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Adjuntive Benefit of A Xenogenic Collagen Matrix Associated With Coronally Advanced Flap
Adjuntive Benefit of A Xenogenic Collagen Matrix Associated With Coronally Advanced Flap
DOI: 10.1111/jcpe.13168
CLINICAL PERIODONTOLOGY
1
Honorary Associate Professor in
Periodontology, UCL Eastman Dental Abstract
Institute, London, UK Aim: To evaluate the superiority of coronally advanced flaps (CAFs) when used in
2
Private Practice, Prato, Italy
combination with a xenogeneic collagen matrix (CMX) for root coverage of multiple
3
Specialist Trainee, UCL Eastman Dental
Institute, London, UK
adjacent gingival recessions.
4
Chair and Honorary Consultant in Materials and Methods: Participants with at least 2 upper adjacent teeth exhibiting
Periodontology, UCL Eastman Dental gingival recession depth ≥2 mm were recruited and randomized to CAF with (test) or
Institute, London, UK
5 without (control) CMX, respectively. Mean and complete root coverage, amount of
Department of Surgery and Translational
Medicine, University of Florence, Florence, keratinized tissue (KTw), gingival thickness (GThick) and patient‐reported outcomes
Italy
(PROMs) were recorded at baseline, 3, 6 and 12 months.
Correspondence Results: Twenty‐four patients providing 61 gingival recessions were analysed. After
Roberto Rotundo, Periodontology Unit, UCL
1 year, gingival recession depth decreased from 2.3 ± 0.7 to 0.3 ± 0.4 mm in the
Eastman Dental Institute, 256 Gray’s Inn
Road, London, UK. CAF + CMX group (2.0 ± 0.8 mm meanRC) and from 2.6 ± 1.0 to 0.6 ± 0.3 mm in
Email: r.rotundo@ucl.ac.uk
the control group (2.0 ± 1.1 mm meanRC). No difference was observed between the
Funding information two groups (p = 0.2023). Nineteen (63%) of the test and 16 (52%) of control defects
The study was financially supported in
part by a grant from Geistlich Pharma AG, showed complete root coverage (p = 0.4919). GThick greatly increased in the test
Switzerland. group (0.5 mm; 0.2–0.8 mm, 95% CI; p = 0.0057). No difference between the two
groups was observed for KTw (p = 0.5668) and PROMs.
Conclusion: At 1 year, CAF + CMX provided similar root coverage to CAF alone, but
a significant increase in gingival thickness.
KEYWORDS
gingiva, gingival recession, humans, Mucograft, randomized controlled trials, smiling
1 | I NTRO D U C TI O N root coverage, there is strong evidence supporting the combination of
this technique with autologous connective tissue graft to achieve com‐
In patients with a sufficient amount (≥2 mm) of keratinized tissue, the plete root coverage (CRC) in gingival recessions without interproximal
coronally advanced flap (CAF) has been shown to be a very effective attachment loss and non‐carious cervical lesions, with long‐term sta‐
treatment of single and multiple recessions in terms of aesthetic re‐ bility (Chambrone et al., 2018; Chambrone & Tatakis, 2015; Graziani et
sults and patients' morbidity (Chambrone et al., 2018; Pini‐Prato et al., al., 2014; Pini Prato, Franceschi, Cortellini, & Chambrone, 2018; Pini
2014). Although CAF is a safe and predictable approach for achieving Prato, Magnani, & Chambrone, 2018; Tonetti & Jepsen, 2014).
J Clin Periodontol. 2019;46:1013–1023. wileyonlinelibrary.com/journal/jcpe © 2019 John Wiley & Sons A/S. | 1013
Published by John Wiley & Sons Ltd
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1014 ROBERTO et al.
2.3.1 | Pre‐surgical phase
2.4 | Postoperative care
All participants underwent a comprehensive periodontal examina‐
tion performed by a single calibrated examiner who recorded gingi‐ Following the procedure, all study participants were in‐
val recession depth, probing pocket depth (PD), Full Mouth Plaque structed to rinse twice daily with chlorhexidine mouth rinse
Score (FMPS) and Full Mouth Bleeding Score (FMBS). Prior to surgi‐ (0.12%) for 3 weeks. No toothbrushing was allowed in the
cal therapy, all patients received detailed dental hygiene instructions treated area for 21 days, and thereafter they were instructed
on correct (not‐traumatic) toothbrushing procedures and a course to use only an ultrasoft toothbrush. Anti‐inflammatory ther‐
of professional dental cleaning (supragingival scaling and polishing). apy (Ibuprofen 600 mg, one before the surgery and one after
6 hr) and additional analgesics were prescribed according to
individual needs, and each patient was instructed to keep re‐
2.3.2 | Surgical procedure
cord on a daily basis of the medications used (number and
A single operator (RR), with more than 20 years of experi‐ dosage) and pain intensity using a dedicated questionnaire.
ence in mucogingival surgery, performed all surgical interven‐ All patients were reviewed after 14 days when all sutures were
tions. According to Zucchelli and De Sanctis (2000), an envelope removed.
|
1016 ROBERTO et al.
(b)
(a)
(c) (d)
(a) (b)
(d)
(c)
6. Probing pocket depth (PD), measured using a periodontal probe be‐ reliable if the intra‐class coefficient of correlation was greater
tween GM and the end of the gingival sulcus than 0.70.
7. Clinical attachment levels (CAL), calculated as PD + Rec depth
8. Keratinized tissue (KTw) width, assessed with the visual and func‐
2.9 | Sample size
tional method by means a probe as a distance between GM and
mucogingival junction (MGJ) The following 2 hypotheses were considered: H0, there was no dif‐
9. Keratinized tissue (KT thick) thickness, measured by the use of a ference in mean recession reduction between CAF + CMX and CAF
needle pierced through the centre of a circular‐shaped silicon alone; H1, there was a difference in mean recession reduction be‐
marker of 3 mm in diameter. The edge of the marker (k‐file tween CAF + CMX and CAF alone.
nr. 10) was positioned at the soft tissue margin providing a The following variables were used in order to calculate the sam‐
distance from the margin of 1.5 mm. The distance between ple size:
the tip of the needle and the silicon marker was assessed by
the use of a magnifying glass and a Dentsply Maillefer sili‐ 1. Endpoint: Normal. Difference in reduction in gingival recession
con stops AO197 was used. In addition, a digital calliper C041 (root coverage) between baseline and 1 year
0–150 mm (Kennon Instruments) with a sensibility of 0.01 mm 2. Clinical important difference (Effect size d): set at 1 mm
was used (Santamaria et al., 2008; da Silva, Joly, Lima, & 3. Assessing variability: From a previous study (Woodyard et al.,
Tatakis, 2004) 2004) describing envelope type CAF procedures for the manage‐
10. Duration of the surgery (in minutes) from the first incision to the ment of multiple recessions, a standard deviation of recession re‐
last suture. duction of 0.93 mm was recorded.
4. Mean number of treated teeth per patient (2.92) was obtained
All periodontal clinical measurements were recorded before the sur‐ from a previously published study (Pini Prato et al., 2010)
gery (baseline) and at each follow‐up visits: 3, 6 and 12 months after 5. Intra‐class correlation coefficient (ICC) of the cluster sites (reces‐
mucogingival surgery. sions nested into patient of 0.35) was derived from a previously
A set of frontal and lateral digital pictures were taken at base‐ published study (Pini Prato et al., 2010)
line, after flap elevation, after material application, after sutur‐ 6. Allocation ratio: 1:1
ing, and at 7 and 14 days, 1, 3, 6 and 12 months post‐op in all 7. Type I error: α = 0.05
participants. 8. Type II error: β = 0.10, corresponding to a Power of 90%
9. Accounting for an estimated 10% drop‐out.
2.7 | Patient‐reported outcomes
The sample size calculation using a formula for cluster design was
A preliminary questionnaire was given at baseline to all patients based on the detection of a 1 mm difference in gingival recession
to assess their aesthetic concerns, discomfort whilst brushing and reduction between study groups (standard deviation of 0.93 mm)
hypersensitivity using a linear scale (0 = no problem to 10 = major (Woodyard et al., 2004) with a two‐side 5% significance level, a power
problem). Following the surgery, all participants were instructed of 90%, a mean number of treated teeth per patient of 2.92, an intra‐
to complete a daily diary for 7 days, to record patient‐reported class correlation coefficient of 0.35, resulting in 12 patients needed per
experience measures (PREMs). In the diary, patients were asked treatment group.
to record post‐surgery sequelae, pain and discomfort, chewing
function, interference with daily activities, use of medications
2.10 | Randomization and allocation concealment
more than the prescription. Diaries were collected 7 days after
surgery. The patients were randomized to one of the two groups:
At the 6 and 12 months of follow‐up visits, two additional ques‐ CAF + CMX (test group) and CAF alone (control) on a 1:1 ratio. The
tionnaires were administered to all patients in order to ascertain randomization code was computer‐generated by an independent
discomfort, chewing function, tooth cleaning procedures, den‐ researcher not involved in any clinical evaluations (MN). A blocked
tal hypersensitivity and aesthetic outcomes following the surgical randomization approach was used: 24 patients were divided into
procedure. 12 patients per treatment group. The centre received 24 sequen‐
tially numbered and sealed opaque envelopes containing the
group allocation. The envelope was opened by the investigator
2.8 | Calibration session
only after flap elevation as above mentioned.
One calibrated examiner (LG) performed all clinical periodontal
measurements. For recession depth and incisal margin‐gingival mar‐
2.11 | Blinding
gin measurements, an intra‐rater agreement study was performed.
A set of 20 recessions were evaluated twice with a two‐hour in‐ The surgeon and the patients were aware of the treatment allocation,
terval between the measurements. The examiner was considered whilst the clinical examiner was masked to the treatment allocation.
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1018 ROBERTO et al.
Excluded (n = 0)
Randomized (n = 24)
Allocation
Allocated to CAF intervention (n = 12) Allocated to XCM intervention (n = 12)
♦ Received allocated intervention (n = 12) ♦ Received allocated intervention (n = 12)
♦ Did not receive allocated intervention (give ♦ Did not receive allocated intervention (give
reasons) (n = 0) reasons) (n = 0)
Follow-Up
Lost to follow-up (give reasons) (n = 0) Lost to follow-up (give reasons) (n = 0)
Discontinued intervention (give reasons) (n = 0) Discontinued intervention (give reasons) (n = 0)
Analysis
Analysed (n = 12) Analysed (n = 12)
♦ Excluded from analysis (give reasons) (n = 0) ♦ Excluded from analysis (give reasons) (n = 0)
mean thickness loss of 0.3 ± 0.7 mm, after 12 months. In detail, A reduced surgical time in the CAF‐alone procedure compared to
1 site (8%) in CAF group and 9 sites (56%) in MG group showed a CAF‐CMX was found (mean difference of 11.2 min, 95% CI from 6.8
thickness increase from ≤1 to >1 mm, 1 year after surgery; on the to 15.7 min, p < 0.0001) (Table 4).
contrary, 9 sites (47%) in CAF group and 3 sites (21%) in MG group
showed a thickness decrease from >1 to ≤1 mm (Table 3).
No statistically significant treatment x covariate interactions were 3.2 | Patient‐reported outcomes and
observed (Table 3). experience measures
No substantial differences in all patient‐reported outcomes (aes‐
TA B L E 1 Baseline descriptive statistics. Mean and standard thetics, brushing discomfort, dental hypersensitivity, post‐surgery
deviation are reported for quantitative variables; frequency sequelae, pain and discomfort, chewing function, interference with
(percentage) is reported for the qualitative variables
daily activities, use of medications) were observed between the
CAF CMX study groups (Table 4).
Variable N = 12 Pat N = 12 Pat
GThick > 1 mm 19 (61%) 14 (47%) of the effectiveness of CMX in achieving greater root coverage, re‐
cession reduction and gain in KT compared to CTG plus CAF. These
KT width mm 3.5 (1.8) 3.3 (1.5)
findings have been recently confirmed by a multicentre RCT (Tonetti
Plaque (%) 0 (0%) 0 (0%)
et al., 2018). In this study, superior short‐term results in treating gin‐
BoP (%) 0 (0%) 2 (7%)
gival recessions compared with CAF alone were reported. In terms
PD mm 1.5 (0.5) 1.5 (0.5)
of patient‐related outcomes, the benefit of using CMX appeared lim‐
CAL mm 4.2 (1.3) 3.8 (0.6)
ited. When considering studies aimed to test the adjunctive effect of
CEJ‐GM mm (Rec) 2.6 (1.0) 2.3 (0.7) 0.5 (0.9) 0.2 (0.4) 0.5 (0.8) 0.3 (0.5) 0.6 (0.3) 0.3 (0.4)
Rec width mm 3.6 (0.7) 3.2 (0.7) 1.0 (1.7) 0.7 (1.2) 1.2 (1.7) 0.8 (1.2) 1.5 (1.7) 0.7 (1.0)
GThick mm 1.5 (0.6) 1.4 (0.7) 1.5 (0.8) 1.4 (0.6) 1.4 (0.6) 1.6 (0.8) 1.2 (0.5) 1.7 (0.7)
KT width mm 3.5 (1.8) 3.3 (1.5) 2.8 (2.1) 3.5 (1.5) 2.6 (1.8) 2.8 (1.0) 2.5 (1.1) 2.7 (1.2)
Plaque (%) 0 (0%) 0 (0%) 1 (3%) 5 (17%) 4 (13%) 5 (17%) 0 (0%) 4 (13%)
BoP (%) 0 (0%) 2 (7%) 0 (0%) 0 (0%) 1 (3%) 1 (3%) 1 (3%) 0 (0%)
PD mm 1.5 (0.5) 1.5 (0.5) 1.1 (0.4) 1.5 (0.8) 1.2 (0.6) 1.5 (0.6) 1.3 (0.5) 1.4 (0.6)
CAL mm 4.2 (1.3) 3.8 (0.6) 1.6 (1.1) 1.8 (0.8) 1.7 (1.0) 1.8 (0.7) 1.9 (1.0) 1.7 (0.6)
CRC (%) 0 (0%) 0 (0%) 22 (71%) 22 (73%) 20 (65%) 20 (67%) 16 (52%) 19 (63%)
1020 | ROBERTO et al.
CMX to CAF alone, the review included only two studies at unclear (Jepsen, Stefanini, Sanz, Zucchelli, & Jepsen, 2017). In the present
risk of bias: one performed on localized recessions (Jepsen et al., study despite greater estimates of CRC were observed, a worsening
2013) and the other on multiple recessions (Cardaropoli et al., 2014). trend of the clinical results obtained was however noted between 6
The overall meta‐analysis showed no differences between CMX and and 12 months especially in the control group although this differ‐
CAF in the percentage of complete root coverage (RR 0.86; 95% CI ence resulted statistically not significant. This could be attributed to
0.66–1.11; p = 0.24), even though CMX showed a higher mean per‐ the different flap design (single vs. multiple) used and possibly due
centage of root coverage (mean diff. 9.26%; 95% CI 3.55 to 14.97; to different healing phases followed by the two different surgical
p = 0.001), recession reduction (mean diff. 0.35 mm; 95% CI 0.03 to approaches.
0.66; p = 0.03) and gain in KT (mean diff. 0.36 mm; 95% CI 0.04 to This study results are in contrast to the ones observed by
0.69; p = 0.03) when compared to CAF alone. In contrast, the use Cardaropoli et al. (2014). At this stage, it might be difficult to discuss
of CMX was associated with greater gingival thickness (mean diff. these differences as the study reported better clinical outcomes fa‐
0.55 mm; 95% CI 0.39 to 0.70; p < 0.0001) and this was also ob‐ vouring the combined treatment (93.2% mean RC and 72% CRC vs.
served in this trial. 81.5% mean RC and 58% CRC, respectively) after 1‐year follow‐up.
Similar results, but on localized gingival recessions, were reported Long‐term (beyond 1 year) and properly designed randomized and
by Moreira et al. (2016) and in a secondary analysis performed at multicentre studies should be performed to provide a more defin‐
1 year (Stefanini et al., 2016) on patients recruited from a previous itive answer.
study (Jepsen et al., 2013) with an initial 6‐month duration. Authors In terms of gingival thickness, results obtained by the analyses of
suggested stable clinical outcomes over the additional 6 months in the present study are in line with the ones obtained by Cardaropoli
terms of mean root coverage (76.3% for CAF + CMX and 75.0% for et al. (2014) and Stefanini et al. (2016). A significant increase in gin‐
CAF) and complete root coverage (36% for CAF + CMX and 31% for gival thickness using CMX + CAF compared to CAF alone has been
CAF). Further evidence on the stability of the obtained clinical out‐ consistently reported. It should be noted that 47% of sites treated
comes after 6‐month and 12‐month year for both procedures was with CAF alone showed a decreased thickness (to <1 mm) 1 year
further reported in a third subgroup analysis after 3‐year follow‐up after surgery, compared to 21% of sites treated with CAF plus MG.
ROBERTO et al. |
1021
Despite the current literature reports a possible negative influence Some limitations of the present study should be performed in‐
of thin phenotype (less than 1mm) on the root coverage outcome cluding the single‐centre design and narrow spectrum of gingival
obtained by means of flap approaches (Baldi et al., 1999; Hwang & recessions included for treatment (a relatively shallow initial mean
Wang, 2006; Jepsen et al., 2018), the present study does not identify recession depth of 2.5 mm). This could impact on the external va‐
such negative influence at 1 year of follow‐up. lidity of the study results. Nevertheless a rigorous study design, ap‐
Disagreement is highlighted in terms of keratinized tissue width propriate sample size and statistical analysis, a single experienced
obtained however between the present and the two previous operator and no loss to follow‐up represent the main strengths of
studies. Indeed whilst the present study showed no difference in this study results.
KT width observed between groups (both test and control treat‐ In conclusions from this study comparing the clinical efficacy of
ments showing a reduction), the other 2 studies, performed on CAF plus CMX versus CAF alone for the treatment of multiple ad‐
multiple and single recessions, a KT width increase was reported jacent gingival recessions, we report that (a) CAF + CMX provided
favouring the use of CMX. Possible mechanisms explaining these similar root coverage to CAF alone after 1 year including similar pa‐
tissue volumetric/phenotypic changes could be due to reduced tient‐reported and clinically assessed outcomes; (b) a significant in‐
blood supply of the flap during the initial healing phase as re‐ crease in gingival thickness was obtained when CMX was combined
ported by Pini Prato et al. (2011, 2012). Further research using to CAF. CMX could represent a valid and predictable tool for cli‐
better and more objective tools to monitor soft tissue healing nician when dealing with gingival deformities and thin phenotypes.
should be performed.
With regard to patient‐reported outcomes, evidence from
C O N FL I C T O F I N T E R E S T
the present study suggests no difference in terms of aesthet‐
ics, brushing discomfort, dental hypersensitivity, post‐surgery This research was conducted by the investigators who indepen‐
sequelae, pain and discomfort, chewing function, interference dently performed all phases of the study including protocol develop‐
with daily activities, use of medications between patients who ment, experimental procedures, data analysis, result interpretation
underwent a CAF + CMX versus CAF‐alone procedure. These and reporting.
results confirm the ones observed after treatment of single re‐
cessions by Stefanini et al. (2016). To the best of our knowledge, ORCID
no other evidence is available, and hence, it would be sensible
Roberto Rotundo https://orcid.org/0000-0001-9090-0624
to include appropriate and sufficient number of PROM measures
in future long‐term clinical studies on multiple gingival recession Francesco D'Aiuto https://orcid.org/0000-0001-8654-935X
treatment. Michele Nieri https://orcid.org/0000-0001-8770-4622
|
1022 ROBERTO et al.
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How to cite this article: Rotundo R, Genzano L, Patel D,
Tonetti, M. S., Cortellini, P., Pellegrini, G., Nieri, M., Bonaccini, D., Allegri,
D'Aiuto F, Nieri M. Adjunctive benefit of a xenogenic collagen
M., … Zuhr, O. (2018). Xenogenic collagen matrix or autologous
connective tissue graft as adjunct to coronally advanced flaps for matrix associated with coronally advanced flap for the
coverage of multiple adjacent gingival recession: Randomized trial treatment of multiple gingival recessions: A superiority,
assessing non‐inferiority in root coverage and superiority in oral assessor‐blind, randomized clinical trial. J Clin Periodontol.
health‐related quality of life. Journal of Clinical Periodontology, 45,
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Tonetti, M. S., & Jepsen, S. (2014). Clinical efficacy of periodontal
plastic surgery procedures: Consensus report of Group 2 of the
10th European Workshop on Periodontology. Journal of Clinical
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