al. 2003). barrier membrane (i.e. GTR) over the mencing the review and covered all
The biologic rationale for using graft- denuded root surfaces and the debrided aspects of the systematic review metho-
ing materials is based on the assumption periodontal defect has been shown to dology (Needleman 2002). These aspects
that these materials may facilitate for- exclude epithelial downgrowth and were: definition of a focused question,
mation of alveolar bone, periodontal allow periodontal ligament and alveolar search strategy, eligibility criteria for
ligament and root cementum through bone cells to repopulate the isolated study inclusion, outcome measures deter-
one of the following mechanisms: space selectively (Nyman et al. 1982, mination, screening methods and data
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Journal compilation r 2008 Blackwell Munksgaard
108 Sculean et al.

extraction, data synthesis and drawing Table 1. Searching terms were used to identify the proper studies
of conclusions.
Searching terms:
(‘‘periodontal defect’’ OR ‘‘periodontal lesion’’ OR ‘‘periodontal osseous defect’’ OR
‘‘intraosseous defect’’ OR ‘‘intra-osseous defect’’ OR ‘‘intrabony defect’’ OR ‘‘intra-bony
Definition of a focused question
defect’’ OR ‘‘infrabony defect’’ OR ‘‘infra-bony defect’’ OR ‘‘angular defect’’ OR ‘‘furcation
The question addressed was the follow- defect’’ OR ‘‘furcation invasion’’ OR ‘‘furcation involvement’’)
ing: what is the effect of the combina- AND
tion of barrier membranes and grafting
materials on the healing of periodontal (‘‘guided tissue regeneration’’ OR ‘‘GTR’’ OR ‘‘membrane’’ OR ‘‘barrier’’ OR ‘‘periodontal
regeneration’’)
defects in animal studies?
AND

Search strategy (‘‘bone graft’’ OR ‘‘bone replacement graft’’ OR ‘‘bone substitute’’ OR ‘‘osseous graftn’’OR
‘‘bone transplantation’’ OR ‘‘bone regeneration’’ OR ‘‘bone matrix’’OR ‘‘autologous bone
Literature search, for articles published graftn’’ OR ‘‘autogenous bone graftn’’ OR ‘‘allogenic bone graftn’’ OR ‘‘allograft’’OR ‘‘freeze-
up to and including November 2007, dried bone allograftn’’ OR ‘‘demineralized freeze-dried bone allograftn’’ OR ‘‘decalcified
was performed using MEDLINE data- freeze-dried bone allograftn’’ OR ‘‘bovine bone’’ OR ‘‘synthetic graft’’ OR ‘‘polymer’’ OR
base. Combinations of searching terms ‘‘ceramic graftn’’ OR ‘‘bioactive ceramic graftn’’ OR ‘‘bioglassn’’ OR ‘‘bioglass graftn’’ OR
‘‘bioceramicn’’ OR ‘‘hydroxyapatites’’ OR ‘‘calcium phosphate’’ OR ‘‘tricalcium phosphate’’
were used to identify the proper studies OR ‘‘beta-tricalcium phosphate’’ OR ‘‘tricalcium phosphate’’ OR ‘‘ceramicn’’ OR ‘‘calcium
(Table 1). carbonate’’ OR ‘‘calcium sulfate’’ OR ‘‘Plaster of Paris’’)
Also the reference lists of review arti-
cles were scanned. In addition, the refer- AND
ence lists of articles selected for inclusion (‘‘animal model’’ OR ‘‘animal study’’ OR ‘‘preclinical study’’ OR ‘‘dog study’’ OR ‘‘monkey
in the present review were screened. study’’ OR ‘‘rabbit study’’ OR ‘‘rat study’’)
Finally, a hand searching including the
Journal of Dental Research, Journal of
Clinical Periodontology, Journal of
 Change in CAL or change in prob- mined by k scores. Authors of the trials
Periodontology, Journal of Periodontal
ing pocket depth in millimetres after were contacted to provide missing data
Research and The International Journal
clinical evaluation. where possible.
of Periodontics and Restorative Dentistry
Data were extracted based on the
was performed. When specific data were reported, defect general characteristics (authors and
resolution and defect fill were calculated. year of publication), study characteris-
Criteria selection for study inclusion tics (type and number of animals; tooth
Also, secondary outcomes were type; defect characteristics; intervention
The selection was limited to animal evaluated as: strategies; evaluation period; outcome
studies evaluating the combined use of measures; complications), methodologi-
barrier membranes and grafting materi-  adverse effects related to the addi- cal characteristics (study design and
als for the treatment of periodontal tional use of barrier membrane/ methodological quality) and conclusions.
defects. Any type of barrier membrane grafting materials
and grafting material was considered.  post-operative complications
Studies involving biomimetic sub- Data analysis
stances/growth factors were excluded. Screening methods and data extraction There was a substantial heterogeneity in
A time limitation of 4 weeks regarding The titles and abstracts were indepen- the data collected regarding animal type,
postoperative evaluation period was dently screened by two reviewers (A. S. study design, used materials, evaluation
applied. All the studies with histological, and D. N.). Titles and abstract screening methods, outcome measures and obser-
radiographic or clinical outcome para- was based on the following questions. vation periods. Additionally, most of
meters evaluating soft tissue and/or bone the studies had either a split-mouth or
healing were included. Only studies pub- a mixed design without providing
lished in English were analyzed.  Was the study conducted on animals
presenting periodontal defects requir- data about intra-individual variance.
ing combined use of barrier mem- Weighted mean differences could not
branes and grafting materials? be calculated, and consequently, it was
Outcome measures determination
 Was treatment outcome evaluated impossible to conduct a quantitative
Primary outcomes of interest were: histologically, radiographically or data synthesis leading to a meta-analy-
clinically? sis. Therefore, the mean and SD, the
 Formation of new periodontal tis-  Was the post-surgery evaluation 95% confidence intervals (CI) and the
sues based on histologic evaluation: period of at least 4 weeks? statistical significance were found and
periodontal ligament, cementum and extracted from the reviewed articles.
bone formation as a linear measure The full text of an article was obtained These data were summarized in separate
(mm) or as a percentage of the whether the response was ‘‘yes’’ or tables based on the different type of
instrumented root length (%). ‘‘uncertain’’ to the screening questions. periodontal defects treated with the
 Change in defect size based on mea- Disagreement regarding inclusion was combined application of barrier
surement after radiographic examina- resolved by discussion. The level of membranes and grafting materials.
tion or re-entry surgical procedure. agreement between reviewers was deter- The defects were classified as follows:
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 Barrier membranes and grafting materials in regenerative periodontal therapy 109

supra-alveolar defects, intrabony defects, Table 2. Paper excluded for clearly not fulfilling inclusion criteria after full-text screening
furcation defects and fenestration defects
Study Reason for exclusion
(Tables 4–7). Furthermore, the results of
the studies that used the same methods of Artzi et al. (2003a) No periodontal defects (bony defects)
evaluation and similar outcome measure- Artzi et al. (2003b) No periodontal defects (bony defects)
ments were combined and the data are Kohles et al. (2000) No periodontal defects (bony defects)
presented in a statistical graph (Fig. 2). Moon et al. (1996) No outcome measurements (descriptive histology)
Ellender et al. (1992) No outcome measurements (descriptive histology)

Results
Data extraction after literature searching
ited an extensive inflammatory reaction restricted from the notch area to the mid
during histological observation and portion of the defect. Fibrous connective
The MEDLINE literature search minimal bone regeneration (Wikesjö et tissue occupied the remaining portion of
resulted in 632 hits (Fig. 1). After the al. 2003). Histomorphometrical para- the defect, whereas epithelial migration
first selection step, based on the title of meters such as extension of long junc- extended to the coronal portion of the
the collected studies, 70 articles were tional epithelium and connective tissue furcation. An inflammatory infiltrate
included for further analysis (inter-reader repair, cementum and bone formation, was also present in all groups. The
agreement k 5 0.96). The hand searching presence of ankylosis and root resorp- amount of periodontal regeneration
revealed 45 articles, which were added to tion were assessed. Limited cementum (periodontal ligament fibres inserting
this step. The second step, based on regeneration was observed in all three into new cementum and new bone) in
abstract screening, resulted in 15 studies studies. Root resorption and ankylosis the three groups was approximately 50%
(inter-reader agreement k 5 0.87). From appeared to be insignificant. A combi- of the root length without differences
these studies, 10 papers completely ful- nation of woven and lamellar new bone between the groups. The root surfaces
filling the inclusion criteria were selected was observed. Bone formation was more were partially covered with new cemen-
(inter-reader agreement k 5 1). Five stu- extensive in the groups receiving the tum of varying thickness. Newly formed
dies were excluded at the last step and combined approach. Particles of the periodontal ligament was present and it
the reasons for exclusion are presented in used biomaterial were surrounded by was highly vascularized. The fibres were
Table 2. The papers that remained after bone and soft tissue and appeared with oriented perpendicular or oblique to the
the third selection (n 5 10) are presented scalloped borders, suggesting active root surface and were inserting into the
in Table 3. resorption. In all groups, connective new cementum and new bone. Areas of
tissue intervened between new bone dentoalveolar ankylosis were also pre-
and instrumented root surface. Addi- sent in some sections, but no active root
Effect of the combined use of GTR and
bone grafts on supra-alveolar defects
tionally, in the groups using either the resorption was observed.
combination approach or the barrier Lekovic & Kenney (1993) evaluated
Three studies related to the periodontal alone, long junctional epithelium was in mongrel dogs four different barriers
regeneration of a supra-alveolar defect absent on the instrumented roots, in conjunction with porous tricalcium
model were identified (Wikesjö et al. whereas in the graft group long junc- phosphate (b-TCP) granules. Histo-
2003, Polimeni et al. 2004, Koo et al. tional epithelium (approximately 10% morphometrical measurements were
2005). The results of the studies are of the root length) was also observed. obtained 6 months postoperatively. All
presented in Table 4. animals had an uneventful healing. The
In all three studies, the supra-alveolar histometric analysis assessed the pre-
Effect of the combined use of GTR and
defects were created by removing sur- bone grafts on furcation defects
sence of root resorption and ankylosis,
rounding bone extending approximately formation of new cementum and bone in
6 mm apical to the cemento-enamel The combination barrier membranes and the furcation area, extent of epithelial
junction of premolar teeth in a canine grafting materials for the treatment of migration, direction of periodontal
model (i.e. Beagle dogs). Cementum furcation defects was evaluated in three fibres and degree of tissue inflammation.
was fully removed by hand and rotating canine studies (Caffesse et al. 1993, The four combined approaches demon-
instruments from the exposed root sur- Lekovic & Kenney 1993, Deliberador strated similar histomorphometric mea-
faces. Non-resorbable ePTFE mem- et al. 2006). The results of these studies surements regarding formation of new
brane (GTR) and coral-derived calcium are presented in Table 5. cementum, new bone and epithelial
carbonate graft were evaluated as treat- Class II furcation defects were either downgrowth. On the other hand, the
ment approaches for periodontal regen- created surgically (Deliberador et al. control group (no material) revealed
eration. Two studies have tested the 2006) or they developed naturally due significantly less cementum and bone
combination (GTR1CI) versus GTR to periodontal disease (Caffesse et al. formation. The inflammatory reaction
alone (Wikesjö et al. 2003, Polimeni et 1993, Lekovic & Kenney 1993). was significantly increased in two
al. 2004) whereas the other study tested Deliberador et al. (2006) evaluated in groups (polycarbonate barrier1b-TCP,
the combination (GTR1CI) versus CI mongrel dogs the following treatments: polycaprolactone barrier1b-TCP) com-
alone (Koo et al. 2005). After a 4-week control, autogenous bone (AB) and pared with the other groups (ePTFE
healing period, clinical observation at combination AB1calcium sulphate barrier1b-TCP, silicone barrier1
sacrifice revealed uneventful healing in paste as barrier (CS). The healing period b-TCP or control), questioning the bio-
all cases. Membrane exposure was not was 3 months. Most specimens failed to compatibility of polycarbonate and
observed. Only one animal, which show complete bone fill of the furcation. polycaprolactone materials. The b-TCP
received the combined approach, exhib- New bone formation was moderate and particles were partially resorbed and
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 110

Table 3. Data extraction from the included studies (n 5 10)

No. Study Year Model Design Animals Defect type Tooth Treatment n Healing Evaluation

1 Koo et al. 2005 Dog Parallel 12 Supra-alveolar Premolar CaC 5 4 weeks histomorphometry
CaC1ePTFE 7 LJE, CT, NC, NB (distance in
mm)
2 Polimeni et al. 2004 Dog Split-mouth 4 Supra-alveolar Premolar ePTFE 4 4 weeks histomorphometry
Sculean et al.

CaC1ePTFE 4 NB (distance in mm)

3 Wikesjö et al. 2003 Dog Split-mouth 5 Supra-alveolar Premolar ePTFE 5 4 weeks histomorphometry
CaC1ePTFE 5 LJE, CT, NC, NB (distance in
mm)
4 Deliberador et al. 2006 Dog Split-mouth 6 Furcation Premolar Control 6 3 months histomorphometry
Class II AB 6 LJE, CT, NC, NB (% of root
length)
AB1CaSB 6
5 Caffesse et al. 1993 Dog Split-mouth 4 Furcation Premolar ePTFE 16 4 months histomorphometry
Class II Molar ePTFE1DFDB 16 LJE, CT, NC, NB (distance in
mm)
6 Lekovic & 1993 Dog Split-mouth 6 Furcation Molar Control 6 6 months histomorphometry
Kenney
Class II ePTFE1CaP 6 NC, NB (distance in mm)
Silrub1CaP 6
PC1CaP 6
PCL1CaP 6
7 Blumenthal et al. 2003 Baboons Split-mouth 9 Intrabony CollB 9 6 months clinical parameters
Three walls DFDB 9 histomorphometry
Two walls DFDB-glyc 9 Periodontal regeneration
(distance in mm)
CollB1DFDB 9
8 Kim et al. 1998 Dog Split-mouth 4 Angular Premolar Control 4 8 weeks histomorphometry
Three walls CaSB 4 LJE, CT, NC, NB (distance in
mm)
DFBM 4
CaSB1DFBM 4
9 Tal et al. 2005 Dog Mixed 12 Fenestration Canine Control 3 3 months histomorphometry
CollB 3 CT, NC, NB (% of defect
height)
BBM 3
BBMC 4
CollB1BBM 3
CollB1BBMC 4
10 Caplanis et al. 1998 Dog Split-mouth 6 Fenestration Canine ePTFE 6 4 weeks histomorphometry
ePTFE1DFDB 6 NC, NB (distance in mm)
Biomaterials: CaC, coral-derived calcium carbonate graft; ePTFE, expanded polytetrafluoroethylene barrier; AB, autogenous bone graft; CaSB, calcium sulfate barrier; DFDB, demineralized freeze-dried bone
graft; CaP, calcium phosphate graft; Silrub, silicone rubber barrier; PC, polycarbonate barrier; PCL, polycaprolactone barrier; CollB, collagen barrier; DFDB-glyc, demineralized freeze-dried bone graft with
glycoprotein; BBM, bovine bone mineral graft; BBMC, bovine bone mineral graft with collagen.
Histological parameters: LJE, long junctional epithelium; CT, connective tissue; NC, new cementum, NB, new bone.

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 Barrier membranes and grafting materials in regenerative periodontal therapy 111

Table 4. Data extraction in the supra-alveolar defect model

Study Design Parameters Distance on the root surface (mm) p value

treatment groups

control graft barrier combination

m (95% CI) m (95% CI) m (95% CI) m (95% CI)

Koo et al. Graft versus Junctional 0.4 (0.1–0.8) 0.0 0.01

(2005) combination epithelium
Connective 4.3 (3.6–5.1) 4.6 (4.1–5.2) 0.44
tissue
Cementum o 0.1 o0.1 0.45
Bone 1.2 (0.1–2.3) 2.3 (1.8–2.9) 0.04
Polimeni et al. Barrier versus Bone 1.3 (0.6–2.1) 2.1 (1.4–2.9) o0.01
(2004) combination
Wikesjö et al. Barrier versus Connective 4.6 (4.0–5.2) 4.5 (3.9–5.1) 0.78
(2003) combination tissue
Cementum 0 0 –
Bone 1.2 (0.5–2.0) 1.9 (1.2–2.6) 0.04
m (95% CI) 5 mean and 95% confidence interval.

Table 5. Data extraction in the furcation defect model

Study Design Parameters Treatment groups p value

control graft barrier combination

m (95% CI) m (95% CI) m (95% CI) m (95% CI)

Percentage of root length (%)

Deliberador et al. Graft versus Junctional 5 ( 4–14) 6 ( 3–14) 10 (0–20) 0.29
(2006) combination epithelium
Control included Connective 35 (16–54) 33 (15–51) 27 (17–37) 0.59
tissue
Cementum 57 (33–81) 59 (40–78) 62 (45–79) 0.85
Bone 62 (53–71) 65 (48- 82) 60 (38–82) 0.69
Distance on the root surface (mm)
Caffesse et al. Barrier versus Junctional 1.6 (0.7–2.5) 1.9 (0.8–3.0) 40.05
(1993) combination epithelium
Connective 1.5 (0.7–2.3) 1.4 (0.4–2.4) 40.05
tissue
Cementum 1.4 (0.6–2.2) 1.0 (0.1–2.0) 40.05
Bone 1.0 (0.3–1.7) 1.1 (0.0–2.3) 40.05
Distance on the root surface (mm)
Lekovic & Kenney 4 different Cementum 0.3 (0.0–0.5) 2.3 (0.7–3.9) o0.05
(1993) combinations
Control included
2.5 (0.9–4.1) o0.01
2.6 (1.0–4.2) o0.01
2.4 (0.7–4.0) o0.05
Bone 0.3 (0.0–0.6) 1.7 (0.6–2.9) o0.01
2.0 (1.0–3.0) o0.01
2.0 (1.0–3.0) o0.01
1.8 (0.9–2.8) o0.01
m (95% CI) 5 mean and 95% confidence interval.

surrounded by new bone. There was no was identical for both treatment groups pied by bone and 30% by connective
evidence of root resorption or ankylosis. (barrier versus combination). New perio- tissue. Epithelial migration was minimal.
Caffesse et al. (1993) compared in dontal fibres were evident including No signs of inflammatory reaction or root
Beagle dogs the use of ePTFE (GTR) cementum deposition and bone regenera- resorption were observed. However, some
barrier versus the combination of tion coronal to the notch. These fibres sections in the graft group demonstrated
GTR1demineralized freeze-dried cortical were oriented perpendicular to the root signs of ankylosis. Both treatments
bone grafts (DFDBA) (GTR1DFDBA). surface and inserted into the new bone resulted in periodontal regeneration but
The animals were sacrificed at 4 months and new cellular cementum. Approxi- adjunctive bone grafting did not appear to
following surgery. The healing pattern mately 70% of the defect area was occu- enhance the regeneration process.
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112 Sculean et al.

Table 6. Data extraction in the intrabony angular defect model

Study Design Parameters Distance on the root surface (mm) p value

treatment groups

control graft barrier combination

m (95% CI) m (95% CI) m (95% CI) m (95% CI)

Blumenthal All treatment Periodontal Non-contained 1.7 (0.9–2.5) 1.3 (0.8–1.8) 1.9 (1.6–2.2) Not mentioned
et al. (2003) modalities regeneration defects:
except control
Contained defects: 1.9 (1.4–2.3) 2.0 (1.3–2.6) 2.2 (1.7–2.7)
Kim et al. All treatment Junctional epithelium 0.9 (0.1–1.7) 0.5 (0.2–0.8) 1.0 (0.2–1.8) 0.6 (0.1–1.1) 40.05
(1998) Modalities Connective tissue 1.6 (0.8–2.4)n 0.4 (0.0–0.9) 0.5 (0.2–0.8) 0.4 (0.0–0.9) n
o0.05
Cementum 1.6 (1.1–2.1)n 3.1 (2.5–3.7) 2.5 (1.9–3.1) 3.0 (2.5–3.5) n
o0.05
Bone 0.7 (0.5–0.9)n 2.7 (2.2–3.2) 1.8 (1.0–2.6) 2.7 (2.1–3.3) n
o0.05
m (95%CI) 5 mean and 95% confidence interval.

Table 7. Data extraction in the angular fenestration defect model

Study Design Parameters Treatment groups p value

control graft barrier combination

m (95% CI) m (95% CI) m (95% CI) m (95% CI)

Percentage of defect height (%)

Tal et al. All treatment Connective 83 69/72 26 33/37 SD, SE or p values
(2005) tissue are not provided
modalities Cementum 17 28/32 84 63/67
Bone 13 39/44 78 81/87
Distance on the root surface (mm)
Caplanis Barrier versus Cementum 1.6 (0.0–3.4) 2.0 (0.6–3.4) 0.39
et al. (1998) combination
Bone 1.5 (0.7–2.3) 0.8 (0.2–1.4) 0.14
m (95% CI) 5 mean and 95% confidence interval.

Effect of the combined use of GTR and with the single therapies. Unfortunately, cementum regeneration and new bone
bone grafts on intrabony defects no p values were provided in the study. formation were calculated. None of the
Periodontal regeneration ranged from sections including DFDBA provided evi-
Two studies providing data on the effect 37% to 48% of the total defect height dence of bone metabolic activity. The
of the use of GTR and graft material in among the groups. Connective tissue use of DFDBA and CS barrier, alone or
intrabony defects were identified (Kim adhesion was also observed. Epithelial in combination, resulted in significantly
et al. 1998, Blumenthal et al. 2003). The migration was limited and encapsulated improved regeneration of alveolar bone
results of these two studies are summar- graft particles were evident. No evi- and cellular cementum in this preclinical
ized in Table 6. dence of inflammation was noticed. model compared with the control group.
In the first study, the authors created The second study has evaluated in However, the barrier alone resulted in
surgically three walled contained and four mongrel dogs the following treat- less bone formation compared with the
two walled non-contained intrabony ment modalities: (a) control (flap alone, groups treated with grafts alone or in the
defects in nine adult baboons (Blu- (b) CS, (c) graft alone (DFDBA) and (d) combination groups. The authors specu-
menthal et al. 2003). Four treatment DFDBA1CS (Kim et al. 1998). Three- lated that space-providing properties of
modalities were tested: (a) GTR alone wall intrabony defects were surgically the materials supported the observed
(i.e. collagen membrane), (b) DFDBA created and subsequently treated with regeneration.
alone, (c) DFDBA/glycoprotein sponge one of the four treatment options. Clin-
and (d) combination of DFDBA1 ical healing was uneventful. Block sec-
collagen membrane. Six months post- tions of the defects were collected at
Effect of the combined use of GTR and
operatively, clinical and histological sacrifice 8 weeks post-operatively and bone grafts on fenestration defects
parameters were evaluated. For the con- processed for histometric analysis. Bone
tained defects, no significant clinical or graft particles were observed clearly Two studies have evaluated in fenestra-
histological differences were found without evidence of residual barrier tion defects the effect of a combination
among the groups. In non-contained particles. Ankylosis was found in three barrier membranes and grafting materi-
defects, the combined therapy (i.e. animals. Connective tissue adhesion als (Caplanis et al. 1998, Tal et al.
graft1GTR) resulted in clinically and (connective tissue contact to the root 2005). In both studies, circular perio-
histologically superior results compared without apparent cementum formation), dontal defects were created by removing
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Journal compilation r 2008 Blackwell Munksgaard
 Barrier membranes and grafting materials in regenerative periodontal therapy 113

alveolar bone, PDL and cementum at Potentially relevant publications

the mid-buccal aspect of canines. identified from electronic search
Caplanis et al. (1998) evaluated the (n = 632)
effect of barrier (ePTFE) against the
Publications excluded on the basis of title
combination of demineralized bone evaluation (n = 562)
matrix (DBM)1ePTFE on fenestration
defects in a dog model. The six dogs
were sacrificed 4 weeks post-surgically Publications added after hand searching on
the basis of title evaluation (n = 45)
in order to assess formation of new
cementum and new bone. Clinical heal- Potentially relevant abstracts retrieved
ing was uneventful and membrane col- for further evaluation
lapse was not observed. DBM particles (n = 115)
were surrounded by connective tissue. Publications excluded on the basis of abstract
No evidence of metabolic activity asso- evaluation (n = 100)
ciated with the graft particles was
observed. Connective tissue was in con- Potentially relevant full-text articles
retrieved for more detailed evaluation
tact with the instrumented root surfaces
(n = 15)
in the absence of cementum formation.
Areas of perpendicular fibre insertion to Publications excluded on the basis of full-
the defected root surface were con- text evaluation(n = 5)
firmed. Ankylosis was not observed. Publications included in the present
Limited and similar amounts of bone systematic review
and regeneration were observed for (n = 10)
both groups.
Tal et al. (2005) used 12 mongrel Fig. 1. Flow-chart of the screening of the relevant publications
dogs and six treatment modalities were
applied including collagen barrier alone,
bovine bone mineral (BBM) alone, % REG
bovine bone mineral collagen study nr 10
combination

(BBMC), collagen barrier1BBM, col- study nr 9b

lagen barrier plus BBMC and control study nr 9a
study nr 8
(i.e. flap alone). Three months post- study nr 7
operatively, histological sections were study nr 5
prepared and new bone, new cementum study nr 4
study nr 9
barrier

and connective tissue adhesion were study nr 8

calculated as percentage of the defect study nr 7
height. The authors did not provide any study nr 5
study nr 10
data about SD, SE or p values in each study nr 9b
group; thus, further analysis is impossi- study nr 9a
graft

ble. However, the use of barrier alone study nr 8

study nr 7b
achieved higher mean values regarding study nr 7a
new bone and new cementum compared study nr 4
control

with all the other groups. The control study nr 9

study nr 8
group demonstrated the lowest values. study nr 4
The authors concluded that the presence
of the collagen barrier was the predo- 0 20 40 60 80 100
minant factor influencing bone and Fig. 2. Mean values of periodontal regeneration (new cementum with inserting periodontal
cementum regeneration. ligament fibres and new bone) were calculated as percentage of the instrumented root length.
Study numeration is described in Table 3.
Data synthesis

Studies using the same methods of eva- demonstrated periodontal regeneration barrier membranes and grafting materi-
luation and similar outcome measure- ranging from 22% to 67% of the instru- als and to address a specific question,
ments were combined and the data are mented root length whereas the groups i.e. whether the preclinical evidence (i.e.
presented in statistical graph (Fig. 2). graft and membrane alone reported 28– data from animal studies) supports the
The mean values of periodontal regen- 63% and 24–78%, respectively. use of such combinations in regenera-
eration (new cementum with inserting tive periodontal therapy. The review
periodontal ligament fibres and new has evaluated the available data from
bone) were calculated as percentage of four different types of experimental
the instrumented root length based on Discussion models (i.e. supraalveolar, Class II fur-
relevant data (distance of new perio- The present systematic review has cation, intrabony and fenestration
dontal tissues divided by the root attempted to provide a biological foun- defects) regarding the effects of various
length). The combined approach dation for the use of combinations of types of barrier membranes and grafting
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Journal compilation r 2008 Blackwell Munksgaard
114 Sculean et al.

materials on the histologic healing. The inflammatory cells following implanta- There was a substantial heterogeneity
results indicate that, independent of tion of resorbable polycarbonate and in the collected data regarding animal
defect type and animal model, regenera- polycaprolactone barriers compared type (i.e. dog or baboon model), study
tive periodontal surgery using combina- with controls (i.e. flap surgery alone) design (i.e. parallel, split mouth or
tions of barrier membranes and grafting or with non-bioresorbable membranes mixed), used materials (i.e. resorbable
materials may result in periodontal made of polytetrafluoroethylene or sili- and non-resorbable membranes, several
regeneration to a varying extent (Caf- cone rubber (Lekovic et al. 1993). grafts such as autograft, allograft xeno-
fesse et al. 1993, Lekovic & Kenney There were only three studies also graft or alloplastic materials), defect and
1993, Caplanis et al. 1998, Kim et al. including open flap debridement as con- tooth type, outcome measures and
1998, Blumenthal et al. 2003, Wikesjö trol (Lekovic et al. 1993, Kim et al. observation periods (from 4 weeks to 6
et al. 2003, Polimeni et al. 2004, Koo 1998, Deliberador et al. 2006). In all months). Additionally, most of the stu-
et al. 2005, Tal et al. 2005, Deliberador three studies, healing following flap dies had either a split-mouth or a mixed
et al. 2006). All evaluated grafting mate- surgery alone was characterized by design without providing data about
rials (i.e. AB, DBM, DFDBA, BBM, incomplete defect fill and limited intra-individual variance. Therefore,
BBMC, b-TCP and CI) appeared to be cementum and bone regeneration. This the combination of the data for a meta-
biocompatible and there were no adverse finding seems to indicate that flap sur- analysis approach was impossible.
effects such as allergies or other immu- gery alone has only a limited effect in Animal research and its value to
nologic reactions, abscess formation or promoting periodontal regeneration. human experience remains controversial
rejection of the grafting materials Superior histologic outcomes, predo- (Weinberg & Bral 1999). It seems
reported. The bone metabolic activity of minantly bone repair, following the use impossible to expect different species
DBM and DFDBA appeared to be lim- of a combination of grafting materials to respond identically or even similarly
ited and was observed in two (i.e. Caf- and barrier membranes compared with to the same challenge except within very
fesse et al. 1993, Blumenthal et al. 2003) grafting materials alone or barrier mem- narrow limits. However, animal data can
out of the four studies using these mate- branes alone were only found in non provide adequate models of biologic
rials in combination with barrier mem- contained periodontal defects (i.e. trends before proceeding to human
branes (Caffesse et al. 1993, Caplanis intrabony defect with missing buccal application. Features of periodontal dis-
et al. 1998, Kim et al. 1998, Blumenthal wall or supraalveolar defects). However, eases in humans and animals vary
et al. 2003). Signs of ankylosis were in contained defects (i.e. fenestration greatly depending on which form of the
observed in one study evaluating treat- defects, three-wall intrabony defects or disease is present and the stage of the
ment of Class II furcation defects with Class II furcation defects) no additional development (Weinberg & Bral 1999).
membrane barriers and DFDBA while no advantage of a combination of grafting Although periodontal defects can be
ankylosis was observed following treat- materials and barrier membranes com- experimentally or surgically induced in
ment with membrane barriers alone (Caf- pared with grafting materials alone or most mammalian species, it is important
fesse et al. 1993). In another study, some barrier membranes alone was found. to choose a laboratory animal model that
of the DFDBA graft particles exhibited Taken together, these histologic findings has similar characteristics of human anat-
mineralization-osteoid formation, indi- seem to support the results of some omy and periodontal disease. Monkey
cating possible osteoinduction (Blu- clinical studies where treatment of and dog models seem to respond
menthal et al. 2003). However, other intrabony defects with a complicated, comparably to humans regarding the
DFDBA graft particles were encapsu- non contained morphology with a com- treatment of periodontal defects (Caton
lated either in connective tissue or bination of barrier membranes and graft- et al. 1994, Weinberg & Bral 1999).
incorporated into new alveolar bone ing materials resulted in superior Furthermore, it appears that the use of
(Blumenthal et al. 2003) while in two clinical outcomes compared with treat- discriminating animal models such as
studies (Caplanis et al. 1998 and Kim ment with barrier membranes alone the critical-size supraalveolar perio-
et al. 1998) DBM particles were found to (Blumenthal & Steinberg 1990, Paolan- dontal defect model appears to provide
be embedded in dense connective tissue tonio 2002). Furthermore, the sugges- important information on the biologic
without evidence of bone metabolic tion that the principal mechanism potential and safety of novel regenerative
activity. Thus, it appears that the osteoin- by which a grafting material may sup- therapies. It was thus suggested that
ductive capacity of DFDBA or DBM port regeneration appears rather to be preclinical research should use such
is highly variable probably due to related to its space-provision capacity discriminating animal models before
differences in methods of harvesting, than to the osteoconductive properties starting clinical evaluation (Polimeni
processing and sterilizing (Schwartz needs to be addressed in further precli- et al. 2006).
et al. 1996). nical and clinical studies (Kim et al. In conclusion, within its limits, the
Generally, the use of barrier mem- 1998, Polimeni et al. 2004, Koo et al. present analysis indicates that:
branes, grafting materials or a combina- 2005).
tion of barrier membranes and grafting It also needs to be pointed out that
materials did not seem to induce anky- most of the studies did not report ade- (a) The combination of barrier mem-
losis or root resorption. A common quate method of randomization to avoid branes and grafting materials may
histologic feature was the limited selection bias. It was also unclear how result in histological evidence of
inflammatory reaction following the the selected studies included allocation periodontal regeneration, predomi-
use of different types of barrier mem- concealment, examiner blinding and nantly bone repair.
branes, grafting materials or combina- operator blinding to minimize the per- (b) No additional benefits of combina-
tions thereof. There was only one study formance and measurements bias (Nee- tion treatments were detected in
reporting increased numbers of chronic dleman 2002). models of three wall intrabony,
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Journal compilation r 2008 Blackwell Munksgaard
 Barrier membranes and grafting materials in regenerative periodontal therapy 115

Class II furcation or fenestration four regenerative procedures. Journal of enhances bone formation in sites implanted
defects. Clinical Periodontology 7, 224–231. with a coral-derived calcium carbonate bio-
(c) In supra-alveolar and two wall Chen, C. C., Wand, H. L., Smith, F., Glickman, material. Journal of Clinical Periodontology
intrabony (missing buccal wall) G. M., Shyr, Y. & O‘Neal, R. B. (1995) 32, 104–110.
Evaluation of a collagen membrane with Lekovic, V. & Kenney, E. B. (1993) Guided
defect models of periodontal regen-
and without bone grafts in treating perio- tissue regeneration using calcium phosphate
eration, the additional use of a graft- dontal intrabony defects. Journal of Perio- implants together with 4 different mem-
ing material gave superior dontology 66, 838–847. branes. A study on furcations in dogs. Jour-
histological results of bone repair to Deliberador, T. M., Nagata, M. J. H., Furlaneto, nal of Periodontology 64, 1154–1156.
barrier membranes alone. F. A. C., Melo, L. G. N., Okamoto, T., Lindhe, J., Nyman, S. & Karring, T. (1984)
(d) In one study using a supra-alveolar Sundefeld, M. L. M. M. & Fucini, S. E. Connective tissue reatachment as related to
model, combined graft and barrier (2006) Autogenous bone graft with or with- presence or absence of alveolar bone. Journal
membrane gave a superior result to out a calcium sulfate barrier in the treatment of Clinical Periodontology 11, 33–40.
graft alone. of Class II furcation defects: a histologic and Löe, H. & Waerhaug, J. (1961) Experimental
histometric study in dogs. Journal of Perio- replantation of teeth in dogs and monkeys.
dontology 77, 780–789. Archives of Oral Biology 3, 176–184.
Ellender, G., Hammond, R., Papli, R., Mitran- Melcher, A. H. (1976) On the repair potential of
gas, K., Bateman, J. F., Glattauer, V., Thyer, periodontal tissues. Journal of Perio-
J. M., Werkmeister, J. A. & Ramshaw, J. A. dontology 47, 256–260.
References (1992) Osteogenic capacity of collagen in Mellado, J. R., Salkin, L.M, Freedman, A. L. &
repair of established periodontal defects. Stein, M. D. (1995) A comparative study of
Artzi, Z., Givol, N., Rohrer, M. D., Nemcovsky, Clinical Materials 9, 201–209. ePTFE membranes with and without decalci-
C. E., Prasad, H. S. & Tal H. (2003a) Gottlow, J., Nyman, S., Karring, T. & Lindhe, J. fied freeze-dried bone allografts for the
Qualitative and quantitative expression of (1984) New attachment formation as a result regeneration of interproximal intraosseous
bovine bone mineral in experimental bone of controlled tissue regeneration. Journal of defects. Journal of Periodontology 66, 751–
defects. Part 1: description of a dog model Clinical Periodontology 11, 494–503. 755.
and histological observations. Journal of Gouldin, A., Fayad, S. & Mellonig, J. (1996) Moon, I. S., Chai, J. K., Cho, K. S., Wikesjö, U.
Periodontology 74, 1143–1152. Evaluation of guided tissue regeneration in M. & Kim, C. K. (1996) Effects of poly-
Artzi, Z., Givol, N., Rohrer, M. D., Nemcovsky, interproximal defects. II. Membrane and glactin mesh combined with resorbable
C. E., Prasad, H. S. & Tal H. (2003b) bone versus membrane alone. Journal of calcium carbonate or replamineform hydro-
Qualitative and quantitative expression of Clinical Periodontology 23, 485–491. xyapatite on periodontal repair in dogs.
bovine bone mineral in experimental bone Haney, J. M., Nilvéus, R. E., McMillan, P. J. & Journal of Clinical Periodontology 23,
defects. Part 2: morphometric analysis. Jour- Wikesjö, U. M. E. (1993) Periodontal repair 945–951.
nal of Periodontology 74, 1153–1160. in dogs: expanded polytetrafluoroethylene Murphy, K. G. & Gunsolley, J. C. (2003)
Blumenthal, N. & Steinberg, J. (1990) The use barrier membranes support wound stabiliza- Guided tissue regeneration for the treatment
of collagen membrane barriers in conjunction tion and enhance bone regeneration. Journal of periodontal intrabony and furcation
with combined demineralized bone-collagen of Periodontology 64, 833–890. defects: a systematic review. Annals of Perio-
gel implants in human infrabony defects. Isidor, F., Karring, T., Nyman, S. & Lindhe, J. dontology 8, 266–302.
Journal of Periodontology 61, 319–327. (1985) New attachment-reattachment follow- Needleman, I. G. (2002) A guide to systematic
Blumenthal, N. M., Alves, M. A. E. F., Al- ing reconstructive periodontal surgery. Jour- reviews. Journal of Clinical Periodontology
Huwais, S., Hofbauer, A. M. & Koperski, R. nal of Clinical Periodontology 12, 728–735. 29 (Suppl. 3), 6–9.
D. (2003) Defect-determined regenerative Karring, T., Isidor, F., Nyman, S. & Lindhe, J. Nygaard-Østby, P., Bakke, V., Nesdal, O.,
options for treating periodontal intrabony (1985) New attachment formation on teeth Nilssen, H. K., Susin, C. & Wikesjö, U. M.
defects in baboons. Journal of Perio- with a reduced but healthy periodontal liga- (2008) Periodontal healing following recon-
dontology 74, 10–24. ment. Journal of Clinical Periodontology 12, structive surgery: effect of guided tissue
Brunsvold, M. A. & Mellonig, J. T. (1993) Bone 51–60. regeneration using a bioresorbable barrier
grafts and periodontal regeneration. Perio- Karring, T., Nyman, S. & Lindhe, J. (1980) device when combined with autogenous
dontology 2000 1, 80–91. Healing following implantation of perio- bone grafting. A randomized controlled clin-
Caffesse, R. G., Nasjleti, C. E., Plotzke, A. E., dontitis affected roots into bone tissue. Jour- ical trial. Journal of Clinical Periodontology
Anderson, G. B. & Morrison, E. C. (1993) nal of Clinical Periodontology 7, 96–105. 35, 37–43.
Guided tissue regeneration and bone grafts in Karring, T., Nyman, S., Lindhe, J. & Siriat, M. Nyman, S., Gottlow, J., Karring, T. & Lindhe, J.
the treatment of furcation defects. Journal of (1984) Potentials for root resorbtion during (1982) The regenerative potential of the
Periodontology 64, 1145–1153. periodontal wound healing. Journal of Clin- periodontal ligament. An experimental study
Caplanis, N., Lee, M. B., Zimmerman, G. J., ical Periodontology 11, 41–52. in the monkey. Journal of Clinical Perio-
Selvig, K. A. & Wikesjö, U. M. E. (1998) Kim, C. K., Kim, H. Y., Chai, J. K., Cho, K. S., dontology 9, 257–265.
Effect of allogenic freeze-dried deminera- Moon, I. S., Choi, S. H., Sottosanti, J. S. & Nyman, S., Karring, T., Lindhe, J. & Plantén, S.
lized bone matrix on guided tissue regenera- Wikesjö, U. M. E. (1998) Effect of a calcium (1980) Healing following implantation of
tion in dogs. Journal of Periodontology 69, sulfate implant with calcium sulfate barrier periodontitis affected roots into gingival con-
851–856. on periodontal healing in 3-wall intrabony nective tissue. Journal of Clinical Perio-
Caton, J., Mota, L., Gandini, L. & Laskaris, B. defects in dogs. Journal of Periodontology dontology 7, 349–401.
(1994) Non-human primate models for test- 69, 982–988. Paolantonio, M. (2002) Combined regenerative
ing the efficacy and safety of periodontal Kohles, S. S., Vernino, A. R., Clagett, J. A., technique in human intrabony defects by
regeneration procedures. Journal of Perio- Yang, J. C., Severson, S. & Holt, R. A. (2000) collagen membranes and anorganic bovine
dontology 65, 1143–1150. A morphometric evaluation of allograft bone. A controlled clinical study. Journal of
Caton, J. G. & Greenstein, G. G. (1993) Factors matrix combinations in the treatment of oss- Periodontology 73, 158–166.
related to periodontal regeneration. Perio- eous defects in a baboon model. Calcified Polimeni, G., Koo, K. T., Qahash, M., Xiropai-
dontology 2000 1, 9–15. Tissue International 67, 156–162. dis, A. V., Albandar, J. M. & Wikesjö,
Caton, J., Nyman, S. & Zander, H. (1980) Koo, K. T., Polimeni, G., Qahash, M., Kim, C. U. M. E. (2004) Prognostic factors for alveo-
Histometric evaluation of periodontal sur- K. & Wikesjö, U. M. E. (2005) Periodontal lar regeneration: effect of a space-providing
gery. II. Connective tissue attachment after repair in dogs: guided tissue regeneration biomaterial on guided tissue regeneration.
r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
116 Sculean et al.

Journal of Clinical Periodontology 31, tion defects in the canine. The International in dogs: a bioabsorbable calcium carbonate
725–729. Journal of Periodontics & Restorative Den- coral implant enhances space provision for
Polimeni, G., Xiropaidis, A. V. & Wikesjö, U. tistry 25, 509–518. alveolar bone regeneration in conjunction
M. E. (2006) Biology and principles of Trejo, P. M., Weltman, R. & Caffesse, R. with guided tissue regeneration. Journal of
periodontal wound healing/regeneration. (2000) Treatment of intraosseous defects Periodontology 74, 957–964.
Periodontology 2000 41, 30–47. with bioabsorbable barriers alone or in com- Wikesjö, U. M. E. & Nilvéus, R. (1990) Perio-
Reynolds, M. A., Aichelmann-Reidy, M. E., bination with decalcified freeze-dried bone dontal repair in dogs: effect of wound
Branch-Mays, G. L. & Gunsolley, J. C. allograft: a randomized controlled clinical stabilization on healing. Journal of Perio-
(2003) The efficacy of bone replacement trial. Journal of Periodontology 71, dontology 61, 719–724.
grafts in the treatment of periodontal osseous 1852–1861.
defects. A systematic review. Annals of Trombelli, L., Heitz-Mayfield, L., Needleman,
Periodontology 8, 227–265. I., Moles, D. & Scabbia, A. (2002) A sys-
Schwartz, Z., Mellonig, J. T., Carnes, D. L. J. tematic review of graft materials and biolo- Address:
R., De la Fontaine, J., Cochran, D.L, Dean, D. gical agents for periodontal intraosseous Anton Sculean
D. & Boyan, B. D. (1996) Ability of com- defects. Journal of Clinical Periodontology Department of Periodontology
mercial demineralized freezed-dried bone 29 (Suppl. 3), 117–135. Radboud University Medical Center
allograft to induce new bone formation. Weinberg, M. A. & Bral, M. (1999) Laboratory P.O. Box 9101
Journal of Periodontology 67, 918–926. animal models in periodontology. Journal of Internal Postal Code 117
Tal, H., Artzi, Z., Moses, O., Nemcovsky, C. & Clinical Periodontology 26, 335–340. 6500 Nijmegen
Kozlovsky, A. (2005) Guided periodontal Wikesjö, U. M. E., Lim, W. H., Razi, S. S., Philips van Leydenlaan 25
regeneration using bilayered collagen mem- Sigurdsson, T. J., Lee, M. B., Tatakis, D. N. The Netherlands
branes and bovine bone mineral in fenestra- & Hardwick, W. R. (2003) Periodontal repair E-mail: [email protected]

Clinical Relevance Principal findings: Most studies have obtained in non-contained two wall
Scientific rationale for the study: A demonstrated periodontal regeneration intrabony and supraalveolar defects.
systematic review of preclinical ani- following the combination of barrier Practical implications: A defect
mal studies was conducted in order membranes and grafting materials. morphology-directed rationale may
to evaluate the effectiveness of a Superior histologic healing following be of importance when a combina-
combination of barrier membranes the combined technique when com- tion of barrier membranes and graft-
and grafting materials on periodontal pared with barrier membranes alone ing materials is considered for
regeneration. or grafting materials alone was only regenerative periodontal therapy.

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard