RESEARCH
Clinical O al In es iga ions (2024) 28:215
h ps://doi.o g/10.1007/s00784-024-05602-9
In oduc ion
Gingi al ecessions a e a e y common pa hology in he
adul popula ion [1, 2]. The ideal goal o ecession ea men
is o achie e comple e oo co e age (CRC) [3] and good
aes he ic esul s o su ounding so issues [4].
In e ms o he pe cen age o mean oo co e age (MRC)
and CRC, he ea men o choice is he combina ion o a
subepi helial connec i e issue g a (CTG) wi h a co onally
ad anced lap (CAF) [5–7]. The use o a CTG inc eases
gingi al hickness (GT) and achie es long- e m s abil-
i y [8] o he gingi al ma gin [6, 9]. Howe e , ob aining a
CTG may cause pos ope a i e complica ions [10, 11], hus
leading o he de elopmen o di e en al e na i es, such
Ga cía-De-La-Fuen e Ana-Ma ía
[email p o ec ed]
1 Uni e si y o he Basque Coun y (UPV/EHU), Biscay, Spain
2 Resea ch G oup: GIU21/042. Depa men o S oma ology,
Facul y o Medicine and Nu sing, Uni e si y o he Basque
Coun y (UPV/EHU), Ba io Sa iena s/n, Biscay,
Leioa 48940, Spain
3 Resea ch G oup: GIU21/042. Depa men o Nu se y I.
Facul y o Medicine and Nu sing, Uni e si y o he Basque
Coun y (UPV/EHU), Biscay, Spain
4 Resea ch G oup: GIU21/042. Depa men o S oma ology,
Uni e si y o he Basque Coun y (UPV/EHU), Biscay, Spain
Abs ac
Objec i es To compa e he clinical e icacy in e ms o mean oo co e age in RT2 ecession ea ed wi h a co onally
ad anced lap combined wi h a xenogeneic collagen ma ix e sus a connec i e issue g a .
Ma e ials and me hods A o al o 20 pa ien s we e andomized o ecei e one o wo ea men s: co onally ad anced
lap + xenogeneic collagen ma ix ( es g oup) and co onally ad anced lap + connec i e issue g a (con ol g oup). Pa ien -
ela ed ou comes measu es and p o essional aes he ic assessmen by oo es he ic sco e we e pe o med. A desc ip i e and
analy ical s a is ical analysis o he a iables was pe o med.
Resul s A 12 mon hs, he mean oo co e age was 56.48% in he es g oup and 69.72% in he con ol g oup (p = 0.048),
wi h a 35% and 40% comple e oo co e age in he xenogeneic collagen ma ix and connec i e issue g a , espec i ely.
Tes g oup p esen ed less pain (3.65 s. 5.2 VAS uni s) (p = 0.015) and less su gical ime (45 s. 49.15 min) (p = 0.004) han
con ol g oup.
Conclusion The use o xenogeneic collagen ma ix in RT2 ecessions was e ec i e o ecession educ ion o hose ob ained
using au ologous g a s; wi h he ad an age ha he du a ion o su ge y and pa ien mo bidi y dec eased. The e o e, xenoge-
neic collagen ma ix in RT2 ecessions could be an al e na i e o au ologous g a s.
Clinical ele ance The use o xenogeneic collagen ma ix dec eases he su ge y ime and pa ien mo bidi y bu connec i e
issue g a esul s in signi ican ly be e mean oo co e age and comple e oo co e age. Xenogeneic collagen ma ix can
be used in he ea men o RT2 gingi al ecessions.
S udy egis a ion NCT 03344315.
Keywo ds Collagen ma ix · Gingi al ecession · Connec i e issue · Plas ic su ge y p ocedu es · Clinical ial
Recei ed: 8 Decembe 2023 / Accep ed: 5 Ma ch 2024 / Published online: 15 Ma ch 2024
© The Au ho (s) 2024
Analysis o he ea men o RT2 ecessions wi h a xenogeneic collagen
ma ix s. connec i e issue g a combined wi h a co onally ad anced
lap. A double-blinded andomized clinical ial
Ruiz-de-Gopegui-PalaciosElena1· Vilo -Fe nándezMi en1· Ga cía-De-La-Fuen eAna-Ma ía2,4·
Ma ichala -MendíaXabie 3· Agui e-Zo zanoLuis-An onio2
1 3
Clinical O al In es iga ions (2024) 28:215
as memb anes [12], biological agen s [13], and allog a s
[14]. The objec i e o hese he apies was o ind a he apeu-
ic al e na i e o he use o CTGs, hus allowing he ea -
men o mul iple ecessions in a single session, which can
educe su ge y imes, a oid he need o a second su ge y,
and imp o e he colo and ex u e o he issues [12–16].
This is especially impo an in pa ien s wi h pe iodon i is
and mul iple ecessions wi h in e p oximal a achmen loss
whose ea men is mo e complex [17].
The use o a xenogeneic collagen ma ix (CMX)
(Geis lich Mucog a ®: Geis lich Pha ma, AG, Wolhusen
Swi ze land) has been p oposed as an al e na i e ea men
o egene a ion a ound ee h, ob aining p omising esul s in
compa ison wi h CAF alone [6, 18, 19] in achie ing g ea e
oo co e age and ke a inized issue. These s udies ha e
been pe o med in single and mul iple RT1 [20] ecessions
wi h di e en ollow-ups and su gical echniques such as
CAF o Modi ied Ad anced Co onal Tunneling Ad anced
(MCAT) [6, 18, 19]. While he pe cen age o MRC a 12
mon hs wi h MCAT [21, 22] anged om 53.2% [21] o 71%
[22] he combina ion o CMX + CAF [8, 15, 23–26] showed
be e esul s in oo co e age (76.28% [23] − 94.32% [26]).
RT2 [20] ecessions a e e y p e alen in he adul pop-
ula ion [6], bu he CRC is no always p edic able [27].
Al hough he e a e clinical s udies in which CRC as well
as high pe cen ages o MRC ha e been achie ed [28, 29],
i is necessa y o de e mine he p edic abili y o ea men
wi h au ologous g a s as well as wi h possible al e na i e
he apies [6, 30], such as he CMX.
Hence, his mul icen e clinical ial aimed o compa e he
clinical e icacy o CMX (Geis lich Mucog a ®: Geis lich
Pha ma, AG, Wolhusen Swi ze land) e sus a subepi helial
CTG when combined o CAF [31] o he ea men o RT2
ecessions in e ms o pe cen age o MRC.
Ma e ials and me hods
T ial design
This was a andomized, double-blind, mul icen e (2-cen-
e ) clinical ial wi h a 12-mon h ollow-up pe iod. The
s udy was egis e ed in clinical ials.go (NCT 03344315)
and was conduc ed ollowing he Consolida ed S anda ds
o Repo ing T ials (CONSORT) guidelines [32]. The s udy
was conduc ed ollowing he p inciples o he Decla a ion
o Helsinki ( e ised in 2013) and was app o ed by he Eus-
kadi E hics Commi ee (CEIC-E) (PI 20,161,008-PS) in
Feb ua y 2017.
The p ima y aim was o analyze he pe cen age o MRC
associa ed wi h he ea men o ecessions wi h CMX ( es
g oup) s. CTG (con ol g oup), wi h he null hypo hesis
(H0) ha bo h ea men s a e equally e ec i e a 12 mon hs.
The seconda y ou comes we e he pe cen age o CRC,
he educ ion o ecession (REC ed) measu ed in mm, he
gain in ke a inized issue wid h (KTW), he change in GT,
pa ien - ela ed ou come measu es (PROMs) ega ding pos -
su gical pain, sa is ac ion wi h he ea men and aes he ics
pe cei ed by he pa ien , and aes he ics by a blinded clinical
moni o (MVF).
Pa icipan s
Re e ence popula ion
All pa icipan s we e ec ui ed om wo p i a e cen e s
be ween Ma ch 2017 and May 2019. Pa ien s ecei ed
in o ma ion abou he ea men and he ad an ages and dis-
ad an ages o pa icipa ing in his s udy. In o med consen
was ob ained om all pa icipan s be o e he s a o he
s udy.
Inclusion c i e ia we e as ollows: (a) pa ien s ≥18 yea s
old; (b) pe iodon ally ea ed and heal hy wi h a leas one
o mo e RT2 buccal gingi al ecessions in inciso s, canines,
and p emola s, loca ed in he same quad an o sex an wi h
a minimal dep h o ≥ 2 mm; (c) ull mou h plaque index had
o be unde 25% [33].
The exclusion c i e ia we e as ollows: (a) ac i e pe i-
odon al disease; (b) subjec s wi h se e e sys emic pa hology
who ook o had aken medica ion ha could in e e e wi h
he healing o pe iodon al issues du ing he las 6 mon hs.
Sample size calcula ion
Fo sample size calcula ion, he pe cen age o MRC was
conside ed as he p ima y ou come o calcula e he sample
size. To p o ide a s a is ical powe o 80%, an α- isk o 5%,
and an SD = 14, as p e iously desc ibed in he li e a u e
[22], 18 pa ien s would be necessa y. To accoun o an ici-
pa ed d opou s, an addi ional 10% was added, esul ing in
20 pa ien s.
Randomiza ion
To de e mine he ype o g a (CMX o CTG) o be used, he
pa ien s we e andomized in blocks o wo ea men s using
s a is ical so wa e (IBM SPSS® S a is ics 20.0) (AMGF).
The alloca ion was kep hidden by a clinical moni o
(AMGF) un il he ime o he in e en ion in opaque en e-
lopes ha we e opened immedia ely a e lap ele a ion.
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Clinical O al In es iga ions (2024) 28:215
Con ol o s udy bias
The clinical examine (MVF) and he bios a is ician (XMM)
we e blinded o he ype o ea men (CMX o CTG). The
ep oducibili y o he clinical examine (MVF) was de e -
mined by e alua ing 4 pa ien s (p esen ing mul iple RT2
ecessions) no ela ed o he s udy, a leas wice, wi h a
sepa a ion o a leas 24 h. An in aclass co ela ion coe -
icien > 0.85 was conside ed accep able.
In e en ion: Su gical p ocedu e
All pa ien s ini ially comple ed a plaque con ol p og am,
including o al hygiene ins uc ions [34] o co ec hab-
i s ela ed o he e iology as well as a p esu gical p ophy-
laxis. All he su ge ies we e pe o med by wo expe ienced
pe iodon is s (LAAZ and ERGP), being he CAF [31] he
echnique chosen in all cases. The da a ela ed o he chai
ime, de ined as he du a ion o he su gical p ocedu e (in
minu es) om he i s incision o he las su u e was also
egis e ed.
A e p epa ing he ecipien bed, a CMX (Geis lich
Mucog a ®: Geis lich Pha ma, AG, Wolhusen Swi ze land)
( es g oup) o CTG (con ol g oup), which was ob ained
using he UPV/EHU echnique [35], was implan ed. Bo h
he CMX and he CTG we e su u ed wi h abso bable su u es
(E hicon Vic yl® 5/0; Johnson & Johnson); he lap was
su u ed wi h Go e-Tex e-PTFE® 5/0 (W.L. Go e & Associ-
a es (UK), LTD, Sco land))
Pos ope a i e ca e included a single p esu gical dose o
2 ml o in amuscula be ame hasone (Celes one® C ono-
dose®, Sche ing Plough S.A., Spain), amoxicillin 875 mg/
cla ulanic acid 125 mg (Augmen ine®, GlaxoSmi hKline
S.A., Spain) e e y 8 h o 7 days, analgesics on demand
(25 mg dexke op o en) and inses wi h 0.2% chlo hexidine
diglucona e (2 imes a day o 3 weeks). Also, local cold
applica ions o wo days, a so die and no physical exe -
cise du ing he i s week a e he su ge y we e ad ised.
Su u es we e emo ed om he pala e a 7 days and om
he ecipien bed a 14 days espec i ely. A 21 days a e
su ge y, daily b ushing was esumed [34].
Moni o ing and da a collec ion
A 7, 14 days, 4 weeks, 6, and 12 mon hs pa ien s we e
scheduled o a end ollow-up appoin men s, which included
a p o essional plaque emo al wi h ein o cemen o o al
hygiene ins uc ions.
Clinical pa ame e s
A baseline, 6 and 12 mon hs, an expe ienced, blinded, and
p e iously calib a ed examine (MVF) eco ded he ol-
lowing pa ame e s using a s anda dized pe iodon al p obe
(PCP-11, Hu-F iedy, M g. Co. LLC, Chicago, USA); he
measu emen s we e ounded o he nea es 0.5 mm:
●Recession dep h (REC dep h): measu ed in he mid es-
ibula om he cemen o-enamel junc ion (CEJ) o he
deepes poin o he pocke . As non-ca ious ce ical le-
sions we e no excluded, i he CEJ was no p esen o
no de ec able, i was de e mined using he echnique
desc ibed by Cai o and Pini-P a o [36] in 2010.
●Recession wid h (REC wid h): measu ed mesio-dis ally
a he le el o he CEJ.
●Ke a inized issue wid h (KTW): measu ed om he
gingi al ma gin o he mucogingi al junc ion.
●Clinical a achmen le el (CAL), measu ed om he
CEJ o he gingi al ma gin o he deepes poin o he
pocke (PD + REC dep h).
●Pe cen age o CRC ( he numbe o ea ed ecessions
wi h REC dep h = 0 mm): CRC × 100/numbe o
ecessions.
●Pe cen age o MRC (mean p eope a i e REC dep h
-mean pos ope a i e REC dep h/mean p eope a i e
REC dep h × 100) we e calcula ed.
●GT: measu ed 3 mm apical om he cen e o he gingi-
al ma gin (a baseline and 12 mon hs) using a 25-gauge
K endodon ic ile wi h a ubbe s oppe , measu ed pe -
pendicula o he oo h axis unde local anes hesia.
Pa ien - ela ed ou comes measu es
Rega ding es he ics, a PROM was ca ied ou using a isual
analogue scale (VAS, anging om 0 o10) in which pa ien s
we e asked o sco e hei sa is ac ion ela ed o hei clinical
expe ience (p ocedu e and pos ope a i e pain) a 7 days and
es he ic (0 = wo s possible aes he ic esul and 10 = excel-
len aes he ic esul ) a 12 mon hs. Respec ing he clinical
expe ience (0 was conside ed he wo s p ocedu e expe i-
enced o he pa ien and 10 he bes ) and o pos ope a i e
pain (0 = no pain and 10 = ex eme pain).
P o essional es he ic e alua ion
Besides he pa ien ’s es he ic pe cep ion, he es he ics we e
also assessed om a p o essional poin o iew. Thus, one
blinded and calib a ed examine (MVF) compa ed he pho-
og aphs aken a baseline and 12 mon hs pos ope a i ely.
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Clinical O al In es iga ions (2024) 28:215
S udy popula ion
Twen y pa ien s (13 women (65%)) wi h a mean age
o 48.59 yea s (SD:10.32), o whom wo we e smok-
e s (10%) pa icipa ed in his s udy. The 96.39% o
he pa icipan s had mul iple ecessions. A o al o 111
RT2 ecessions we e ea ed (CMX: 58 s. CTG: 53),
among which 65 (CMX: 34 s. CTG: 31) we e in he
mandible (58.5%). A o al o 31 inciso s (27.92%), 36
canines (32.43%), and 44 p emola s (39.63%) we e
included. REC dep h, REC wid h, KTW, GT, and CAL
a baseline a e shown in Table 1.
Clinical esul s
Clinical esul s a 6 mon hs a e summa ized in Table 2.
When analyzing he in e g oup esul s, no signi ican di -
e ences we e obse ed in any o he pa ame e s analyzed.
Clinical esul s a 12 mon hs a e epo ed in Tables 2 and 3,
and 4; he changes be ween 6 and 12 mon hs a e shown in
Table 3.
The pe cen age o MRC was 56.48% on es and
69.72% on con ol si es a 12 mon hs (p = 0.048).
Be ween 6 and 12 mon hs, he pe cen age o MRC
dec eased om 59.60 o 56.48% in he es g oup
The assessmen was made using he Roo Co e age Es he ic
Sco e (RES) [37].
S a is ical analysis
All he ob ained da a we e analyzed using s a is ical so -
wa e (IBM SPSS® S a is ics 20.0; IBM, Chicago, IL,
USA), wi h he pa ien as he uni o analysis. Ini ially, he
Shapi o–Wilk es was used o e alua e i he dis ibu ion
was no mal o no . Fi s , desc ip i e s a is ics we e pe -
o med, and means and s anda d de ia ions we e p o ided
o quan i a i e a iables, and pe cen ages we e de e mined
o ca ego ical a iables. Subsequen ly, in he analysis o
s a is ical ela ionships, no mali y es s led o he use o
nonpa ame ic es s o bo h in ag oup (Wilcoxon es o
he anges o ela ed samples) and in e g oup compa isons
(Mann–Whi ney U).
Resul s
The CONSORT diag am, which shows each g oup and he
numbe o pa icipan s, as well as he numbe o d op-ou s,
is shown in Fig. 1.
Fig. 1 CONSORT diag am
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215 Page 4 o 12
Clinical O al In es iga ions (2024) 28:215
Table 1 Baseline cha ac e is ics o he s udy popula ion
Tes (CMX)
(n = 0)
Con ol (CTG)
(n = 20)
P alue To al
Age (mean ± SD) 48.79 ± 10.35 48.39 ± 10.59 0.73 48.59 ± 10.32
Females n (%) 13 (65%) 13 (65%) > 0.05 13 (65%)
Smoke s n (%) 1 (5%) 1 (5%) 2 (10%)
REC pe pa ien
(mean ± SD) [ ange]
2.9 ± 1.12 [1–5] 2.65 ± 0.99 [1–4] 0.622 2.78 (1.05) [1–5]
REC maxilla n (%) 24 (41.38%) 22 (41.51%) > 0.05 46 (41.44%)
REC mandible n (%) 34 (58.62%) 31 (58.49%) 65 (58.5%)
REC dep h (mm) (mean ± SD)
[ ange]
3.69 ± 1.03
[2.25–5.5]
3.67 ± 0.66
[2.25–4.75]
0.968 3.68 ± 0.85
[2.25–5.5]
REC wid h (mm)
(mean ± SD)
[ ange]
4.15 ± 0.73
[2.75–5.5]
3.91 ± 0.68
[2.5–5.5]
0.289 4.03 ± 0.71
[2.5–5.5]
CAL (mm)
(mean ± SD)
[ ange]
4.88 ± 1.12
[3.33–7]
4.95 ± 0.75
[3.25–6.5]
0.565 4.91 ± 0.95
[3.25–7]
KTW (mm)
(mean ± SD)
[ ange]
1.78 ± 1.24
[0–5]
1.77 ± 1.10
[0–4]
0.968 1.78 ± 1.24
[0–5]
GT (mm)
(mean ± SD)
[ ange]
1.09 ± 0.28
[0.5–2]
1.19 ± 0.29
[1–2]
0.365 1.14 ± 0.29
[0.5–2]
REC dep h (Recession dep h); REC wid h (Recession wid h); KTW (ke a inized issue wid h); CAL (Clinical a achmen le el); GT (Gingi a
hickness); SD (s anda d de ia ion); mm (millime e s); CMX (xenogeneic collagen ma ix); CTG (connec i e issue g a )
Table 2 Clinical esul s a baseline (T0), six (T1) and wel e (T2) mon hs
G upo T0T1 T2T0-T1 T0-T2 T1-T2
(baseline)
(mean ± SD)
(6 mon hs)
(mean ± SD)
(12 mon hs)
(mean ± SD)
P in ag oup P in ag oup P in ag oup
RECdep h (mm) Tes
(CMX)
n = 20
3.69 ± 1.03 1.48 ± 0.73 1.55 ± 0.77 < 0.001 < 0.001 0.448
Con ol (CTG)
n = 20
3.68 ± 0.66 1.18 ± 0.88 1.11 ± 0.78 0.905
P (in e g oup) 0.968 0.314 0.149 - - -
RECwid h (mm) Tes
(CMX)
n = 20
4.15 ± 0.74 2.83 ± 1.02 2.9 ± 0.94 < 0.001 < 0.001 0.866
Con ol (CTG)
n = 20
3.91 ± 0.69 2.38 ± 1.56 2.48 ± 1.58 0.767
P (in e g oup) 0.289 0.478 0.583 - - -
KTW
(mm)
Tes
(CMX)
n = 20
1.79 ± 1.25 2.36 ± 2.47 1.96 ± 1.09 0.307 0.443 0.623
Con ol (CTG)
n = 20
1.78 ± 1.11 2.47 ± 1.3 2.43 ± 1.17 0.004 0.01 0.752
P (in e g oup) 0.968 0.301 0.242 - -
CAL
(mm)
Tes
(CMX)
n = 20
4.88 ± 1.12 2.53 ± 0.78 2.64 ± 0.79 < 0.001 < 0.001 0.14
Con ol (CTG)
n = 20
4.95 ± 0.76 2.35 ± 0.96 2.28 ± 0.87 0.284
P (in e g oup) 0.565 0.738 0.265 - - -
REC dep h (Recession dep h); REC wid h (Recession wid h); KTW (ke a inized issue wid h); CAL (Clinical a achmen le el); SD (s anda d
de ia ion); mm (millime e s); CMX (xenogeneic collagen ma ix); CTG (connec i e issue g a )
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Clinical O al In es iga ions (2024) 28:215
o all pa ame e s (excep KTW and GT) in he con ol
g oup be ween he uppe and lowe jaws, wi h a o able
esul s o he maxilla; in he es g oup, he di e ences
be ween he maxilla and mandible we e only signi ican o
he inc ease in GT.
Resul s o he su gical p ocedu e and PROMs
No pos ope a i e complica ions we e obse ed a e any
su ge y. The esul s a e epo ed in Table 5. The mean su -
gical ime was 45 min (SD:9.01), i.e., 41 min (SD:7.6) (CI
95% 37.41–44.59) in he es g oup and 49.15 min (SD:8.5)
(CI 95% 45.15–53.15) in he con ol g oup; he di e ences
be ween g oups we e signi ican (p = 0.004).
Rega ding he assessmen o pain, less pain was epo ed
by pa ien s who ecei ed CMX, wi h a VAS = 3.65 (SD:2.08)
(95% CI 2.67–4.63) s. VAS = 5.2 (SD:2.31) (95% CI
4.12–6.28) (p = 0.015). Pa ien s in he es g oup we e mo e
and an inc eased in he con ol g oup om 68.70 o
69.72%, espec i ely. The CRC was achie ed in 7
pa ien s (35%) in he es g oup and 8 pa ien s (40%)
in he con ol g oup Th ee pa ien s p esen ed wi h
CRC o all ea ed ecessions in he con ol g oup. A
he ecession le el, he pe cen age o CRC dec eased
in he es g oup ( om 15.5 o 12.1%), and in he con-
ol g oup, i inc eased om 18.9 o 22.6% om 6 o
12 mon hs.
Bo h ea men g oups showed signi ican pos -su gi-
cal imp o emen in all clinical a iables, excep o
he KTW in he es g oup. The GT inc eased a e he
su gical p ocedu es: 0.46 mm (SD:0.54) in he es
g oup and 0.78 mm (SD:0.47) in he con ol g oup
(p = 0.038).
An analysis was pe o med by he ea men g oup ( es
g oup o con ol g oup) and he esul s a e summa ized in
Table 4. S a is ically signi ican di e ences we e obse ed
Table 3 Resul s o clinical changes a six (T1) and wel e (T2) mon hs
Clinical pa ame e G oup T1 T2 P in ag oup
(6 mon hs) (12 mon hs)
MRC (%) Tes
(CMX) n = 20
59.60 ± 16.23 56.48 ± 19.68 0.167
Con ol
(CTG) n = 20
68.70 ± 23.53 69.72 ± 21.21 0.378
P in e g oup 0.163 0.048
CRC (%) Tes
(CMX) n = 20
45 35 0.084
Con ol
(CTG) n = 20
40 40 0.086
P in e g oup 0.64 0.14
REC ed (mm) Tes
(CMX) n = 20
2.21 ± 0.90 2.14 ± 1.07 0.448
Con ol
(CTG) n = 20
2.50 ± 0.84 2.56 ± 0.86 0.905
P in e g oup 0.277 0.181
CAL gain (mm) Tes
(CMX) n = 20
2.36 ± 0.97 2.64 ± 0.79 0.14
Con ol
(CTG) n = 20
2.60 ± 1.10 2.28 ± 0.87 0.284
P in e g oup 0.512 0.221
KTW gain (mm) Tes
(CMX) n = 20
0.57 ± 2.08 0.18 ± 0.84 0.623
Con ol
(CTG) n = 20
0.69 ± 0.85 0.65 ± 0.92 0.752
P in e g oup 0.174 0.114
GT (mm) Tes
(CMX) n = 20
-0.46 ± 0.54 -
Con ol
(CTG) n = 20
-0.78 ±0.47 -
P in e g oup -0.038
MRC (mean oo co e age), CRC (comple e oo co e age), REC ed ( educ ion in ecession); KTW (ke a inized issue wid h); CAL (Clinical
a achmen le el); GT (Gingi al hickness); SD (s anda d de ia ion); % (pe cen age); mm (millime e s); CMX (xenogeneic collagen ma ix);
CTG (connec i e issue g a )
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Clinical O al In es iga ions (2024) 28:215
sco e in he es g oup (6.7 (SD:1.97)) and in he con-
ol g oup (7.28 (SD:2.24)).
Clinical and adiog aphic cha ac e is ics and su gical
p ocedu es o one pa ien om es g oup and con ol
g oup a baseline and 12 mon hs a e shown in Figs. 2
and 3.
Discussion
To ou knowledge, he e is no double-blind andomized
clinical ial in he li e a u e ha compa es he use o a
so issue subs i u e such as he CMX s. he CTG o he
ea men o RT2 ecessions in combina ion wi h CAF, hus
making i di icul o compa e ou esul s wi h ecen e i-
dence [6, 27, 30].
The esul s o his s udy indica ed ha he pe cen age o
MRC was lowe in he es g oup han in he con ol g oup
(CMX: 56.48% s. CTG: 69.72%) (p = 0.048) and ha he
pe cen age o CRC was lowe in he es g oup han in he
con ol g oup (35% s. 40%) a e 12 mon hs; he e o e,
hypo hesis (H0) is ejec ed.
Ou esul s pa ially coincide wi h a ecen me a-analysis
o Mille classes I and II ecessions [18, 38], in which lowe
MRC we e obse ed wi h CMX compa ed wi h CTG, wi h
simila CRC in bo h s udy g oups.
sa is ied wi h he p ocedu e in gene al, bu he di e ences
be ween g oups we e no signi ican .
The aes he ic e alua ion sco e a 12 mon hs was 6.85
(SD:1.5) in he es g oup and 7.15 (SD:1.3) in he
con ol g oup These alues we e simila o he RES
Table 4 Clinical esul s in maxilla and mandible a 12 mon hs o ollow-up
Pa ame e T2Loca ion CMX CTG p in e g oup
MRC (%) Maxilla (n = 9) 65.01 ± 16.83 83.34 ± 15.68 0.015
Mandible (n = 11) 49.49 ± 19.74 58.58 ± 18.83 0.141
p in ag oup 0.152 0.007
CRC
n (%)
Maxilla (n = 9) 55.56 77.78 0.034
Mandible (n = 11) 27.28 9.09 0.72
p in ag oup 0.412 0.012
REC dep h (mm)
(mean ± SD)
Maxilla (n = 9) 2.61 ± 0.97 3.15 ± 0.73 0.297
Mandible (n = 11) 1.76 ± 1.06 2.08 ± 0.67 0.217
p in ag oup 0.08 0.003
REC wid h (mm)
(mean ± SD)
Maxilla (n = 9) 1.6 ± 0.99 2.5 ± 1.48 0.19
Mandible (n = 11) 0.97 ± 0.89 0.57 ± 0.78 0.332
p in ag oup 0.147 0.001
KTW gain (mm)
(mean ± SD)
Maxilla (n = 9) 0.16 ± 1.09 0.87 ± 1.07 0.185
Mandible (n = 11) 0.19 ± 0.63 0.46 ± 0.77 0.401
p in ag oup 0.943 0.33
CAL gain (mm)
(mean ± SD)
Maxilla (n = 9) 2.67 ± 0.97 3.47 ± 0.88 0.222
Mandible (n = 11) 1.89 ± 1.07 2.01 ± 1.03 0.562
p in ag oup 0.08 0.004
GT gain (mm)
(mean ± SD)
Maxilla (n = 9) 0.81 ± 0.55 0.97 ± 0.48 0.481
Mandible (n = 11) 0.17 ± 0.31 0.64 ± 0.44 0.034
p in ag oup 0.004 0.135
MRC (mean oo co e age), CRC (comple e oo co e age), REC ed ( educ ion in ecession); KTW (ke a inized issue wid h); CAL (Clinical
a achmen le el); GT (Gingi a hickness); SD (s anda d de ia ion); % (pe cen age); mm (millime e s); CMX (xenogeneic collagen ma ix);
CTG (connec i e issue g a )
Table 5 Pa ien based su gical pa ame e s and pa ien pe cep ion du -
ing he su ge y
Tes (CMX) Con ol
(CTG)
in e -
g oup
p
N = 20
(mean ± SD)
N = 20
(mean ± SD)
Su gical ime (minu es) 41 ± 7.6 49.15 ± 8.5 0.003
RES 6.74 ± 1.97 7.29 ± 2.24 0.309
PROMs
VAS pos ope a i e pain 3.65 ± 2.08 5.2 ± 2.31 0.015
VAS clinical expe ience 6.4 ± 2.21 5.35 ± 2.08 0.134
VAS aes he ic 6.85 ± 1.5 7.15 ± 1.3 0.64
Su gical ime: du a ion o he su gical p ocedu e (in minu es); RES
( oo co e age es he ic sco e), PROMs: clinical expe ience using a
isual analog scale (VAS) (0 being he wo s p ocedu e and 10 he
bes ); pos ope a i e pain using a isual analog scale (VAS) (0 being
he leas pain and 10 being he maximum pain). Aes he ic esul as
assessed by he pa ien using a isual analog scale (VAS) (0 = wo s
possible aes he ic esul and 10 = excellen aes he ic esul ) SD
(s anda d de ia ion); mm (millime e s); CMX (xenogeneic collagen
ma ix); CTG (connec i e issue g a )
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Clinical O al In es iga ions (2024) 28:215
in ou s udy (35%), hey a e no compa able due o he ype
o ecessions ea ed, whe e he REC ed as well as KTW
gain should be conside ed a ea men success in he ea -
men o gingi al ecessions associa ed wi h loss o in e -
p oximal a achmen [44, 45].
In Chamb one’s 2010 me a-analysis [46], o he ea -
men o RT1 ecessions, in s udies wi h mo e han 10
pa ien s, a 6 mon hs, he CTG yielded e y he e ogeneous
esul s, wi h pe cen ages o MRC (64.5 − 97.3%) and pe -
cen ages o CRC (10 − 96.1%) alues ha coincide wi h a
p e ious e iew [3]. The e o e, ou MRC esul s (CMX:
56.48% s. CTG: 69.72%) o RT2 ecessions a e encou ag-
ing. Howe e , CRC (CMX: 35% s. CTG: 40%) is a om
he esul s o ecessions wi hou inse ion loss, which was
expec ed based on e idence in he li e a u e [6].
A ecen CRC me a-analysis o 37 publica ions abou
hese ypes o ecessions [27] ound wide CRC anges (32.87
− 63.82%). Achie ing CRC o hese ypes o ecessions is
conside ed a challenge because o in e p oximal a ach-
men loss [47], which implies an inc ease in he a ascula
su ace [26, 48]. Ou esul s a e consis en wi h hose p e-
iously epo ed [49] o Mille class III ecessions ea ed
wi h modi ied unnel echnique (TTM) in combina ion wi h
Howe e , he pe cen age o MRC (CMX:56.48% s.
CTG: 69.72%) (p = 0.048) and he pe cen age o CRC
(CMX:35% s. CTG: 40%) esul s o bo h ea men
g oups we e wi hin he anges epo ed in p e ious s udies
o RT2 ecessions wi h CAF + CTG a 12 mon hs (54.8-
77.57%) [39–41]. Only, Fe nández-Jiménez e al. [40],
2023, e alua ed he CRC a 12 mon hs in mul iple eces-
sions wi h esul s (50%) ha we e sligh ly supe io o hose
he ein (40%) whe e he KTW a baseline was highe .
The e idence ega ding CMX is limi ed o RT1 eces-
sions whe e di e en ea men s ha e been compa ed:
(a) CAF + CTG s. CAF + CM [8, 15, 26] (b) CAF s.
CAF + CM [23–25, 42, 43]; (c) Modi ied Co onally
Ad anced Tunnel (MCAT) + CTG s. MCAT + CM [22,
23]. The pe cen age o MRC wi h CMX a 12 mon hs
anged om 76.2% [23] o 94.32% [24]. Ou esul s we e
lowe (56.48%) han he cu en e idence, p obably due o
he ype o ecessions ea ed in his clinical s udy (RT2)
whe e a achmen loss was p esen . Also, only h ee s udies
un il now ha e ea ed mul iple ecessions [8, 24, 25] wi h
CAF + CMX, and CRC was e alua ed in i e s udies p e i-
ously [8, 24–26, 42] and i anged om 36% [42] o 72%
[24]. Al hough hese esul s we e supe io o hose ob ained
Fig. 3 Su gical in e en ion
in a pa ien alloca ed o he
CAF + CTG g oup: (g)(h) clini-
cal and adiog aphic ea u es a
baseline, (i) In a-ope a i e iew:
CTG (j) Immedia e pos ope a i e
iew: co onally lap ad ancemen
and closu e (k)(l) Ou come a
12-mon hs ollow-up
Fig. 2 Su gical in e en ion
in a pa ien alloca ed o he
CAF + CMX g oup. (a)(b) clini-
cal and adiog aphic ea u es a
baseline, (c) In a-ope a i e iew:
CMX, (d) Immedia e pos ope a-
i e iew: co onally lap ad ance-
men and closu e, (e)( ) Ou come
a 12-mon hs ollow-up
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Clinical O al In es iga ions (2024) 28:215
s ep o CEJ whose impo ance has been e idenced in he
ecen 2018 classi ica ion. Also, he so issue ou comes
we e assessed a 12 mon hs, so long- e m obse a ions a e
necessa y o con i m hese esul s. Howe e , his is he i s
double-blinded RCT in RT2 ecessions ha compa es a
CMX and au ogenous g a s, including bo h maxillae (man-
dible:58.5%), and mul iple ecessions (96.39%).
Conclusions
Wi hin he limi a ions o his clinical s udy, al hough MRC
was g ea e wi h CTG we conclude ha CMX is a ea men
op ion o hese challenging RT2 ecessions. The su gical
ime and pa ien mo bidi y we e educed in he es g oup.
The e o e, CMX can be conside ed an al e na i e o au olo-
gous g a s.
I is necessa y o pe o m mo e RCTs in pa ien s wi h
pe iodon i is due o he high p e alence o mul iple eces-
sions in hese pa ien s, which equi e la ge g a s ha en ail
g ea e pos ope a i e mo bidi y.
Acknowledgemen s The au ho s would like o hank o he s a om
Clínica D . Agui e (Bilbao, Bizkaia, Spain) and Clínica Den al La
Casilla, SL (Bilbao, Bizkaia, Spain) o hei collabo a ion. Also, he
au ho s would like o hank o he UPV/EHU o p o iding he Open
Access unding and o Geis lich Pha ma, AG (Wolhusen/ Swi ze land)
o p o iding s udy ma e ials.
Au ho con ibu ions Concep ualiza ion: ERdG-P and LAAZ; me h-
odology: ERdG-P, MVF, AMGF, and LAAZ; da a collec ion: MVF;
o mal analysis and in es iga ion: ERdG-P, MVF, AMGF, and XMM.;
w i ing—o iginal d a p epa a ion:ERdG-P and AMGF; w i ing— e-
iew and edi ing: ERdG-P and AMGF; supe ision: LAAZ; all he au-
ho s e iewed and app o ed he manusc ip .
Funding Open Access unding p o ided hanks o he CRUE-CSIC
ag eemen wi h Sp inge Na u e. S udy ma e ials we e kindly p o ided
by Geis lich Pha ma, AG (Wolhusen/ Swi ze land). Open Access und-
ing p o ided by he Uni e si y o Basque Coun y (UPV/EHU), Leioa,
Biscay, Spain.
Open Access unding p o ided hanks o he CRUE-CSIC ag eemen
wi h Sp inge Na u e.
Da a a ailabili y No da ase s we e gene a ed o analysed du ing he
cu en s udy.
Decla a ions
E hics app o al All p ocedu es pe o med in s udies in ol ing hu-
man pa icipan s we e in acco dance wi h he e hical s anda ds o he
ins i u ional and/o na ional esea ch commi ee and wi h he 1975
Helsinki Decla a ion ( e ised in 2013) and i s la e amendmen s o
compa able e hical s anda ds.
Consen o pa icipa e In o med consen was ob ained om all indi-
idual pa icipan s included in he s udy.
CTG, whe e di e ences be ween he MRC (83%) and he
CRC (40%) we e epo ed. The di e ences wi h ou esul s
in MRC could be due o he su gical echnique [39] and/o
he cha ac e is ics o he sample (ou ecessions we e wide
and had a lowe KTW).
Ad an ages o using al e na i e ma e ials include he
educ ion in in aope a i e ime and pa ien mo bidi y [8],
indings ha we e con i med in his RCT. A educ ion in su -
gical ime o 8 min was obse ed in ou s udy, less han ha
ob ained in a ecen s udy [50], whe e RT1 ecessions we e
ea ed (15 min).
Pa ien sa is ac ion was gene ally highe in he es g oup,
which also p esen ed lowe mo bidi y (p = 0.015); hese
indings con i m p e ious esul s [8], in which he eco e y
ime o pa ien s was sho e (1.8 days) in he CMX g oup,
hus a o ing a be e assessmen o he ea men ecei ed.
Ano he objec i e o hese p ocedu es is o inc ease ke a-
inized issue [18], which is key in ecessions wi h ine phe-
no ypes and in main aining he GM in he long e m [51, 52].
I has been epo ed ha KTW gains a e highe wi h CTG
han wi h CMX, bu wi hou being signi ican [18], which
coincides wi h ou esul s a 6 mon hs, bu no a 12 mon hs,
whe e a g ea e dec ease in KTW was obse ed in he CMX
g oup. The e idence o inc eased GT wi h CMX s. CTG
is limi ed [25]; in his s udy, a 12 mon hs, he e was a end
o inc eased GT wi h he CTG (0.32 mm, p = 0.056), coin-
ciding wi h a di e ence o 0.23 mm in a o o CTG in he
s udy by Ca da opoli e al. [26]. In he CMX g oup, he
hickness gain was g ea e in he uppe maxilla (p = 0.004),
unlike in he con ol g oup, whe e he di e ences be ween
he maxilla and mandible we e no signi ican .
The main indica ion o he ea men o ecessions is
aes he ic demand [53]. The e is no consensus on which
app oach yields mo e aes he ic esul s conce ning CRC
o he simila i y o ea men issue wi h adjacen is-
sue [4, 45]. In ou s udy, he aes he ic assessmen by he
pa ien s was high and simila in bo h g oups (CMX: 6.85
(SD:1.5) s. CTG: 7.15 (SD:1.3)), a inding ha coincides
wi h p e iously epo ed esul s [24], whe e no di e ences
we e obse ed be ween g oups. In con as , a ecen s udy
ob ained a mo e na u al ex u e and con ou wi h CMX
han wi h a CTG [54]. When he p o essional assessmen
was pe o med he RES was simila be ween g oups (CMX:
6.70 (SD:1.97) s. CTG: 7.28 (SD:2.24)) and compa able
o esul s epo ed in he li e a u e [23], i.e., RES o 7.85
(SD:2.42) o CMX and 7.34 (SD:2.90) o CTG. The e o e,
bo h ea men modali ies achie ed sa is ac o y aes he ic
esul s o bo h p o essionals and pa ien s.
Al hough his RCT shows new and ele an in o ma ion
on he ea men o RT2 ecessions, i is no exemp om
limi a ions. Fi s , he e was he lack o assessmen o he lap
hickness ma gin in su ge y o he p esence o de ec able
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