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PERIODONTOLOGY 2000
ISSN 0906-6713
104
Clinical evidence
The year 1982 was the starting-point of guided tissue
regeneration (73). Following the first case published
by Sture Nyman, other authors (7, 22, 45, 76) reported encouraging results in independent case
series. That evidence, in fact, demonstrated that applying guided tissue regeneration to deep intrabony
defects could promote significant clinical improvements in terms of clinical attachment and bone
gains and reducing pocket depth. These pioneering
experiences have opened the road to a new era of
excitement in the periodontal field. The original excitement, however, was soon followed by a great deal
of frustration, since clinicians found it very difficult
to predictably duplicate the clinical outcomes reported in the cited studies in daily practice. The application of the biological concept of guided tissue
regeneration appeared to be very difficult and
affected by many different unknown variables.
The turning point in the guided tissue regeneration arena was the year 1993, when the clinical outcomes of a group of 40 intrabony defects treated
with non-resorbable expanded polytetrafluoroethylene membranes were analyzed with a multivariate
statistical approach with the aim of isolating the relevant variables that could influence the healing response and the final clinical outcomes of guided
tissue regeneration (23, 31, 32, 85, 89). The results
from the cited studies demonstrated that the variability in clinical outcomes was affected by patient-,
defect- and procedure-associated factors. Understanding the factors determining the clinical outcomes rendered their control, at least in part, possible, allowing remarkable improvements in their extent and predictability (Fig. 1).
At the end of 1997, 35 scientific investigations had
been published and reported 943 intrabony defects
treated with guided tissue regeneration (Table 1) (1,
57, 9, 11, 1619, 21, 24, 26, 27, 2931, 33, 38, 39, 46,
48, 5153, 55, 59, 63, 67, 74, 75, 77, 84, 88). These
studies have addressed the issue of the evaluation of
the extent and predictability of the clinical outcomes
following application of guided tissue regeneration.
The weighted mean of the reported results indicates
gains in clinical attachment of 3.861.69 mm and
residual probing pocket depths of 3.351.19 mm.
Different types of nonresorbable and resorbable
barrier membranes have been used in the cited
studies. Guided tissue regeneration treatment of 351
defects (20 studies) with nonresorbable barrier
membranes resulted in clinical attachment level
gains of 3.71.8 mm; this was similar to the results
105
Table 1. Clinical studies on guided tissue regeneration with nonresorbable and bioresorbable barrier
membranes
Authors
Type of barrier
Expanded polytetrafluoroethylene
Collagen
Probing
attachment gain
SD
Probing pocket
depth at 1 year
SD
4.5
1.7
3.2
10
0.6
0.6
Expanded polytetrafluoroethylene
1.4
3.9
1.4
Collagen
26
1.5
2.19
0.44
Expanded polytetrafluoroethylene
26
0.8
1.3
5.4
Expanded polytetrafluoroethylene
1.2
1.3
3.5
0.88
Expanded polytetrafluoroethylene
13
1.1
5.1
0.9
Expanded polytetrafluoroethylene
32
4.5
3.88
0.26
Expanded polytetrafluoroethylene
40
4.1
2.5
0.6
Polymer
25
4.5
1.6
1.1
Polymer
47
Rubber dam
Expanded polytetrafluoroethylene
Titanium-reinforced expanded
polytetrafluoroethylene
Collagen
19
3.9
Expanded polytetrafluoroethylene
Expanded polytetrafluoroethylene
14
14
Collagen
Collagen
4.9
2.4
1.4
0.7
2.4
0.5
4.1
5.3
1.9
2.2
2.7
2.1
1
0.5
5
3.7
2.1
2.1
2.6
3.2
0.9
1.8
13
9
2.5
2.4
1.5
2.1
3.6
4
0.6
1.1
Expanded polytetrafluoroethylene
Expanded polytetrafluoroethylene
11
11
4.5
3.3
3.3
1.9
1.7
1.9
Expanded polytetrafluoroethylene
11
0.9
Collagen
10
0.4
4.2
0.4
Expanded polytetrafluoroethylene
Polymer
12
12
5.2
4.6
1.4
1.2
2.9
3.3
0.9
0.9
Expanded polytetrafluoroethylene
23
5.3
1.7
2.7
Polymer
30
2.9
3.6
1.3
Expanded polytetrafluoroethylene
19
2.1
3.2
1.1
Expanded polytetrafluoroethylene
25
2.2
1.4
3.5
1.3
Murphy (67)
Expanded polytetrafluoroethylene
12
4.7
1.4
2.9
0.8
Polymer
10
4.5
0.9
3.1
0.7
Polymer
203
4.8
1.5
3.4
1.6
Polymer
Expanded polytetrafluoroethylene
6
6
2.3
3
2
1.2
3.8
3.7
1.2
1.2
Expanded polytetrafluoroethylene
10
3.7
3.1
1.4
Collagen
52
3.6
2.2
3.9
1.7
Expanded polytetrafluoroethylene
Polymer
10
10
4.3
4.9
1.2
1
3.6
3.9
1.1
1.1
Polymer
18
4.9
1.8
3.6
1.2
Polymer
69
1.6
4.3
1.3
Polymer
Weighted mean
dence interval 3.03.7 mm), while the access flap resulted in a mean gain of 1.81.4 mm (95% confidence interval 1.52.1 mm). The analysis of the reported clinical outcomes strongly suggests an added
benefit deriving from the placement of barrier mem-
106
5
15
15
23
943
2.5
1.7
0.9
3.86
1.69
3.35
1.19
branes after elevation of an access flap. This impression is reinforced by the lack of overlap observed
in the 95% confidence intervals.
The data reported in some of the studies summarized in Table 1 (651 defects in 17 investigations (9,
Table 2. Controlled clinical trials comparing guided tissue regeneration procedure with access flap procedures
Authors
Type of membrane
Guided tissue
n (guided
regeneration
tissue
probing attachment
regeneration) gainSD (mm)
n (flap)
Flap probing
attachment
gainSD (mm)
0.70.9
Collagen
10
0.60.6
10
Collagen
26
3.01.5
26
1.80.9
Expanded polytetrafluoroethylene
1.22.0
0.61.0
Collagen
14
3.9
Collagen
2.42.1
Expanded polytetrafluoroethylene
15
4.11.9
15
Titanium-reinforced expanded
polytetrafluoroethylene
15
5.32.2
Expanded polytetrafluoroethylene
12
5.21.4
12
Polymer
12
4.61.2
Kim (53)
Expanded polytetrafluoroethylene
19
4.02.1
18
2.01.7
Kilic (52)
Expanded polytetrafluoroethylene
10
3.72.0
10
2.12.0
Tonetti (84)
Polymer
69
3.01.6
67
2.21.5
Cortellini (19)
Polymer
23
3.01.7
23
1.61.8
243
3.41.8
213
1.81.4
Weighted mean
14
2.7
0.42.1
2.50.8
2.30.8
* Three-arm studies. Comparisons were made among two different barrier membranes and access flap.
1719, 27, 2931, 33, 38, 39, 48, 55, 59, 75, 84, 88)
allowed a further analysis to address the issue of predictability of obtaining relevant amounts of attachment level gains in intrabony defects. The frequency
distribution of clinical attachment level changes at 1
year has been evaluated subdividing the data in 5
classes of probing attachment level changes: loss of
attachment, gain of 01 mm, gain of 23 mm, gain
of 45 mm and gain of 6 mm or more. Only 2.7% of
651 treated cases lost attachment, while gains of less
than 2 mm were observed in 11% of the cases. Most
of the sites gained considerable attachment. In fact,
gains of 23 mm were observed in 24.8% of the cases,
gains of 45 mm in 41.3%, and gains of 6 mm or
more in 21.2% of defects. These encouraging data
demonstrate that guided tissue regeneration is not
only efficacious, but also predictable.
Five investigations reported changes in bone
levels (7, 32, 48, 51, 78). Bone gains ranged from 1.1
mm to 4.3 mm and seemed to correlate well with
the gains in clinical attachment. The existence of a
correlation between gains in clinical attachment and
gains in bone levels in intrabony defects was demonstrated in an investigation by Tonetti et al. (89). In
this study, the expected position of the bone 1 year
after guided tissue regeneration was consistently
found to be located 1.5 mm apical to the position of
the clinical attachment.
Reduction of pocket depths is one of the critical
107
factors associated with the observed clinical outcomes (58, 8587). These studies have evaluated
three types of possible sources of variability: (i) the
patient; (ii) the morphology of the defect; (iii) the
guided tissue regeneration procedure and the healing period.
The patient
Physiological, environmental, behavioral and genetic patient factors may affect the healing outcome
of guided tissue regeneration procedures. So far, a
highly significant environmental exposure, cigarette
smoking, has been associated with reduced outcomes (86). The ability to maintain high levels of
plaque control has also been associated with improved outcomes (23, 28, 86, 87). Since these factors
can be controlled through behavioral interventions,
clinicians should discuss with the patient the opportunity to further improve hygiene and discontinue
the smoking habit. Another important variable associated with guided tissue regeneration outcomes
is the level of residual periodontal infection in the
dentition, evaluated clinically as the percentage of
sites with bleeding on probing, or microbiologically
as the persistence of periodontal pathogens after
completion of initial therapy (58, 85). A clinical implication of such observation is to defer guided
tissue regeneration procedures until the periodontal
infection is adequately controlled. Despite the lack
of direct evidence, other factors, such as diabetes,
intraoral accessibility and stressful life events,
should be kept in mind in patient selection.
The defect
Defect morphology plays a major role in the healing
response of guided tissue regeneration therapy in intrabony defects. It has been demonstrated that
greater amounts of clinical attachment and bone can
be gained in deeper defects (42, 85, 87). Defects
deeper than 3 mm have been found to result consistently in greater probing attachment gains than defects of 3 mm or less (19). The potential for regeneration, however, has been reported to be similar in
deep and shallow defects. In fact, in the cited study
(19) similar results were observed in shallow and
deep defects, when probing attachment gains were
expressed as a percentage of the baseline intrabony
component of the defects. Another important
morphological characteristic is the width of the intrabony component of the defect, measured as the
angle that the bony wall of the defect forms with the
108
Fig. 6. Conventional technique. The regenerated tissue was not properly protected in the interproximal area.
(36, 37, 69, 70, 77). Antimicrobial prophylaxis of exposed membranes has been shown to be effective in
reducing the bacterial load but ineffective in preventing biofilm formation (40, 69). This evidence
109
The conventional approach consists of a flap approach (access flap or modified Widman flap) not
specifically designed for use with barrier membranes
(7, 22, 31, 48). Full-thickness flaps are elevated to try
to preserve the marginal and the interdental tissues
to the maximum possible extent. Vertical releasing
incisions are performed as needed to increase defect
accessibility. Periosteal incisions are normally performed to allow coronal displacement of the flap and
to improve the ability to cover the membrane. Mattress and passing sutures are placed in the interproximal spaces in order to attempt primary closure
of the interdental tissues over the membranes (Fig.
29).
This approach normally does not allow a complete preservation of the interdental papilla, therefore rendering very difficult the primary closure of
the interdental tissues over the membrane. Major
complications are gingival dehiscence and membrane exposure.
Modified papilla preservation technique
110
Fig. 13. Modified papilla preservation technique. The interproximal defect after debridement.
Fig. 14. Modified papilla preservation technique. A titanium-reinforced barrier membrane was positioned near
to the cementoenamel junction.
Fig. 12. Modified papilla preservation technique. The papilla was elevated along with the full-thickness palatal
flap.
111
112
Fig. 21. Modified papilla preservation technique. After debridement a one- and three-wall combination intrabony
defect was evident.
Fig. 22. Modified papilla preservation technique. A titanium-reinforced barrier membrane was positioned at
the level of the cementoenamel junction.
113
Fig. 26. Modified papilla preservation technique. The regenerated tissue was properly protected with the gingival
flaps.
114
To overcome some of the technical problems encountered with the modified papilla preservation
technique, including difficult application in narrow
interdental spaces and in posterior areas and a suturing technique not appropriate for use with nonsupportive barriers, a different approach, the simplified papilla preservation flap (Fig. 4958), was subsequently developed (30).
This different and simplified approach to the
interdental papilla includes a first incision across the
115
improve the mobility of the buccal flap. After application of a barrier membrane, primary closure of the
interdental tissues above the membrane is
attempted in the absence of tension, with the following sutures: 1) a first horizontal internal mattress suture (offset mattress suture) is positioned in the defect-associated interdental space running from the
base (near the mucogingival junction) of the kera-
Fig. 36, 37. Modified papilla preservation technique. A titanium-reinforced barrier membrane positioned to isolate the defect (buccal and lingual view).
the underlying bone crest. The interproximal papillary tissues at the defect site are gently elevated
along with the lingual/palatal flap to fully expose the
interproximal defect. Following defect debridement
and root planing, vertical releasing incisions and/or
periosteal incisions are performed, when needed, to
116
Fig. 41. Modified papilla preservation technique with bioresorbable membranes. Upper left central incisor at baseline.
Fig. 44. Modified papilla preservation technique with bioresorbable membranes. Primary closure of the interproximal tissues was obtained over the bioresorbable membrane.
Fig. 42. Modified papilla preservation technique with bioresorbable membranes. A deep one-, two- and three- wall
combination defect was evident after debridement.
Fig. 45. Modified papilla preservation technique with bioresorbable membranes. Primary closure was maintained
through time.
Fig. 43. Modified papilla preservation technique with bioresorbable membranes. A bioresorbable barrier was positioned.
Fig. 46. Modified papilla preservation technique with bioresorbable membranes. At one-year, the final fixed reconstruction was placed.
117
Fig. 47. Modified papilla preservation technique with bioresorbable membranes. Baseline radiograph.
Fig. 48. Modified papilla preservation technique with bioresorbable membranes. One-year radiograph.
118
interdental tissues above the membrane are then sutured to obtain primary closure with one of the following approaches: a) one interrupted suture whenever the interproximal space is narrow and the interdental tissues thin; b) two interrupted sutures, when
the interproximal space is wider and the interdental
tissues thicker; c) an internal vertical/oblique mattress suture (25), when the interproximal space is
Fig. 52. Simplified papilla preservation flap. A bioresorbable barrier membrane was positioned to cover the defect.
Fig. 53. Simplified papilla preservation flap. Primary closure of the defect-associated interproximal space. Note
the offset suture positioned on the buccal side of the central incisor.
interproximal bone crest, does not cause any compression at the mid-portion of the membrane, therefore preventing its collapse into the defect. 2) The
119
that these results were obtained by different clinicians treating different populations of patients and
defects including also narrow spaces and posterior
areas of the mouth.
Interdental tissue maintenance
120
Fig. 61. The crestal incision. Filling material was positioned into the defect to support the bioresorbable barrier
membrane.
121
122
Fig. 69. Free gingival graft. The intrabony component of the three-wall defect was 5 mm.
Fig. 70. Free gingival graft. A nonresorbable barrier membrane was positioned.
Fig. 72. Free gingival graft. The regenerated tissue at membrane removal
(week 5) was slightly inflamed.
Fig. 73. Free gingival graft. A saddleshaped free gingival graft was positioned in the interproximal space to
protect the regenerated tissue.
123
generated tissue was afforded with coronal positioning of the gingival flap (3.72.1 mm). In 12 of
the 14 grafted sites the free gingival graft succeeded;
in the other 2 it was lost.
Postoperative regime
124
Barrier membranes
Nonresorbable and bioresorbable barrier membranes are available. The main clinical difference
among the two types is the need of a second surgery
to remove the nonresorbable barrier membranes.
Among the latter, the expanded polytetrafluorethylene membranes are widely used and successfully
tested in many clinical studies (Table 1). The titanium-reinforced membrane is an evolution of the
expanded polytetrafluoroethylene barrier. The design of this barrier enhances its ability to save space
for regeneration and to support the gingival tissues.
In recent years bioresorbable barrier membranes
have been introduced in guided tissue regeneration
to avoid further surgery. Barrier membranes of collagen (Table 1) and of polylactic acid or copolymers of
polylactic acid and polyglycolic acid (Table 1) have
been evaluated in independent studies, with various
degrees of clinical success. From a clinical standpoint, these membranes are generally easy to manipulate and position about the defect, but have a
limited ability to save room for regeneration and to
support the gingival tissues.
A subset analysis performed on the studies listed in
table 1 to compare the 351 sites treated with non-resorbable barriers and the 592 treated with bioresorbable ones shows probing attachment gains of 3.71.8
mm (95% confidence interval 3.4 to 4.0 mm) for the
nonresorbable group and probing attachment gains
of 3.61.5 mm (95% confidence interval 3.4 to 3.8
mm) for the bioresorbable one. When the bioresorbable group is further subdivided into two subgroups,
one for collagen material, the other for polymers, the
weighted mean in terms of probing attachment gain
is 3.01.7 mm (95% confidence interval 2.5 to 3.5
mm) for the 139 collagen-treated sites, and 4.11.6
(95% confidence interval 3.9 to 4.4 mm) for the 453
sites treated with polymers. These data seem to indicate that similar outcomes can be expected using
nonresorbable and bioresorbable barriers. Among the
bioresorbable membranes, however, better outcomes
are to be expected using polymers.
Combination treatment
Schallhorn & McClain have suggested that a combination therapy consisting of barrier membranes plus
bone grafting may result in significant improvements
of expected outcomes (60, 76). Four studies (16, 52, 53,
63), however, evaluating the added benefit of bone or
bone substitutes used in combination with barrier
Complications
Complication of guided tissue regeneration procedures are frequent and frequently associated with
impairment of the clinical outcomes. Membrane exposure has been reported in many investigations to be
the major complication with a prevalence in the range
of 70 to 80% (7, 22, 31, 36, 37, 65, 78). Prevalence of
membrane exposure has been highly reduced with
the use of access flaps (modified papilla preservation
technique, interproximal tissue maintenance and
simplified papilla preservation flap) specifically designed to preserve the interdental tissues (25, 29, 30,
67, 84). Control of membrane exposure is of great importance for the clinical outcomes, since in many
studies exposed membranes have been shown to be
contaminated with bacteria (36, 37, 47, 58, 64, 6870,
77, 79, 83). Contamination of exposed nonresorbable
and resorbable barrier membranes has been associated with reduced probing attachment gains in intrabony defects (36, 37, 69, 70, 77).
Other postoperative complications such as swelling, erythema, suppuration, sloughing or perforation
of the flap, membrane exfoliation and postoperative
pain have been reported in independent studies. An
investigation reported the prevalence of pain (16%
of cases), suppuration (11%), swelling and sloughing
of the marginal portion of the flap (7%) in the immediate postoperative period (65, 66). Postsurgical
pain can be easily controlled with administration of
pain-killers. The events connected with local bacterial contamination are treated by enhancing the
infection control regime both at home and in the
dental office. This is based on the use of chlorhexidine rinses and gels, wiping devices such as soft
toothbrushes and cotton pellets and frequent professional cleaning and prophylaxis. Perforation of
the flap or severe exposure of the membrane could
require removal of the material.
125
Fig. 77. Decision tree 1: selection of patient, defect and objective of treatment.
Treatment strategies
Guided tissue regeneration in the year 2000 can no
longer be considered as a single treatment approach.
In fact, today there is evidence to consider guided
tissue regeneration as a multifactorial treatment approach comprising careful selection of patients and
126
modified papilla preservation technique. ITM: interproximal tissue maintenance. SPPF: simplified papilla preservation flap. e-PTFE: expanded polytetrafluoroethylene.
ability with the minimal degree of technical difficulty, to reach the desirable objective of the treatment.
With this in mind, three operative decision trees,
based on a stepwise approach with subsequent decision nodes, have been built up to assist clinicians
in the process of selecting the proper treatment
strategy in different clinical cases. A first decision
tree (decision tree 1) will help clinicians in selecting
patients, defects and setting the objectives of treatment. Then, two different trees, one for non-aesthetically sensitive sites (decision tree 2) and the other
for aesthetically sensitive sites (decision tree 3), will
help clinicians in selecting the treatment strategy.
The starting-point of the decision process is the
selection of the patient (decision tree 1, node 1; see
paragraph the patient). According to the evidence,
patients with less than 15% of sites presenting with
plaque and residual infection, nonsmokers, with a
high degree of compliance, and systemically healthy
are the best candidates for guided tissue regeneration.
The second step is the selection of the defect (de-
127
128
lene membranes has been reported to result in clinical attachment level gains in the supracrestal portion of the defects (27). When the defect is purely
intrabony, if it is a wide (ample radiographic angle)
and/or a nonsupportive defect (one- and two-wall
configurations), a titanium-reinforced expanded polytetrafluoroethylene membrane is again the first
choice. When the defect is narrow and/or has a supportive anatomy (three-wall configurations), bioresorbable membranes, eventually associated with
supportive materials (bone or bone substitutes), can
be successfully applied.
The suturing approach (node 3) will be chosen according to the defect anatomy and the type of membrane or combination material used in a given case.
A combination of two sutures, one to relieve the tension, the other to close the flap are mandatory. A
supportive defect (three-wall defect), a self-supporting membrane (titanium-reinforced expanded polytetrafluoroethylene membrane) or a supported
membrane (combination therapy) requires suturing
the interdental space with an internal horizontal
crossed mattress suture (25) to relieve the tension. If
a nonsupported membrane (bioresorbable material)
or a nonsupportive defect (one- or two-wall defect)
is the case, an offset internal mattress suture (30) will
be chosen. Primary closure of the interdental space
will be attempted in both the instances with a single
passing suture when the papilla is very narrow; with
two parallel passing sutures when the papilla is
wider; with an internal mattress suture or with an
internal mattress suture (54) to get the best apposition of the flap edges.
When nonresorbable barrier membranes are used
at the time of membrane removal (node 4), the regenerated tissues can be protected with a replacement flap in case of gingival integrity or with a
saddle-shaped free gingival graft in case of gingival
dehiscence (24).
Conclusions
Evidence demonstrates a clear benefit from the use
of barrier membranes in the treatment of intrabony
defects. The clinical outcomes, in terms of gain of
periodontal support, pocket depth reduction and
minimal recession of the gingival margin, are influenced by a series of factors that can be controlled, at
least in part. Control of these factors is of paramount
importance to enhance the predictability of guided
tissue regeneration treatment. Clinicians should
carefully select patients and defects, set the objec-
129
tives of treatment and then design the surgical strategy. Several surgical alternatives and different materials can be variously combined to optimize the
treatment strategy. The decision-making process
should be undertaken while keeping in mind the
ratio between the difficulties of the selected procedures and the expected outcomes. A good balance
between these two components will be the key to
success.
13.
14.
15.
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