Regeneration of periodontal intrabony defects using platelet-rich fibrin (PRF): a systematic review and network meta-analysis

Vol.:(0123456789)
Odon ology
h ps://doi.o g/10.1007/s10266-024-00949-7
REVIEW ARTICLE
Regene a ion o pe iodon al in abony de ec s using pla ele ‑ ich
ib in (PRF): asys ema ic e iew andne wo k me a‑analysis
FábioF ançaViei aeSil a1 · LuisChauca‑Bajaña2 · Vi oCa loAlbe oCaponio3 ·
Ka eelendAnd einaSegu aCue a4 · By onVelasquez‑Ron5 · Ma iaElenaPadín‑I uegas6 ·
LaysLamolhaAlmeida7· Alejand oIsmaelLo enzo‑Pouso8 · JoséManuelSuá ez‑Peña anda1 ·
Ma ioPé ez‑Sayáns9
Recei ed: 21 Feb ua y 2024 / Accep ed: 4 May 2024
© The Au ho (s) 2024
Abs ac
One o he mos p omising app oaches o co ec pe iodon al bone de ec s and achie e pe iodon al egene a ion is pla ele -
ich ib in (PRF).This sys ema ic e iew and me a-analysis aimed o e alua e he egene a ion o pe iodon al bone de ec s
using PRF compa ed o o he egene a i e ea men s.The da a sea ch and e ie al p ocess ollowed he PRISMA guidelines.
An elec onic sea ch o MEDLINE, Coch ane, and PubMed da abases was pe o med, selec ing exclusi ely andomized
clinical ials whe e he ollowing we e measu ed: p obing dep h educ ion (PD), clinical a achmen le el gain (CAL), and
adiog aphic bone ill (RBF).Ou o 284 selec ed a icles, 32 we e chosen based on inclusion c i e ia. The use o pla ele -
ich ib in (PRF) + open lap deb idemen (OFD), PRF + me o min, PRF + pla ele - ich plasma (PRP), and PRF + OFD/bone
g a (BG) signi ican ly educed PD and imp o ed CAL and RBF. Howe e , he combina ion o PRF + BG, PRF + me o min,
and PRF + STATINS educed CAL. The in e en ion o PRF combined wi h di e en ea men s such as me o min, OFD,
PRP, BG, and STATINS has a signi ican impac on imp o ing PD and CAL. The use o PRF signi ican ly imp o ed he
egene a ion o pe iodon al bone de ec s compa ed o o he ea men s.
Keywo ds Fu ca ion de ec s· Guided pe iodon al issue egene a ion· Pla ele - ich ib in· Pe iodon al disease·
Randomized clinical ial
In oduc ion
Pe iodon al disease is a mul i ac o ial ch onic disease ha
des oys he suppo ing issues o he oo h (bone, cemen ,
and pe iodon al ligamen ) [1, 2]. S udies indica e ha 47%
o 50% o he adul popula ion has pe iodon al disease, and
38.5% a e in mode a e o se e e s ages o he disease (s age
III o s age IV) [3–5]. The main objec i e o pe iodon al
disease ea men is o supp ess in lamma ion by con ol-
ling in ec ion, al hough i is also possible o achie e pa ial
pe iodon al egene a ion in ce ain cases [6]. Pe iodon al
egene a ion is he econs uc ion o he pa o he issues
ha su e ed damage and may be accompanied by he loss
o suppo ing issues [7]. The pa hological p og ession o
pe iodon al disease will gene a e bone eso p ion causing
e ical and/o ho izon al bone de ec s [8]. Pe iodon al
egene a ion seeks o p omo e he g ow h o new issues and
he p ope o ma ion o pe iodon al s uc u es o es o e he
heal h and unc ion o ee h a ec ed by pe iodon al diseases
[9]. Cu en ly, he e a e su gical echniques and egene a i e
ma e ials such as guided issue egene a ion, g ow h ac o s,
enamel ma ix de i a es, bone g a s, ba ie memb anes,
and mesenchymal s em cells ha a e used o epai and
egene a e pe iodon al issue, bone de ec s, a ophic al eola
idge, and u ca ion de ec s [10]. In egene a i e medicine,
he co ec ion o pe iodon al in abony de ec s using pla ele
concen a es (PC) has been s udied [11]. Pla ele - ich plasma
(PRP) eleases g ow h ac o s o issue healing and egen-
e a ion [12, 13], demons a ing ha an icoagulan s in e e e
wi h he angiogenic and egene a i e esponses measu ed
by he pla es [14]. In egene a i e medicine and den is y,
a second-gene a ion pla ele concen a e called pla ele - ich
ib in (PRF) has been in oduced, which does no equi e
Fábio F ança Viei a e Sil a, Luis Chauca-Bajaña and Vi o Ca lo
Albe o Caponio au ho s con ibu ed equally.
Ex ended au ho in o ma ion a ailable on he las page o he a icle
Odon ology
an icoagulan s [15, 16]. Pe iodon al in aosseous de ec s a e
conside ed o ha e good egene a ion po en ial [17]. Se e al
andomized clinical ials (RCTs) ha e been epo ed using
PRF since one o he ad an ages is he o ma ion o dense
ib in clo s wi h pla ele s and leukocy es, which a o s a
mo e p olonged elease o e ime [18, 19]. In addi ion, he
use o PRF in pe iodon al bone de ec s has been s udied in
se e al sys ema ic e iews, which conclude ha i a o s he
healing o pe iodon al issues [20]. The p esen sys ema ic
e iew and me a-analysis aim o e alua e he egene a ion
o pe iodon al bone de ec s using PRF in compa ison wi h
o he egene a i e ea men s.
Ma e ial andme hods
P ospe o da abase was o iginally accessed in May o
2023 and he p o ocol o his sys ema ic e iew and
me a-analysis was submi ed and success ully egis e ed:
CRD42023431418. P e e ed Repo ing I ems o Sys em-
a ic Re iews and Me a-analyses (PRISMA) guidelines we e
ollowed [21].
PICO ques ion
"Is he egene a ion o pe iodon al in abony de ec s wi h
PRF mo e e ec i e han o he echniques?" (P: A icles
wi h s udies o pe iodon al in abony de ec s in humans
we e e alua ed; I: In e en ion, egene a ion o pe iodon al
in abony de ec s pe o med wi h PRF, alone o in combina-
ion wi h o he bioma e ials; C: Compa ison o he di e en
egene a ion esul s o he suppo ing pe iodon al issue wi h
di e en egene a i e ma e ials; O: Obse a ion, he amoun
o pe iodon al egene a ion was compa ed, measu ed by
p obing dep h, clinical a achmen le el, and al eola bone
in he pe iodon al de ec ).
Sea ch s a egy andda abase sc eening
The Rayyan QCRI p og am (Qa a Compu ing Resea ch
Ins i u e, Doha, Qa a ) was used o iden i y eligible a i-
cles. The sea ch s a egy included he sc eening o di e en
da abases, such as MEDLINE h ough PubMed, EMBASE
h ough OVID, Web o Science, Scopus, Coch ane Lib a y,
Clinical T ials, he i e WHO egional bibliog aphic da a-
bases (AIM, LILACS, IMEMR, IMSEAR, WPRIM), and
Con e ence P oceedings Ci a ion Index. A combina ion o
keywo ds and e ms was se and adjus ed o each da abase.
The simple model o keywo ds used we e: "Pla ele - ich
ib in", "Pla ele - ich plasma", "Pe iodon al a achmen
loss", "Al eola bone loss", "Guided issue egene a ion",
"PRF", "Pe iodon al bone de ec s", "Fu ca ion de ec s”;
AND/OR we e also included when sea ching. This p ocess
was complemen ed by a manual sea ch (pee - e iewed jou -
nals wi h ela ed con en ).
Eligibili y c i e ia
Inclusion c i e ia
1. S udies on he egene a ion o bone de ec s wi h PRF in
humans; 2. S udies o andomized clinical ials wi h PRF
alone o wi h o he egene a i e bioma e ials used locally
o co ec pe iodon al de ec s; 3. Regene a ion da a p obing
dep h, clinical a achmen le el, and al eola bone; 4. S ud-
ies published in English.
Exclusion c i e ia
1. S udies including pa ien s wi h diabe es; 2. S udies includ-
ing pa ien s wi h os eopo osis; 3. S udies wi h pa ien s wi h
gene ic modi ica ions; 4. P eclinical in i o o animal
s udies; 5. Pe iodon al egene a ion wi hou using PRF; 6.
S udies ha a e no andomized clinical ials; 7. Clinical
cases, coho , and e ospec i e s udies; 8. S udies o which
measu emen s and s anda d de ia ion da a we e missing; 9.
Re iews, sys ema ic e iews, and me a-analysis.
S udies sc eening andda a ex ac ion
An ad-hoc ex ac ion shee was c ea ed and illed indepen-
den ly by h ee in es iga o s (LC, KS, and MPS) using a
cus omized da a shee . Any doub s ha exis ed be ween
he h ee in es iga o s we e esol ed by h ee in es iga-
o s (BVR, CCC, and REV) who we e unawa e o he s udy
hypo hesis. The ollowing da a we e eco ded: Fi s au ho ,
yea , s udy design, ype o s udy, numbe o people, gen-
de , mean age, ypes o de ec s, in e en ion g oups, con ol
g oup, smoke s, conclusions, mean di e ence (MD) in p ob-
ing dep h (PD), clinical a achmen le el (CAL), al eola
bone, spin sys em, he olume o blood d awn, and spin
pa ame e s (Table1; Supplemen a y Table1).
Assessmen o  isk o bias (RoB)
Two au ho s (MS, VM) independen ly assessed he included
epo s, using all checklis i ems o he espec i e scales.
The Coch ane Risk o Bias Tool o Randomized Con olled
T ials was used o assess andomized con olled ials [22].
Odon ology
Table 1 Gene al o e iew o he included s udies
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
OFD s PRF
Sha ma and
P adeep 2011
[15]
RCT pa allel 9mon hs 42 24M 18 F 35.3 3 walls T: 28, OFD + PRF C: 28 OFP No G ea e educ ion
in p obing dep h,
CAL gain, and
bone ill a PRF-
ea ed si es wi h
con en ional open-
lap deb idemen
Tho a e al. 2011
[16]
RCT pa allel 9mon hs 32 20M 12 F 30.7 2 and 3 walls T: 16, OFD + PRF C: 16, OFD No G ea e educ ion
in PD, mo e CAL
gain, and g ea e
illing o in abony
de ec s in he PRF-
ea ed si es
Rosamma e al.
2014 [17]
TC spli mou h 12mon hs 15 6M 9 F 29.5 2 and 3 walls T: 15, OFD + PRF C: 15, OFD No Clinically, he use
o PRF in bo h
gel and memb ane
o ms is mo e
e ec i e han open
lap deb ide-
men alone in he
managemen o
ho izon al pe i-
odon al de ec s
Ajwani e al. 2015
[18]
RCT 9mon hs 20 10M 20 F 30.5 2 and 3 walls T: 20, OFD + PRF C: 20, OFD No The complemen a y
use o PRF wi h
OFD signi ican ly
imp o es de ec
illing compa ed o
OFD alone
Bajaj e al. 2017
[19]
RCT 9mon hs 17 9M 8 F 29.7 2 and 3 walls T: 27, OFD + PRF C: 27, OFD No The e is g ea e
bone ill in he
PRF- ea ed a eas
wi h con en ional
OFD han wi h
con en ional OFD
alone
Pa el e al. 2017
[20]
RCT 12mon hs 13 4M 9 F 44 2 and 3 walls T: 13, OFD + PRF C: 13, OFD No The use o PRF wi h
con en ional OFD
can po en ially be
used in he ea -
men o pe iodon-
al bone de ec s
Odon ology
Table 1 (con inued)
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
P adeep e al. 2017
[21]
RCT 9mon hs 62 34M 28 F 39.7 3 walls T1: 19, OFD + PRF, T2:
20, OFD + PRF + HA
C: 18, OFD No PRF esul s in sig-
ni ican imp o e-
men s o clinical
pa ame e s. When
added o PRF,
HA augmen s
he egene a i e
e ec s seen wi h
PRF in 3-wall IBD
ea men
Tho a e al. 2017
[22]
RCT 12mon hs 15 7M 8 F 25 3 walls T: 15, OFD + PRF C: 15, OFD - The use o PRF sig-
ni ican ly imp o es
he clinical and
adiog aphic
esul s o open lap
deb idemen in he
ea men o pe i-
odon al in abony
de ec s in pa ien s
a ec ed by local-
ized agg essi e
pe iodon i is
BG s PRF
Ma hu e al. 2015
[23]
RCT 6mon hs 25 14M 11 F 39.7 2 and 3 walls T: 19, OFD + PRF C: 19,
OFD + ABG
No The use o PRF o
ABG was e ec i e
in he ea men
o h ee-wall pe i-
odon al in abony
de ec s wi h
une en ul healing
o he si es
Shah e al. 2015
[24]
RCT 6mon hs 20 - - 2 and 3 walls T: 20, OFD + PRF C: 20,
OFD + DFDBA
No PRF has shown
signi ican esul s
a e 6mon hs,
which is compa-
able o DFDBA
o pe iodon al
egene a ion
Odon ology
Table 1 (con inued)
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
Chadwick
e al. 2016 [25]
RCT 6mon hs 36 20M 16 F 54.9 2 and 3 walls T: 17, OFD + PRF C: 19,
OFD + DFDBA
Yes T ea men o pe i-
odon al in abony
de ec s wi h
DFDBA o PRF
esul ed in a
signi ican gain
in CAL and bone
ill a e 6mon hs
o healing, wi h
no signi ican di -
e ences be ween
ma e ials
Gala e al. 2016
[26]
RCT 9mon hs 20 - 45 2 and 3 walls T: 20, OFD + PRF C: 20,
OFD + ABG
No Bo h ABG and PRF
can be used in
p edic able ways
o ebuild los pe i-
odon al s uc u es
as indica ed by
PPD educ ion
and RAL gain.
Howe e , in e ms
o illing bone
de ec s, ABG
p oduces a mo e
de ini i e esul
han PRF
Yajamanya
e al. 2017 [7]
RCT 9mon hs 32 - - 2 and 3 walls T1: 28, OFD + BioG
T2: 28, OFD + PRF
C: 28, OFD No Signi ican imp o e-
men s in clinical
pa ame e s and
adiog aphic
esul s wi h
Pe ioGlas ® and
au ologous PRF o
ea pe iodon al
in abony de ec s
compa ed o OFD
alone
BG s BG + PRF

Odon ology
Table 1 (con inued)
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
Bansal and Bha i
2013 [27]
RCT 6mon hs 10 - - - T: 10,
OFD + DFDBA + PRF
C: 10,
OFD + DFDBA
- Combining PRF
wi h DFDBA dem-
ons a ed be e
esul s in p obing
dep h educ-
ion and clinical
a achmen le el
gain compa ed o
DFDBA alone in
he ea men o
pe iodon al in a-
bony de ec s
Elgendy and Abo
Shady 2015 [28]
RCT 6mon hs 20 - 44 - T: 20, OFD + HA + PRF C: 20,
OFD + NcHA
Yes NcHA bone g a ing
in combina ion
wi h PRF dem-
ons a ed clinical
ad an ages beyond
hose achie ed by
NcHA alone
Aga wal e al. 2016
[29]
RCT 12mon hs 30 15M 15 F 52 2 and 3 walls T: 30, OFD + DFDBA/
PRF
C: 30,
OFD + DFDBA
No Combina ion o
PRF and DFDBA
is mo e e ec i e
han DFDBA wi h
saline o he ea -
men o in abony
pe iodon al de ec s
Naq i e al. 2017
[30]
RCT 9mon hs 10 7M 3 F N/R 2 and 3 walls T: 10, OFD + BioG + PRF C: 10,
OFD + BioG
No The esul s o his
s udy showed ha
BioG pu y alone
om bo h g oups
and he combina-
ion o PRF and
BioG pu y a e
e ec i e in he
ea men o sub-
bony pe iodon al
de ec s
Sezgin e al. 2017
[31]
RCT 6mon hs 15 8M 7 F N/R 2 and 3 walls T: 15,
OFD + ABBM + PRF
C: 15,
OFD + ABBM
No Bo h he apies a e
e ec i e in he
ea men o in a-
bony de ec s
Odon ology
Table 1 (con inued)
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
Liu e al. 2021 [32] RCT 12mon hs 15 4M 11 F 36.0 ± 8.6 -T: 14 BPBM + PRF C: 14 BPBM No The BPBM-PRF
complex is clini-
cally mo e e ec-
i e and p oduces
be e clinical
esul s
Paolan onio e al.
2020 [33]
RCT 12mon hs 44 15M 29 F 53 ± 12 1 and 2 walls T: 22 L-PRF and ABG C: 22 EMD + ABG No The esul s sug-
ges ha he
L-PRF + ABG
combina ion ea -
men o uncon-
ained IBD p o-
duces non-in e io
esul s in e ms
o CAL inc ease,
PPD educ ion,
GR inc ease, and
DBL inc ease
compa ed o he
EMD + ABG
combina ion
Bodha e e al. 2019
[34]
RCT 6mon hs 20 11M 9 F 35.9 2 and 3 walls T: 20, OFD + Bioac i e
Glass + PRF
C: 20, OFD + Bio-
ac i e Glass
No The use o Bioac-
i e Glass, when
used in combina-
ion wi h PRF,
is mo e e ec i e
in gaining CAL,
educing PPD,
and achie ing
g ea e bone ill
compa ed o BG
ea men alone in
pe iodon al and
in abony de ec s.
i is indica i e o
imp o ed pe i-
odon al egene a-
ion
BM s PRF
Odon ology
Table 1 (con inued)
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
Pham 2021 [35] RCT 12mon hs 30 22M 8 F 47.9 2 and 3 walls T: 30 PRF + OFD C: 30 GRUPO 2
BM + GTR Y 30
GRUPO 3 OFD
No Compa ed o GTR,
PRF yielded com-
pa able pe iodon-
al issue healing
and ea men
esul s in e ms o
imp o emen s in
clinical and adio-
g aphic pa am-
e e s. Compa ed
wi h OFD alone,
PRF also signi i-
can ly imp o ed
hese pa ame e s
in he ea men o
in abony de ec s
Us aoğlu e al.
2020 [36]
RCT 9mon hs 45 23M 22 F 40 ± 8.37 In abony de ec s
associa ed wi h
a p ima y pe i-
odon al lesion
wi h second-
a y endodon ic
in ol emen o
ue combined
endodon ic-pe -
iodon al lesions
in single- oo ed
ee h
T: 15 PRF + OFD C: 15 BM + GTR
GRUPO 2 Y 15
OFD GRUPO 3
No PRF can gi e simila
success ul esul s
o GTR in he
ea men o IBD
wi h endo-pe io
lesions
Panda e al. 2016
[37]
RCT 9mon hs 18 10M 8 F 38.1 3 walls T: 18, OFD + BM + PRF C: 18, OFD + BM No The adjunc i e use
o PRF in com-
bina ion wi h he
ba ie memb ane
is mo e e ec i e
in he ea men o
in abony de ec s
in ch onic pe i-
odon i is compa ed
o he ba ie
memb ane alone
PRP s PRF
Odon ology
Table 1 (con inued)
Au ho S udy design Follow-up Sample size Gende A e age age Types o de ec s In e en ion g oup Con ol g oup Smoke s Conclusion
P adeep e al. 2012
[38]
RCT 9mon hs 54 27M 27 F 36.8 3 walls T1: 17, OFD + PRP T2:
16, OFD + PRF
C: 17, OFD No Simila educ ion o
PD, CAL gain and
BF in PRF o PRP
ea ed si es wi h
con en ional OFD
EMD s PRF
Gup a e al. 2014
[39]
RCT 6mon hs 30 15M 15 F - 3 walls T: 22, OFD + PRF C: 22,
OFD + EMD
No Bo h Emdogain and
pla ele - ich ib in
we e e ec i e
in egene a ing
in abony de ec s.
Emdogain was
signi ican ly supe-
io in e ms o
de ec esolu ion
pe cen age
Csi óNagy 2021
[40]
RCT 6mon hs 18 9M 9 F 55,5 ± 14,5 2 and 3 walls T: 15, OFD + PRF C: 15 OFD + EMD No New gene a ion PRF
appea s o be as
clinically e ec i e
as DME du ing
su gical ea -
men o in abony
de ec s
EMD s
EMD + PRF
Aydemi Tu kal
e al. 2016 [41]
RCT 6mon hs 28 14M 14 F 38.5 1, 2 and 3 walls T: 25, OFD + EMD + PRF C: 24,
OFD + EMD
No Bo h he apies
esul ed in sig-
ni ican clinical
imp o emen in
IBD ea men .
The addi ion
o PRF did no
imp o e clinical
and adiog aphic
esul s
PRF s PRF + me -
o min
Odon ology
ep esen a i e ea men g oup, ollowed by blood clo s
and bone illing.
O e all inconsis ency esul ed in p esen a he global
le el (p- alue = 0.006), while a he local le el, only
blood clo s e sus BM and PRF e sus BM yielded local
inconsis ency (p- alues 0.012 and 0.033 espec i ely).
Visualiza ion o he inconsis ency was igu ed in he
ne wo k o es plo , in which e ec sizes by s udy we e
g aphically ep esen ed (Fig.6B).
Fig. 4 Ne wo k geome y plo o PD g oup analysis and Ne wo k
o es plo o PD g oup analysis. A Mos o he compa isons we e
a low isk o bias, howe e , he main one, PRF s. blood clo s p e-
sen ed mode a e bias; B O e all inconsis ency esul ed in absence a
global (p- alue = 0.558) and local le els (p- alue anging be ween
0.139 o 0.997. The le e s co esponds o: A = ROSU1.2% + PRF;
B = BF1% + PRF; C = MF1% + PRF; D = Bone Fill + PRF;
E = 1.2%ATV + PRF; F = EMD + PRF; G = Bone Fill; H = PRF + HA;
I = EMD; J = BM; K = PRF; L = MF1%; O = PRP; P = BF; Q = ATV;
U = Blood Clo . The ac onym co esponds o: PRF: Pla ele -Rich
Fib in; HA: Hyd oxyapa i e; BM: Ba ie Memb ane; EMD: Enamel
Ma ix De i a i e; PRP: Pla ele -Rich Plasma; BF: Bone Fille ; MF:
Me Fo min; ROSU = Rosu as in; ATV = A o as a in [7, 12, 30–59]
Fig. 5 Ne wo k geome y plo o CAL g oup analysis and Ne wo k
o es plo o CAL g oup analysis. A Mos o he compa isons we e
a low isk o bias, howe e , he main one, PRF s. blood clo s p e-
sen ed mode a e bias; B O e all inconsis ency esul ed in absence a
global (p- alue = 0.567) and local le els (p- alue anging be ween
0.102 o 0.996. The le e s co esponds o: A = Bone Fill + PRF;
B = BF1% + PRF; C = MF1% + PRF; D = 1.2%ROSU + PRF;
E = EMD + PRF; F = 1.2%ATV + PRF; G = Bone Fill; H = EMD;
I = PRF + HA; J = PRF; K = PRP; L = BM; O = MF1%; P = ATV;
Q = BF; U = Blood Clo . The ac onym co esponds o: PRF: Pla ele -
Rich Fib in; HA: Hyd oxyapa i e; BM: Ba ie Memb ane; EMD:
Enamel Ma ix De i a i e; PRP: Pla ele -Rich Plasma; BF: Bone
Fille ; MF: Me Fo min; ROSU = Rosu as in; ATV = A o as a in [7,
12, 30–59]

Odon ology
Among he 15 in e en ions, wi h su p ise, 3 led o wo se
RBF (PRP, BF, and ATV). All he o he ea men s we e
cha ac e ized by imp o ed RBF compa ed o blood clo s,
howe e , seeing he la ge p edic i e in e als, hese in e -
en ions could lead o unsuccess ul esul s in u u e ials.
Only PRF and PRF combined wi h HA led o s a is ically
signi ican RBF imp o emen s since hei con idence in e -
al did no c oss he line o null e ec . PRF + HA led o he
highes RBF and was s a is ically signi ican compa ed o
PRP, BF, ATV, and blood clo s. All he o he in e en ions
demons a ed lowe RBF, howe e , compa ed o PRF + HA,
hese di e ences we e no s a is ically signi ican .
Visualizing esul s based on SUCRA sco es, op- anked
ea men esul ed combina ion o PRF and HA, wi h a mean
ank o 3.5 among all he in e en ions and a SUCRA alue
o 83.7. O in e es , MF and PRF + MF esul ed in he bes
second and ou h in e en ions. In his case, a combina ion
o bone wi h PRF led o op- anked esul s, as he hi d-bes
in e en ion. De ailed SUCRA alues and mean ank a e
illus a ed in Supplemen a y Fig.4.
Discussion
PD g oup
STATISTS s. PRF has he la ges sample size bu is no
signi ican be ween he s udy g oups, howe e , we can spe-
ci ically di ec ha he BIPHOSPHONATES s. PRF, OFD
s. PRF, and PRF s. PRF g oups esul ed in s a is ical sig-
ni icance wi h a p- alue < 0.05. These esul s a e e iden
a CI95% in he posi ion o he diamond in he o es plo
(Fig.1) in each g oup o s udies.
The g oup o s udies BG s. BG + PRF is no signi ican ,
bu s udies such as Bansal and Bha i [42], Aga wal e al.
[44], and Kano iya e al. [57] ha e s a is ically signi ican
isk ac o s. Howe e , Us aoglu e al. [51] a e signi ican as
a p o ec i e ac o . Ma ande e al. [58] and P adeep e al.
[59] a e signi ican wi h a isk ac o o he egene a i e
po en ial o PRF only in pe iodon al bone de ec s. Gala
e al. [41] and Yajamanya e al. [12] a e highly signi ican
wi h p o ec i e isk o he use o ABG o PRF as a ebuilde
o pe iodon al s uc u es, and signi ican wi h a isk ac o
o adiog aphic esul s wi h Pe ioGlas and PRF. P adeep
e al. [56] is a signi ican s udy wi h a isk ac o o he PRF
g oup + MF1%. The s udies o Sha ma and P adeep [30],
Tho a e al. [31], Rosamma e al. [32], Bajaj e al. [34],
Pa el e al. [35], P adeep e al. [59], and Tho a e al. [37]
a e highly signi ican s udies wi h con ol isk. The P adeep
e al. [53] s udy is s a is ically signi ican o he con ol isk
in he PD educ ion and gain o CAL and BF (Fig.1).
CAL g oup
The esul s by g oups o s udies indica e ha , acco ding o
Bila e al Signi icance, hose less han 0.05 a e s a is ically
signi ican , o his he g oups a e BIPHOSPHONATES s.
Fig. 6 Ne wo k geome y plo o RBF g oup analysis and Ne wo k
o es plo o RBF g oup analysis. A Mos o he compa isons we e
a low isk o bias, howe e , he main one, PRF s. blood clo s p e-
sen ed mode a e bias; (B) O e all inconsis ency esul ed in he p e-
sen a he global le el (p- alue = 0.006), while a he local le el,
only blood clo s e sus BM and PRF e sus BM yielded local incon-
sis ency (p- alues 0.012 and 0.033 espec i ely). The le e s co e-
sponds o: A = PRF + HA; B = MF1% + PRF; C = Bone Fill + PRF;
D = MF1%; E = BF1%PRF; F = BM; G = 1.2%ATV + PRF; I = EMD;
J = EMD + PRF; K = PRF; L = Bone Fill; O = Blood Clo ; P = BF;
Q = ATV; U = PRP. The ac onym co esponds o: PRF: Pla ele -Rich
Fib in; HA: Hyd oxyapa i e; BM: Ba ie Memb ane; EMD: Enamel
Ma ix De i a i e; PRP: Pla ele -Rich Plasma; BF: Bone Fille ; MF:
Me Fo min; ROSU = Rosu as in; ATV = A o as a in [7, 12, 30–59]
Odon ology
PRF, STATISTAS s. PRF, METFORMIN s. PRF, OFD
s. PRF, as well as all he s udies in a global way u n ou o
be signi ican using CAL.
In he analysis o esul s wi hin he g oups, we also ound
he s udies ha ha e s a is ical signi icance, in he BG s.
BG + PRF g oup he s udy Bansal and Bha i [42], and
Aga wal e al. [44] whe e PRF and ADFDB a e mo e e ec-
i e han ADFDB wi h saline solu ion. Liu e al. whe e he
BPBM-PRF complex is clinically mo e e ec i e wi h e ec-
i e esul s. BIPHOSPHANES s. PRF Kano iya e al. [57]
was he ocused he apy combining PRF + ALN 1% o he
ea men o IBD in pa ien s. In he BM s. PRF g oup, he
s udies by Panda e al. [52] a e signi ican wi h 72% sensi-
i i y whe e PRF in combina ion wi h ba ie memb ane is
mo e e ec i e. Pham e al. [50] a e signi ican wi h a p- alue
o 0.00 whe e PRF ga e posi i e esul s o pe iodon al is-
sue. Us aoglu e al. [51] a e signi ican wi h a p- alue o
0.00 whe e he PRF can gi e posi i e esul s as GTR in he
ea men o IBD. In he g oup o STATISTS s. PRF, we
ound ha he s udy by Ma ande e al. [58] is signi ican
wi h 73% o sensi i i y o con ol isk (Fig.2).
P adeep e al. [59] a e signi ican whe e OFD wi h ROSU
1.2% and PRF p oduce pe iodon al bene i s. In he BONE
s. PRF g oup, he Gala e al. [41] s udy is s a is ically
signi ican whe e ABG as PRF can be used p edic ably o
he econs uc ion o pe iodon al s uc u es. In he MET-
FORMIN s. PRF g oup, P adeep e al. [56] a e signi ican
wi h con ol isk whe e he PRF + MF 1% g oup was mo e
e ec i e han MF, PRF, o OFD. Fo he g oup o OFD
s. PRF s udies, he s udies o Tho a e al. [31], Rosamma
e al. [32], Ajwani e al. [33], Bajaj e al. [34], Pa el e al.
[36], P adeep e al. [59], Tho a e al. [37] a e signi ican o
con ol isk (Fig.2).
Bone g oup
The s udy g oups we e s a is ically signi ican due o
he p- alue o less han 0.05, in such a way ha BG s.
BG + PRF, BIPHOSPHONATES s. PRF, OFD s. PRF,
and PRP s. PRF. A he global le el o all he esul s o he
s udy g oups, signi icance is e idenced wi h a Z alue o
3.605 and an e ec size o 1.537.
When analyzing he Fo es Plo g aph (Fig.3), i is e i-
den ha he o e all esul is ela i ely he e ogeneous wi h
an e ec size o 1.537, wi h o al isk. Howe e when ana-
lyzing he g oups o s udies, al hough he e a e no signi i-
can esul s, he speci ic s udies deno e signi icance due o
he esul s’ cha ac e is ics. In he BG s. BG + PRF g oup,
signi icance is e idenced in he s udy by Aga wal e al. [44],
Naq i e al. [45], Sezgin e al. [46], and Bodha e e al. [49].
Fo he BM s. PRF g oup, he Panda e al. [52] and
Pham [50] s udies we e signi ican wi h con ol isk, while
he Us aoglu e al. [51] s udy is signi ican wi h p o ec-
i e isk. In he STATISTA s. PRF g oup, he s udies
o Ma ande e al. [58], and P adeep e al. [59] we e sig-
ni ican o con ol isk. In he BONE s. PRF g oup, he
s udy by Gala e al. [41] gene a ed signi icance wi h a
s anda d e o o 0.33. In he g oup o OFD s. PRF s ud-
ies, he s udies by Sha ma and P adeep [30], Tho a e al.
[31], Rosamma e al. [32], Ajwani e al. [33], Bajaj e al.
[34], P adeep e al. [59], Tho a e al. [37] we e signi ican
as con ol isk. In he PRP s. PRF g oup, he s udy by
P adeep e al. [46] is signi ican wi h con ol isk, wi h a
s anda d e o o 0.24 (Fig.3).
Conclusi e NMA discussion
The p esen sys ema ic e iew and me a-analysis sugges
ha using PRF o egene a e pe iodon al bone de ec s in
humans may be e ec i e compa ed o o he egene a i e
echniques. Howe e , i is impo an o no e ha esul s
may a y depending on se e al ac o s, including he ype
o pe iodon al de ec , he su gical echnique used, and he
quali y o he s udies included.
Despi e i s wide applica ion in clinical p ac ice, he e
is s ill con o e sy ega ding which ype o plasma con-
cen a e can p o ide be e esul s in ela ion o bone o -
ma ion. P e ious s udies demons a e ha PC ha e some
ad an ages, such as he o ma ion o new abecula bone,
apid eso p ion, and healing due o a ious g ow h ac-
o s. A combina ion o a ma e ial wi h low eso p ion,
one ha p ese es he olume o he socke , oge he wi h
ano he ma e ial ha a o s he o ma ion o new bone,
is supposed o be a good choice o p omo e osseoin eg a-
ion and p ima y s abili y. O he s udies ha e also epo ed
ha al eola idge p ese a ion (ARP) combined wi h any
o he ma e ial is supe io o spon aneous healing [60].
The p esen s udy shows us ha PRF use was he mos
ep esen a i e ea men g oup in he ea men o PS, ol-
lowed by blood clo s and bone illing. Howe e , he mix-
u e o PRF wi h bone g a showed be e esul s han he
use o bone ille and PRF alone. Howe e , hese esul s
do no p esen s a is ical signi icance and wide p edic i e
in e als, which could esul in null esul s in u u e clini-
cal ials.
In he NBF g oup, i is possible o obse e ha he mos
e ec i e in e en ion was he combina ion o bone and PRF.
This combina ion p oduced s a is ically signi ican supe io
esul s compa ed o PRF o bone alone. The addi ion o BF
o PRF esul ed in a simila NBF wi h he combina ion o
bone and PRF. Howe e , he highes - a ed ea men was
he combina ion o bone and PRF, wi h an a e age a ing o
h ee ac oss all in e en ions and a SUCRA alue o 86.3.
Odon ology
Limi a ions
One o he p ima y limi a ions o his sys ema ic e iew
and me a-analysis is he he e ogenei y among he included
s udies. Va ia ions in s udy design, pa ien demog aph-
ics, ypes o pe iodon al de ec s, su gical echniques, and
PRF p epa a ion p o ocols may ha e con ibu ed o sig-
ni ican he e ogenei y in he esul s. This he e ogenei y
makes i challenging o d aw de ini i e conclusions and
may limi he gene alizabili y o he indings. Despi e
e o s o include a wide ange o ele an s udies, pub-
lica ion bias emains a po en ial limi a ion. The quali y
o he included s udies is c ucial o he alidi y o he
me a-analysis esul s. While e o s we e made o assess
he isk o bias in indi idual s udies using he Coch ane
Risk o Bias Tool, some s udies may ha e inhe en limi a-
ions ha we e no ully accoun ed o . The indings o
his me a-analysis a e based on a speci ic se o inclusion
and exclusion c i e ia, including he es ic ion o s udies
conduc ed in humans, published in English, and in ol -
ing non-smoking pa ien s. This selec i i y may limi he
gene alizabili y o he esul s o b oade popula ions o
clinical scena ios. The included s udies may ha e used
di e en PRF p epa a ion p o ocols, including a ia-
ions in cen i uga ion speed, du a ion, and he addi ion
o ac i a o s. These di e ences in PRF p epa a ion could
impac he elease o g ow h ac o s and o he he apeu ic
componen s, po en ially in luencing ea men ou comes.
Many o he included s udies may ha e ela i ely sho
ollow-up pe iods, which could limi ou unde s anding
o he long- e m e ec i eness and s abili y o PRF in
pe iodon al egene a ion. Ideally, longe - e m ollow-up
da a would p o ide a mo e comp ehensi e assessmen
o ea men success. The analysis p ima ily ocused on
p obing dep h (PD), clinical a achmen le el (CAL), and
adiog aphic bone ill (RBF) as ou come measu es. While
hese a e essen ial pa ame e s o assessing pe iodon al
egene a ion, o he clinical and pa ien - epo ed ou comes
may p o ide a mo e comp ehensi e e alua ion o ea -
men success. Despi e e o s o g oup s udies based on
simila in e en ions, he e may s ill be clinical he e oge-
nei y wi hin he ea men g oups. Va ia ions in su gical
echniques, ope a o skills, and pa ien compliance could
in oduce addi ional a iabili y in he esul s.
Conclusion
Based on he esul s o his sys ema ic e iew and me a-
analysis, he use o PRF appea s o be a p omising op ion
o he egene a ion o pe iodon al bone de ec s in humans.
Howe e , mo e high-quali y andomized clinical ials a e
needed o con i m hese indings and p o ide mo e p ecise
guidance on he clinical use o PRF in den al p ac ice.
Supplemen a y In o ma ion The online e sion con ains supplemen-
a y ma e ial a ailable a h ps:// doi. o g/ 10. 1007/ s10266- 024- 00949-7.
Au ho con ibu ions FFVS conduc ed s udy design, da a analysis,
in e p e ed esul s, and w o e he epo . LCB, KASC, BVR, and
RAVC we e esponsible o conduc ing he sea ch, sc eening po en-
ially eligible s udies, da a ex ac ion, and c ea ion o ables. VCAC
and AILP con ibu ed o he s a is ics s udy design and conduc ed he
s a is ics analysis. LLA was esponsible o p o iding eedback abou
he pe iodon ology he ms. MEPI, JMSP, and MPS we e esponsible
o designing he e iew p o ocol and p o iding eedback on he epo .
Funding Open Access unding p o ided hanks o he CRUE-CSIC
ag eemen wi h Sp inge Na u e. No unding.
Da a A ailabili y The da a o suppo he indings o his s udy will be
a ailable on eques om he co esponding au ho J.M.S.P.
Decla a ions
Con lic o in e es The au ho s decla e no con lic s o in e es and no
compe ing inancial in e es s.
Open Access This a icle is licensed unde a C ea i e Commons A i-
bu ion 4.0 In e na ional License, which pe mi s use, sha ing, adap a-
ion, dis ibu ion and ep oduc ion in any medium o o ma , as long
as you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce,
p o ide a link o he C ea i e Commons licence, and indica e i changes
we e made. The images o o he hi d pa y ma e ial in his a icle a e
included in he a icle’s C ea i e Commons licence, unless indica ed
o he wise in a c edi line o he ma e ial. I ma e ial is no included in
he a icle’s C ea i e Commons licence and you in ended use is no
pe mi ed by s a u o y egula ion o exceeds he pe mi ed use, you will
need o ob ain pe mission di ec ly om he copy igh holde . To iew a
copy o his licence, isi h p://c ea i ecommons.o g/licenses/by/4.0/.
Re e ences
1. Cu is MA, Diaz PI, Van Dyke TE. The ole o he mic obio a in
pe iodon al disease. Pe iodon ol. 2020;83(1):14–25.
2. Muñoz-Salgado A, Sil a FF, Padín-I uegas ME, Camolesi GC,
Be naola-Pa edes WE, Ve onese HR, e al. Leukocy e and pla ele
ich ib in in he managemen o medica ion- ela ed os eonec osis
o he jaw: a sys ema ic e iew and me a-analysis. Med O al Pa ol
O al Ci Bucal. 2023;28(4):317–29.
3. Chauca-Bajaña L, Velasquez-Ron B, Tomás-Ca mona I, Cama-
cho-Alonso F, Pé ez-Ja dón A, Pé ez-Sayáns M. Regene a ion o
pe iodon al bone de ec s wi h mesenchymal s em cells in ani-
mal models Sys ema ic e iew and me a-analysis. Odon ology.
2023;111(1):105–22.
4. Nazi M, Al-Ansa i A, Al-Khali a K, Alha eky M, Ga a B,
Almas K. Global p e alence o pe iodon al disease and lack o
i s su eillance. Sci Wo ld J. 2020;2020:2146160.
5. Mi on RJ, Mo aschini V, Fujioka-Kobayashi M, Zhang Y, Kawase
T, Cosga ea R, e al. Use o pla ele - ich ib in o he ea men
o pe iodon al in abony de ec s: a sys ema ic e iew and me a-
analysis. Clin O al In es . 2021;25(5):2461–78.
6. Nuñez J, Vignole i F, Ca esse RG, Sanz M. Cellula he apy in
pe iodon al egene a ion. Pe iodon ol. 2019;79(1):107–16.
Odon ology
7. Csi ó-Nagy BK, Sólyom E, Bogná VL, Ne eli s A, Dő i F. E i-
cacy o a new-gene a ion pla ele - ich ib in in he ea men o
pe iodon al in abony de ec s: a andomized clinical ial. BMC
O al Heal h. 2021;21(1):580.
8. Liu Y, Guo L, Li X, Liu S, Du J, Xu J, e al. Challenges and issue
enginee ing s a egies o pe iodon al-guided issue egene a ion.
Tissue Eng Pa C Me hods. 2022;28(8):405–19.
9. Liu J, Ruan J, Wei MD, Ren K, Schneide A, Wang P, e al. Pe i-
odon al bone-ligamen -cemen um egene a ion ia sca olds and
s em cells. Cells. 2019;8(6):537.
10. Jepsen S, Gennai S, Hi sch eld J, Kalemaj Z, Bu i J, G aziani F.
Regene a i e su gical ea men o u ca ion de ec s: a sys ema ic
e iew and bayesian ne wo k me a-analysis o andomized clinical
ials. J Clin Pe iodon ol. 2020;47(Suppl 22):352–74.
11. Najeeb S, Khu shid Z, Agwan MAS, Ansa i SA, Za a MS, Ma in-
linna JP. Regene a i e po en ial o pla ele ich ib in (PRF) o
cu ing in abony pe iodon al de ec s: a sys ema ic e iew o clini-
cal s udies. Tissue Eng Regen Med. 2017;14(6):735–42.
12. Yajamanya SR, Cha e jee A, Hussain A, Cou inho A, Das S,
Subbaiah S. Bioac i e glass e sus au ologous pla ele - ich ib in
o ea ing pe iodon al in abony de ec s: a compa a i e clinical
s udy. J Indian Soc Pe iodon ol. 2017;21(1):32–6.
13. Pi zu a L, Jansen IDC, de V ies TJ, Hoogenkamp MA, Loos
BG. E ec s o L-PRF and A-PRF+ on pe iodon al ib oblas s
in in i o wound healing expe imen s. J Pe iodon al Res.
2020;55(2):287–95.
14. One o P, Zubi y PR, Scha ne M, E ulain J. An icoagulan s in e -
e e wi h he angiogenic and egene a i e esponses media ed by
pla ele s. F on Bioeng Bio echnol. 2020;8:223.
15. Chouk oun J, Diss A, Simonpie i A, Gi a d MO, Schoe le
C, Dohan SL, e al. Pla ele - ich ib in (PRF): a second-gen-
e a ion pla ele concen a e. Pa IV: clinical e ec s on issue
healing. O al Su g O al Med O al Pa hol O al Radiol Endod.
2006;101(3):56–60.
16. Mi on RJ, Fujioka-Kobayashi M, He nandez M, Kandalam U,
Zhang Y, Ghanaa i S, e al. Injec able pla ele ich ib in (i-PRF):
oppo uni ies in egene a i e den is y? Clin O al In es ig.
2017;21(8):2619–27.
17. Sculean A, Nikolidakis D, Nikou G, I ano ic A, Chapple ILC,
S a opoulos A. Bioma e ials o p omo ing pe iodon al egene a-
ion in human in abony de ec s: a sys ema ic e iew. Pe iodon ol.
2015;68(1):182–216.
18. Fujioka-Kobayashi M, Mi on RJ, He nandez M, Kandalam U,
Zhang Y, Chouk oun J. Op imized pla ele - ich ib in wi h he
low-speed concep : g ow h ac o elease, biocompa ibili y, and
cellula esponse. J Pe iodon ol. 2017;88(1):112–21.
19. Dohan DM, Chouk oun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi
J, e al. Pla ele - ich ib in (PRF): a second-gene a ion pla ele
concen a e. Pa II: pla ele - ela ed biologic ea u es. O al Su g
O al Med O al Pa hol O al Radiol Endod. 2006;101(3):e45-50.
20. Mi on RJ, Fujioka-Kobayashi M, Bisha a M, Zhang Y, He nandez
M, Chouk oun J. Pla ele - ich ib in and so issue wound healing:
a sys ema ic e iew. Tissue Eng Pa B Re . 2017;23(1):83–99.
21. Libe a i A, Al man DG, Te zla J, Mul ow C, Gø zsche PC, Ioan-
nidis JPA, e al. The PRISMA s a emen o epo ing sys ema ic
e iews and me a-analyses o s udies ha e alua e heal hca e
in e en ions: explana ion and elabo a ion. BMJ. 2009;339:b2700.
22. Higgins JPT, Al man DG, Go zsche PC, Juni P, Mohe D, Oxman
AD, e al. The coch ane collabo a ion’s ool o assessing isk o
bias in andomised ials. BMJ. 2011;343:d5928–d5928.
23. Cip iani A, Higgins JPT, Geddes JR, Salan i G. Concep ual and
echnical challenges in ne wo k me a-analysis. Ann In e n Med.
2013;159(2):130–7.
24. Reken S, S u z S, Kie e C, Böhle YB, Wiesele B. Assump ions
o mixed ea men compa isons in heal h echnology assessmen s
- challenges and possible s eps o p ac ical applica ion. PLoS
ONE. 2016;11(8):e0160712.
25. Salan i G. Indi ec and mixed- ea men compa ison, ne wo k, o
mul iple- ea men s me a-analysis: many names, many bene i s,
many conce ns o he nex gene a ion e idence syn hesis ool.
Res Syn h Me hods. 2012;3(2):80–97.
26. An onacci D, Caponio VCA, T oiano G, Pompeo MG, Gian eda
F, Canullo L. Facial scanning echnologies in he e a o digi al
wo k low: a sys ema ic e iew and ne wo k me a-analysis. J P os-
hodon Res. 2023;67(3):321–36.
27. Hu on B, Salan i G, Caldwell DM, Chaimani A, Schmid CH,
Came on C, e al. The PRISMA ex ension s a emen o epo -
ing o sys ema ic e iews inco po a ing ne wo k me a-analyses o
heal h ca e in e en ions: checklis and explana ions. Ann In e n
Med. 2015;162(11):777–84.
28. Puhan MA, Schünemann HJ, Mu ad MH, Li T, B igna dello-
Pe e sen R, Singh JA, e al. A g ade wo king g oup app oach
o a ing he quali y o ea men e ec es ima es om ne wo k
me a-analysis. BMJ. 2014;349:g5630.
29. Chaimani A, Higgins JPT, Ma idis D, Spy idonos P, Salan i
G. G aphical ools o ne wo k me a-analysis in STATA. PLoS
ONE. 2013;8(10):e76654.
30. Sha ma A, P adeep A . T ea men o 3-wall in abony de ec s
in pa ien s wi h ch onic pe iodon i is wi h au ologous pla ele -
ich ib in: a andomized con olled clinical ial. J Pe iodon ol.
2011;82(12):1705–12.
31. Tho a M, P adeep AR, Palla i B. Clinical e ec o au ologous
pla ele - ich ib in in he ea men o in a-bony de ec s: a con-
olled clinical ial. J Clin Pe iodon ol. 2011;38(10):925–32.
32. Joseph VR, Sam G, Amol NV. Clinical e alua ion o au ologous
pla ele ich ib in in ho izon al al eola bony de ec s. J Clin
Diagn Res. 2014;8(11):ZC43-47.
33. Ajwani H, She y S, Gopalak ishnan D, Ka ha iya R, Kulloli
A, Dolas RS, e al. Compa a i e e alua ion o pla ele - ich
ib in bioma e ial and open lap deb idemen in he ea men
o wo and h ee wall in abony de ec s. J In O al Heal h.
2015;7(4):32–7.
34. Bajaj P, Aga wal E, Rao NS, Naik SB, P adeep AR, Kal a N, e al.
Au ologous pla ele - ich ib in in he ea men o 3-wall in abony
de ec s in agg essi e pe iodon i is: a andomized con olled clini-
cal ial. J Pe iodon ol. 2017;88(11):1186–91.
35. Pa el GK, Gaekwad SS, Gujja i SK, Vee end a Kuma SC. Pla e-
le - ich ib in in egene a ion o in abony de ec s: a andomized
con olled ial. J Pe iodon ol. 2017;88(11):1192–9.
36. P adeep AR, Bajaj P, Rao NS, Aga wal E, Naik SB. Pla ele -
ich ib in combined wi h a po ous hyd oxyapa i e g a o
he ea men o 3-wall in abony de ec s in ch onic pe i-
odon i is: a andomized con olled clinical ial. J Pe iodon ol.
2017;88(12):1288–96.
37. Tho a M, Baghele ON, Rakhewa PS. Adjunc i e e ec o au olo-
gous pla ele - ich ib in in he ea men o in abony de ec s in
localized agg essi e pe iodon i is pa ien s: a andomized con-
olled spli -mou h clinical ial. In J Pe iodon ics Res o a i e
Den . 2017;37(6):302–9.
38. Ma hu A, Bains VK, Gup a V, Jhing an R, Singh GP. E alu-
a ion o in abony de ec s ea ed wi h pla ele - ich ib in o
au ogenous bone g a : a compa a i e analysis. Eu J Den .
2015;09(01):100–8.
39. Shah M, Pa el J, Da e D, Shah S. Compa a i e e alua ion o pla e-
le - ich ib in wi h demine alized eeze-d ied bone allog a in
pe iodon al in abony de ec s: a andomized con olled clinical
s udy. J Indian Soc Pe iodon ol. 2015;19(1):56–60.
40. Chadwick JK, Mills MP, Mealey BL. Clinical and adiog aphic
e alua ion o demine alized eeze-d ied bone allog a e sus
pla ele - ich ib in o he ea men o pe iodon al in abony
de ec s in humans. J Pe iodon ol. 2016;87(11):1253–60.
Odon ology
41. Gala S, Chand asheka KT, Mish a R, T ipa hi V, Aga wal R,
Gala A. Compa a i e e alua ion o pla ele - ich ib in and au og-
enous bone g a o he ea men o in abony de ec s in ch onic
pe iodon i is: clinical, adiological, and su gical een y. Indian J
Den Res. 2016;27(5):502.
42. Bansal C, Bha i V. E alua ion o e icacy o au ologous pla ele -
ich ib in wi h demine alized- eeze d ied bone allog a in he
ea men o pe iodon al in abony de ec s. J Indian Soc Pe iodon-
ol. 2013;17(3):361–6.
43. Elgendy EA, Abo Shady TE. Clinical and adiog aphic e alua ion
o nanoc ys alline hyd oxyapa i e wi h o wi hou pla ele - ich
ib in memb ane in he ea men o pe iodon al in abony de ec s.
J Indian Soc Pe iodon ol. 2015;19(1):61–5.
44. Aga wal A, Gup a ND, Jain A. Pla ele ich ib in combined wi h
decalci ied eeze-d ied bone allog a o he ea men o human
in abony pe iodon al de ec s: a andomized spli mou h clinical
ail. Ac a Odon ol Scand. 2016;74(1):36–43.
45. Naq i A, Gopalak ishnan D, Bhasin MT, Sha ma N, Haide K,
Ma ande S. compa a i e e alua ion o bioac i e glass pu y
and pla ele ich ib in in he ea men o human pe iodon al
in abony de ec s: a andomized con ol ial. J Clin Diagn Res.
2017;11(7):ZC09-ZC13.
46. Sezgin Y, U az A, Tane IL, Çulhaoğlu R. E ec s o pla ele -
ich ib in on healing o in a-bony de ec s ea ed wi h ano ganic
bo ine bone mine al. B az O al Res. 2017;31:e15.
47. Liu K, Huang Z, Chen Z, Han B, Ouyang X. T ea men o
pe iodon al in abony de ec s using bo ine po ous bone min-
e al and guided issue egene a ion wi h/wi hou pla ele - ich
ib in: a andomized con olled clinical ial. J Pe iodon ol.
2021;92(11):1546–53.
48. Paolan onio M, Di Tullio M, Gi audi M, Romano L, Secondi L,
Paolan onio G, e al. Pe iodon al egene a ion by leukocy e and
pla ele - ich ib in wi h au ogenous bone g a e sus enamel
ma ix de i a i e wi h au ogenous bone g a in he ea men o
pe iodon al in abony de ec s: a andomized non-in e io i y ial.
J Pe iodon ol. 2020;91(12):1595–608.
49. Bodha e GH, Kol e AP, Kol e RA, Shi ke PY. Clinical and adio-
g aphic e alua ion and compa ison o bioac i e bone alloplas
mo sels when used alone and in combina ion wi h pla ele - ich
ib in in he ea men o pe iodon al in abony de ec s-a and-
omized con olled ial. J Pe iodon ol. 2019;90(6):584–94.
50. Pham TAV. In abony de ec ea men wi h pla ele - ich ib in,
guided issue egene a ion and open- lap deb idemen : a and-
omized con olled ial. J E id Based Den P ac . 2021;21(3):
101545.
51. Us aoğlu G, Uğu Aydin Z, Özelçi F. Compa ison o GTR, T-PRF
and open- lap deb idemen in he ea men o in abony de ec s
wi h endo-pe io lesions: a andomized con olled ial. Med O al
Pa ol O al Ci Bucal. 2020;25(1):e117–23.
52. Panda S, Sanka i M, Sa pa hy A, Jayakuma D, Mozza i M, Mo -
ella o C, e al. Adjunc i e e ec o au ologus pla ele - ich ib in
o ba ie memb ane in he ea men o pe iodon al in abony
de ec s. Jou nal o C anio acial Su ge y. 2016;27(3):691.
53. P adeep AR, Rao NS, Aga wal E, Bajaj P, Kuma i M, Naik SB.
Compa a i e e alua ion o au ologous pla ele - ich ib in and
pla ele - ich plasma in he ea men o 3-wall in abony de ec s
in ch onic pe iodon i is: a andomized con olled clinical ial. J
Pe iodon ol. 2012;83(12):1499–507.
54. Gup a SJ, Jhing an R, Gup a V, Bains VK, Madan R, Riz i I.
E icacy o pla ele - ich ib in s. enamel ma ix de i a i e in
he ea men o pe iodon al in abony de ec s: a clinical and
cone beam compu ed omog aphy s udy. J In Acad Pe iodon ol.
2014;16(3):86–96.
55. Aydemi Tu kal H, Demi e S, Dolgun A, Keceli HG. E alua ion
o he adjunc i e e ec o pla ele - ich ib in o enamel ma ix
de i a i e in he ea men o in abony de ec s. Six-mon h esul s
o a andomized, spli -mou h, con olled clinical s udy. J Clin
Pe iodon ol. 2016;43(11):955–64.
56. P adeep AR, Nagpal K, Ka eka S, Pa naik K, Naik SB, Gu u-
p asad CN. Pla ele - ich ib in wi h 1% me o min o he ea -
men o in abony de ec s in ch onic pe iodon i is: a andomized
con olled clinical ial. J Pe iodon ol. 2015;86(6):729–37.
57. Kano iya D, P adeep AR, Singhal S, Ga g V, Gu up asad CN.
Syne gis ic app oach using pla ele - ich ib in and 1% alend ona e
o in abony de ec ea men in ch onic pe iodon i is: a and-
omized clinical ial. J Pe iodon ol. 2016;87(12):1427–35.
58. Ma ande SS, Kuma i M, P adeep AR, Singh SP, Suke DK,
Gu up asad CN. Pla ele - ich ib in combined wi h 12% a o -
as a in o ea men o in abony de ec s in ch onic pe i-
odon i is: a andomized con olled clinical ial. J Pe iodon ol.
2016;87(9):1039–46.
59. P adeep A , Ga g V, Kano iya D, Singhal S. Pla ele - ich ib in
wi h 12 osu as a in o ea men o in abony de ec s in ch onic
pe iodon i is: a andomized con olled clinical ial. J Pe iodon ol.
2016;87(12):1468–73.
60. Caponio VCA, Baca-González L, González-Se ano J, To es J,
López-Pin o RM. E ec o he use o pla ele concen a es on
new bone o ma ion in al eola idge p ese a ion: a sys ema ic
e iew, me a-analysis, and ial sequen ial analysis. Clin O al
In es ig. 2023;27(8):4131–46.
Publishe 's No e Sp inge Na u e emains neu al wi h ega d o
ju isdic ional claims in published maps and ins i u ional a ilia ions.
Au ho s and A ilia ions
FábioF ançaViei aeSil a1 · LuisChauca‑Bajaña2 · Vi oCa loAlbe oCaponio3 ·
Ka eelendAnd einaSegu aCue a4 · By onVelasquez‑Ron5 · Ma iaElenaPadín‑I uegas6 ·
LaysLamolhaAlmeida7· Alejand oIsmaelLo enzo‑Pouso8 · JoséManuelSuá ez‑Peña anda1 ·
Ma ioPé ez‑Sayáns9
* José Manuel Suá ez-Peña anda
[email p o ec ed]
Fábio F ança Viei a e Sil a
d abio anca[email p o ec ed]
Luis Chauca-Bajaña
[email p o ec ed]; luisc[email p o ec ed]
Vi o Ca lo Albe o Caponio
[email p o ec ed]
Ka eelend And eina Segu a Cue a
[email p o ec ed]
By on Velasquez-Ron
by on. elasq[email p o ec ed]; d [email p o ec ed]

Odon ology
Ma ia Elena Padín-I uegas
[email p o ec ed]
Lays Lamolha Almeida
[email p o ec ed]
Alejand o Ismael Lo enzo-Pouso
ale[email p o ec ed]
Ma io Pé ez-Sayáns
[email p o ec ed]
1 Facul y o Medicine andDen is y, O al Su ge y
andImplan ology Uni (MedO alRes, O al Medicine,
Uni e sidade de San iago de Compos ela. Heal h Resea ch
Ins i u e o San iago de Compos ela (IDIS), San iago
de Compos ela Uni e si y Hospi al Complex, Rúa da
Choupana, S/N, 15706San iagodeCompos ela, ACo uña,
Spain
2 Pe iodon ics andImplan ology O al Resea ch. College
Den is y, Ecuado . Facul y o Medicine andDen is y,
Uni e si y o Guayaquil, O al Medicine, O al Su ge y
andImplan ology Uni , Uni e sidade de San iago de
Compos ela, San iagodeCompos ela, ACo uña, Spain
3 Depa men o Clinical andExpe imen al Medicine,
Uni e si y o Foggia, 71100Foggia, I aly
4 O al Su ge y, Depa men o Den is y, Uni e si y
o Guayaquil, Qui o-Ecuado , Ecuado
5 Den al P os hesis Depa men Resea ch. College Den is y,
Uni e si y o  heAme icas. UDLA. A , Colon y 6 de
Diciemb e, Campus Colón, Qui o-Ecuado , Ecuado
6 Human Ana omy andEmb yology A ea, Depa men
o Func ional Biology andHeal h Sciences, Facul y
o Physio he apy, Uni e si y o Vigo, 36001Pon e ed a,
Spain
7 Depa men o Den al Medicine, Fede al Fluminense
Uni e si y, RiodeJanei o28625650, B azil
8 O al Medicine, O al Su ge y andImplan ology Uni
(MedO alRes), Facul y o Medicine andDen is y, Uni e si y
o San iago de Compos ela, 15782San iagodeCompos ela,
Spain
9 Facul y o Medicine andDen is y, O al Su ge y
andImplan ology Uni (MedO alRes, O al Medicine,
Uni e sidade de San iago de Compos ela. Heal h Resea ch
Ins i u e o San iago de Compos ela (IDIS), Ins i u o de los
Ma e iales de San iago de Compos ela (iMATUS), A enida
Do Mes e Ma eo, 25, 15782San iagodeCompos ela,
ACo uña, Spain