The effects of gardening on quality of life

SYSTEMATIC REVIEW

̈ 333

Massimo Del Fabbro, Stefano Corbella, Silvio Taschieri, Luca Francetti, Roberto Weinstein

Autologous platelet concentrate for post-extraction
socket healing: A systematic review
Massimo Del Fabbro,
BSc, PhD

Key words

platelet concentrates, socket healing, systematic review, tooth sockete

Background: Autologous platelet concentrates are claimed to enhance hard and soft tissue healing
due to the considerable amount of growth factors that are released after application in the surgical site. However, their actual efficacy for improving tissue healing and regeneration in oral surgery
applications is controversial. Tooth extraction socket healing represents a proper model to study the
effect of autologous platelet-enriched preparations due to the concomitant occurrence of different
processes of both hard and soft tissue healing.
Purpose: To evaluate the efficacy of platelet concentrates for alveolar socket healing after tooth
extraction, by conducting a systematic review.
Materials and methods: Medline, Embase and Cochrane Central Register of Controlled Trials were
searched using a combination of specific search terms. The last electronic search was performed on
15 June, 2014. Manual searching of the relevant journals and of the reference lists of reviews and all
identified randomised controlled trials was also performed. Randomised controlled trials evaluating
the effect of a platelet concentrate on fresh extraction sockets were included. Further inclusion criteria
were that at least 10 patients were treated (at least 5 per group) and there was a minimum follow-up
duration of 3 months. Primary outcomes were postoperative complications, patient satisfaction and
postoperative discomfort. Secondary outcomes were any clinical, radiographic, histological and histomorphometric variables used to assess hard and soft tissue healing. Assessment of the methodological
quality of the trials was made. Results were expressed as fixed-effects models using mean differences

for continuous outcomes and risk ratios for dichotomous outcomes, with 95% confidence intervals (CI).
Results: The initial search yielded 476 articles. After the screening process, six articles met the inclusion criteria (199 teeth in 156 patients). Three studies were considered at high risk of bias, two at
medium risk and one at low risk. A large heterogeneity in study characteristics and outcome variables
used to assess hard tissue healing was observed. A meta-analyses of two studies reporting histomorphometric evaluation of bone biopsies at 3 months’ follow-up showed greater bone formation when
platelet concentrates were used, as compared to control cases (P <0.001; mean difference 20.41%,
95% C.I. 13.29%, 27.52%). Beneficial effects of platelet concentrates were generally but not systematically reported in most studies, in particular when considering the effects on soft tissue healing
and the patient’s reported postoperative symptoms like pain and swelling, although no meta-analysis
could be done for such parameters.
Conclusions: Although the results of the meta-analysis of the present review are suggestive for a
positive effect of platelet concentrates on bone formation in post-extraction sockets, due to the

Eur J Oral Implantol 2014;7(4):333–344

Università degli Studi di
Milano, Department of Biomedical, Surgical and Dental
Sciences, Research Centre
In Oral Health, Milan, Italy;
IRCCS Istituto Ortopedico
Galeazzi, Milan, Italy

Stefano Corbella,
DDS, PhD
Private practice, Como,
Italy; Università degli Studi
di Milano, Department of
Biomedical, Surgical and
Dental Sciences, Research
Centre In Oral Implantology,
Milan, Italy

Silvio Taschieri, MD,
DDS
Università degli Studi di
Milano, Department of Biomedical, Surgical and Dental
Sciences, Research Centre
In Oral Health, Milan, Italy;
IRCCS Istituto Ortopedico
Galeazzi, Milan, Italy

Luca Francetti, MD,
DDS
Università degli Studi di
Milano, Department of
Biomedical, Surgical and
Dental Sciences, Research
Centre In Oral Implantology,
Milan, Italy;
IRCCS Istituto Ortopedico
Galeazzi, Milan, Italy

Roberto Weinstein,
MD, DDS
Università degli Studi di
Milano, Department of
Biomedical, Surgical and
Dental Sciences, Research
Centre In Oral Health and
Research Centre In Oral
Implantology, Milan, Italy;
IRCCS Istituto Ortopedico

Galeazzi, Milan, Italy


334 ̈

Correspondence to:
Massimo Del Fabbro
IRCCS Istituto Ortopedico
Galeazzi
Via R. Galeazzi, 4
20161 – Milan
Italy
Tel: +39 02 50319950
Fax: + 39 02 50319960
Email: massimo.delfabbro@
unimi.it

Del Fabbro et al

Socket healing using platelet concentrates

limited amount and quality of the available evidence, they need to be cautiously interpreted. A
standardisation of the experimental design is necessary for a better understanding of the true effects
of the use of platelet concentrates for enhancing post-extraction socket healing.
Conflict of interest statement: The authors declare they have no conflicts of interest.

̈ Introduction
Tooth extraction is performed for a wide variety of
reasons, such as: tooth decay with extensive destruction of tooth structure, which makes the tooth non
restorable; periodontal disease with loss of tooth

support and mobility; trauma; root fracture; acute
infection; impaction, or for orthodontic reasons1-3.
Post-extraction socket healing causes many important alterations in the volume and shape of the
socket itself, which are the results of concomitant
mechanisms of bone resorption and apposition4-6. A
succession of events leading to the healing of the alveolar socket after extraction was described by several histological studies7-9. The greatest amount of
bone loss occurs in the horizontal dimension, mainly
on the facial aspect, causing narrowing of the ridge.
A consistent vertical reduction also takes place,
more pronounced at the buccal side4,6,10. Bone volume decrease after tooth extraction can have an
important effect on the possibility of an effective
substitution with dental implants. Insufficient bone
volume in the site can complicate implant insertion,
creating the need for a bone grafting procedure
before or immediately after implant placement11,12.
Many socket preservation procedures with the
use of different biomaterials have been proposed
by scientific literature5,13,14. Autologous platelet
concentrates are a group of biomaterials derived
from human blood15. Several commercial systems
for preparing autologous platelet concentrates are
available today, which allow the preparation of
products with different composition and biological
activity, but all are characterised by a concentration
of platelets higher than in the systemic blood. Platelet concentrates have been classified into four main
categories, according to their fibrin matrix density
and their content in leukocytes15. The three types of
platelet concentrates mostly used in the clinical setting are the following: (i) platelet-rich plasma (PRP,

Eur J Oral Implantol 2014;7(4):333–344

also defined as L-PRP15), which is characterised by
the presence of leukocytes, a high platelet concentration (up to 5 to 8 times the baseline value). It is
prepared from anti-coagulated blood undergoing a
double centrifugation step and requires an activator before use16; (ii) plasma rich in growth factors
(PRGF, also defined P-PRP15) is characterised by the
absence of leukocytes, a modest increase in platelet
concentration (2 to 3 times the baseline value). It is
prepared from anti-coagulated blood undergoing a
single centrifugation step, and requires an activator before use17; (iii) platelet-rich fibrin (PRF, also
defined L-PRF15) is characterised by the presence of
most platelet and leukocytes in a dense fibrin matrix
that does not require an activator before use. It is
prepared from non-anti-coagulated blood undergoing a single centrifugation step18.
Tooth extraction socket healing represents a
proper model to study the effect of autologous
platelet-enriched preparations in wound healing
because it is the ending point of different simultaneous processes of both hard and soft tissue healing in
a septic environment, like the oral cavity7-8. Scientific
literature however is rather controversial regarding
the true effect of autologous platelet concentrates
in the healing process. In fact, some studies have
shown the positive effect of haemocomponents in
enhancing tissue healing after bone grafting procedures, like maxillary sinus augmentation or the treatment of bony defects16,19-21, while others reported
no significant effects of platelet concentrates22.
In oral surgery applications, though most studies
report a beneficial effect on soft tissue healing, their
actual effect in enhancing bone regeneration is still
unproven19-21.
The aim of the present systematic review was

to evaluate the efficacy of platelet concentrates
for enhancing alveolar socket healing after tooth
extraction. The PICO question leading the review
was: “In patients undergoing tooth extraction, does


Del Fabbro et al

the local application of autologous platelet concentrate improve clinical, radiographic and histological
outcomes related to socket healing as compared to
control?”

̈ Materials and methods
This study is reported by following the PRISMA
statement ( />
̈ Eligibility criteria
Only randomised controlled trials of both parallel and
split-mouth design assessing the efficacy of platelet
concentrates for healing and regeneration of hard
tissues in patients undergoing tooth extraction were
included. Studies were included only if a test group
using platelet concentrates was compared with a
control group in which platelet concentrates were
not used. Platelet concentrates could be used alone
or in combination with other materials, but for study
inclusion they had to be the only difference between
test and control. Any type of platelet concentrate was
to be included. Randomised controlled trials (RCTs)
treating at least 10 patients (at least 5 patients per
group) were considered. Studies were included if the

follow-up duration was at least 3 months.

̈ Search strategy
A literature search was carried out on electronic
databases (MEDLINE, EMBASE, Cochrane Central
Register of Controlled Trials), using an ad hoc created
search string: (‘platelet-rich plasma’ OR ‘autologous
platelet concentrates’ OR ‘platelet growth factors’
OR ‘platelet-rich fibrin’ OR ‘PRP’ OR ‘PRGF’ OR
‘PRF’) AND (‘oral surgery’ OR ‘extraction socket’ OR
‘post-extraction socket’ OR ‘socket preservation’ OR
‘tooth extraction’ OR ‘third molar surgery’). The last
electronic search was performed on 15 June, 2014.
A further hand search was performed on the following journals in the field of dentistry and of oral and
maxillofacial surgery: British Dental Journal; British
Journal of Oral and Maxillofacial Surgery; Clinical
Implant Dentistry and Related Research; Clinical
Oral Implants Research; Clinical Oral Investigations;
European Journal of Oral Implantology; European

Socket healing using platelet concentrates

Journal of Oral Sciences; Implant Dentistry; International Journal of Oral and Maxillofacial Implants;
International Journal of Oral and Maxillofacial
Surgery; International Journal of Periodontics and
Restorative Dentistry; Journal of Clinical Periodontology; Journal of Dental Research; Journal of Dentistry; Journal of Maxillofacial and Oral Surgery;
Journal of Oral and Maxillofacial Surgery; Journal
of Periodontal Research; Journal of Periodontology;
and Oral Surgery Oral Medicine Oral Pathology
Oral Radiology and Endodontology.

The reference list of all identified RCTs and of relevant reviews was also scanned for possible additional
studies. Online databases providing information
about current clinical trials in progress were checked
( terwatch.
com/clinicaltrials/; http:// www.clinicalconnection.
com/). No language restriction was placed.

̈ Data collection
The titles and abstracts of the retrieved articles were
screened independently by two reviewers (MDF, SC)
to identify all eligible studies apparently meeting the
inclusion criteria. When the abstract was not available or did not provide sufficient data to allow unequivocal evaluation, the full text was obtained and
checked. Publications that did not meet the selection
criteria were excluded. Disagreements were resolved
by discussion. The full text of all the eligible articles
was obtained and the characteristics of the studies were examined by the reviewers to either confirm study inclusion for data analysis or to exclude
the study. Relevant data were extracted from the
included studies and analysed.
Primary outcome measures were:
t
any complication and adverse event (e.g. alveolar
osteitis, acutely infected or inflamed alveolus)
t
patient satisfaction (through a questionnaire)
t
postoperative discomfort/quality of life (e.g.
postoperative pain on a visual analogue scale
[VAS], swelling).
Secondary outcome measures were:
t
radiographic evaluation of bone healing (e.g.
assessment of bone density or trabecular bone
pattern at the extraction site)

Eur J Oral Implantol 2014;7(4):333–344

̈ 335


Identification

336 ̈

Del Fabbro et al

Records identified through database dearching
(n = 474)

Socket healing using platelet concentrates

Additional records identified
through other sources
(n = 11)

Records screened
(n = 476)

Records excluded
(n = 454)

Screening

Full-text articles assessed
for eligibility

(n = 22)

articles excluded, with reasons
(n = 5 not randomized; n = 6
too short follow-up; n = 2
platelet concentrate not the
only difference; n = 1 not
pertinent with the review aims;
n = 1 multiple sites treated in
some patients; n = 1 unretrievable

Eligibility

Studies included in the
qualitative synthesis
(n = 6)

Full-text articles excluded from
quantitative synthesis
(n = 4)

Included

Records after duplicates removed
(n = 476)

Studies included in
quantitative synthesis
(meta-analysis) (n = 2)

criteria: randomisation method; concealed allocation
of treatment; sample size calculation; completeness
of information on reasons for withdrawal by trial
group; definition of exclusion/inclusion criteria; comparability of control and test groups at entry; calibration and blinding of outcome assessors; blinding of
patients. All these criteria were judged as adequate/
inadequate/unclear. The authors of the identified
studies were contacted for clarification or to provide
missing information.
In order to summarise the validity of the studies,
they were grouped into the following categories:
low risk of bias (plausible bias unlikely to seriously
alter the results) if all quality criteria were judged
adequate; moderate risk of bias (plausible bias that
raises some doubt about the results) if one or more
criteria were considered unclear; high risk of bias
(plausible bias that seriously weakens confidence
in the results) if one or more criteria were judged
inadequate. Criteria for assessing the risk of bias of
RCTs in the present review were adapted from the
guidelines reported in the Cochrane Handbook for
Systematic Reviews of Interventions24. Any disagreement between the two reviewers was resolved
by discussion. If agreement was not obtained, a third
reviewer was consulted (ST).

̈ Data analysis
Fig 1

Diagram of article selection process.

t
histomorphometric evaluation of bone healing

(e.g. bone volume percentage)
t
clinical/radiographic evaluation of marginal bone
remodelling (e.g. bone height at the vestibular
and lingual/palatal aspect and bone width at the
extraction region)
t
clinical evaluation of soft tissue healing (e.g.
using tools like the Landry et al index23).

̈ Risk of bias assessment
The methodological quality of the included studies
was evaluated independently and in duplicate by
two reviewers (MDF, SC) as part of the data extraction process. The risk of bias of the included trials
was assessed based on the following eight quality

Eur J Oral Implantol 2014;7(4):333–344

Heterogeneity among studies for the estimates of
treatment effects was assessed using Cochran’s test
for heterogeneity, considering it significant if P <0.1.
The quantification of the heterogeneity was calculated with I2 statistics, which describes the percentage total variation across studies that is due to heterogeneity rather than chance. If I2 was over 50% it
was considered significant (substantial heterogeneity).
For each trial, for dichotomous outcomes (e.g.
postoperative alveolar osteitis, yes/no), the estimate
of effect of an intervention was expressed as risk
ratios together with 95% confidence intervals. For
continuous outcomes (e.g. % of newly formed bone,
alveolar bone height and width change), mean differences (change score) along with 95% confidence
intervals (CIs) were used to summarise data for each
treatment group. The statistical analysis unit was the
patient and not the tooth.

Del Fabbro et al

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Socket healing using platelet concentrates

Table 1 Main characteristics of the included studies (pa = parallel; sm = split mouth).
Author, publication year

Study
design

Study
setting

Sponsored
study

Country

No.
patients

Mean age
(range), y

No. teeth

Anitua, 199943

RCT
(pa)

PrC

NR

Spain

20

41.5 (35–55)

10

Alissa et al,
201044

RCT
(pa)

Univ

no

UK

23

30.5 (20–52)

Ogundipe et
al, 201145

RCT
(pa)

Univ

NR

Nigeria

60

Célio-Mariano
et al, 201246

RCT
(sm)

Univ

NR

Brazil

Kutkut et al,

201247

RCT
(pa)

Univ

pu

Girish Rao et
al, 201348

RCT
(sm)

Univ

pu

Test

Ctr

Intervention

FU,
weeks

Test

Ctr

10

PRGF ±
ABG

none ±
ABG

10 to 16

15

14

PRP

none

12

24.7 (19–35)

30

30

PRP

none

16

15

NR (18–22)

15

15

PRP

none

6 mo

USA

16

52 (19–75)

8

8

PRP +
MGCSH

collagen

12

India

22

NR

22

22

PRF

none

6 mo

Ctr = control; PRGF = plasma rich in growth factors; PRP = platelet-rich plasma; ABG = autogenous bone; MGCSH = medical-grade calcium sulfate hemihydrate; FU = follow-up; y = years; NR = not reported; PrC = Private Centre; Univ = University; pu = public sponsor

It was planned that sensitivity analysis should be
performed to evaluate the effect of the risk of bias on
the overall estimates of effect. Meta-analyses were
performed only with studies with similar comparisons
reporting the same outcome measures. Risk ratios
were to be combined for dichotomous data, and
mean differences for continuous data using randomeffects models if at least four studies could be included

in the meta-analysis, while if there would be less than
four studies then a fixed effects model was chosen.
The software RevMan (Review Manager Version 5.3,
2014; The Nordic Cochrane Center, The Cochrane
Collaboration, Copenhagen, Denmark) was used for
meta-analysis computations. Data from split-mouth
and parallel group studies were to be combined25.
The appropriate standard errors were to be estimated
where these were not presented in the trial reports26.
The generic inverse variance procedure in RevMan
5.2 was to be used to combine these two subgroups
in the analyses. Furthermore, for the effect of the
follow-up duration (<4 months and ≥4 months) and
of the type of platelet concentrate used (platelet-rich
plasma (PRP), platelet-rich fibrin (PRF) or plasma rich
in growth factors (PRGF)), evaluation was planned by
means of subgroup analyses.

̈ Results
The article selection process is presented in Fig 1.
The electronic search retrieved 474 articles while 11

studies were identified from the manual search. After
the removal of duplicates, 476 articles resulted and
were screened. Twenty-two full-text articles were
assessed for eligibility27-48. A total of 16 studies were
excluded after full-text evaluation: 5 studies because
the treatment was not allocated randomly27-31; 2
studies because platelet concentrate was not the
only difference between test and control group32-33;

1 study because the full text was unretrievable34; 1
study because it was not pertinent with the aims of
the review35; 1 study because some patients had
multiple extracted teeth considered in the test and
control group36; and other 6 studies due to a too
short follow-up37-42. Finally, a total of 6 randomised
controlled trials were included43-48.
One article43 reported of a hybrid split-mouth/
parallel study design in which 20 patients needing
a single tooth extraction were randomly assigned to
either the test or the control group, while in three
additional patients multiple extractions were performed in different mouth regions so that plasma
rich in growth factors (PRGF) was used in one area
but not in any other. Therefore these three patients
were excluded from the analysis and only the parallel
branch of the study was considered.
The main characteristics of the included studies and the outcome measures are summarised in
Table 1 and Table 2.
A total of 199 teeth in 156 patients were included
in this review. One hundred teeth belonged to the
test group and 99 to the control group. Four RCTs

Eur J Oral Implantol 2014;7(4):333–344


338 ̈

Del Fabbro et al

Socket healing using platelet concentrates

Table 2 Type of extraction and outcome variables of the included studies.
Author,
publication year

Tooth type / reason for extraction

Outcome variables

Evaluation methods

Effect of platelet concentrate as
reported in the study

Anitua, 199943

Various tooth
types / untreatable
tooth with vertical
fracture or severe
periodontal disease

Soft tissue healing
Hard tissue healing

– Clinical assessment
– Histological analysis
– Histomorphometric analysis

In PRGF group better epithelialisation,

more mature bone and better organised trabeculae than control group (no
quantitative evaluation provided)

Alissa et al,
201044

Various tooth
types / mostly
caries (60.9%) and
endodontic failure
(21.7%)

Incidence of complications
Post–op quality of life
Soft tissue healing
Hard tissue healing

– VAS for pain evaluation; 1–week
questionnaire for swelling, bruising,
bleeding, bad taste, food stagnation, satisfaction, analgesics taken
– Socket complications: alveolar osteitis, infection, inflammation
– Soft tissue healing index of Landry
et al23
– Radiological analysis (periapical
radiographs)
– Histomorphometric analysis

In PRP group less pain & analgesic
consumption in the first 2–3 days
(P = 0.02 to 0.04), borderline less

complications (P = 0.06) and improved
hard (P = 0.01) and soft tissue healing
(P = 0.03) than control group

Ogundipe et al,
201145

Mandibular third
molars / impaction

Post–op quality of life
Hard tissue healing

– VAS for pain evaluation, difference in facial swelling and mouth
opening
– Radiographic evaluation of bone
healing (mod. method used by Kelley et al49)

In PRP group less pain (P <0.05),
swelling and trismus (NSD); enhanced
and faster bone healing (NSD) than
control group

Célio–Mariano
et al, 201246

Mandibular third
molars / impaction

Hard tissue healing

Radiographic bone density (periapical
radiography)

In PRP group accelerated alveolar bone
formation than control group
(P <0.01) until 3rd month, NSD at 6th
month

Kutkut et al,
201247

Maxillary central
and lateral incisors,
maxillary canines,
maxillary and mandibular premolars

Soft tissue healing
Hard tissue healing

– Clinical assessment of mesial, distal,
buccal, lingual changes
– Radiographic assessment of bone
density in the extraction site and
mesial and distal bone resorption
– Vertical and horizontal socket
dimensions measured on casts made
from alginate impression at baseline
and at 3 months follow–up, using a
20 mm implant spacer probe

– Histomorphometric analysis of trephined samples taken at 3 months

In PRP group limited bone resorption
after tooth extraction (NSD); higher
vital bone % (P <0.05); faster soft
tissue closure (not quantified) than
control group

Girish Rao et al,
201348

Mandibular third
molars / impaction

Hard tissue healing

Radiographic assessment of optical
density within the socket (RVG, Radio
Visio–Graphic Analysis)

In PRF group non significantly higher
mean pixels at all time intervals than
control group

CT = computerised tomography; VAS = Visual Analogue Scale; NSD = not significantly different

had a parallel design and two RCTs a split-mouth
design. In all studies there was a fairly balanced ratio
between test and control cases.
Methods for the concentrate preparation

adopted in the different studies are detailed in
Table 3. There was a great heterogeneity in the
protocol for preparing the platelet concentrates, in
the type of platelet concentrate used, and there
was a relative lack of information about the actual

Eur J Oral Implantol 2014;7(4):333–344

increase of platelet concentration after the centrifugation process.

̈ Risk of bias assessment
Risk of bias assessment results are presented in
Table 4. Only one study was classified at low risk of
bias44, two at medium risk43,45, and three at high
risk of bias46-48.


Del Fabbro et al

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Socket healing using platelet concentrates

Table 3 Methods for platelet concentrates preparation.
Author,
publication
year

Centrifugation system, manufacturer

Volume
of blood
drawn, ml

Anticoagulant
solution

Centrifugation
parameters:
No.; speed; time

Increase
of platelet
concentration
from baseline

Activator

Anitua, 199943

PRGF System, BTI Biotechnology Institute, Vitoria, Alava, Spain

10–20

10% trisodium
citrate

1×; 160 g; 6 min

2–3 fold

Calcium
chloride

Alissa et al,
20144

– PCCSTM II, 3i Implant Innovations,
Palm Beach Gardens, Florida, USA
– Bench-top centrifuge (IEC Model
I-703A, International Equipment Company, Needham Heig hts, MA, USA)

27

Citrate dextrose

1×; 3200 rpm;
12 min

NR

Autologous
thrombin

Ogundipe et
al, 201145

NR

10

NR

NR; NR; NR

NR

Calcium
chloride

Célio-Mariano
et al, 201246

NR

25

3.2% trisodium
citrate

1×; 160 g;
20 min + 1×;
400 g; 15 min

3–5 fold

Calcium
chloride

Kutkut et al,

201247

NR

5

10% trisodium
citrate

NR; NR; 10 min

NR

NR

Girish Rao et
al, 201348

NR

9

Acidulated citrate
dextrose

1×; 360–400 rpm;
20 min

up to 4 fold

Calcium
gluconate

min = minutes; NR = not reported; rpm = round per minute

Table 4 Quality assessment of the included studies.
Author, publication year

Study
type

Randomisation
method

Concealed
allocation
of treatment

Sample
size calculation

Completeness of
information on
dropouts

Definition of
inclusion /
exclusion
criteria

Comparability of
groups at
entry

Calibration
/ blinding
of assessors

Blinding
of patients

Risk of
bias

Anitua, 199943

parallel

a

u

i

a

a

a

a

NA

M

Alissa et al,
201044

parallel

a

a

a

a

a

a

a

NA

L

Ogundipe et al,

201145

parallel

a

a

i

a

a

a

a

NA

M

Célio-Mariano
et al, 201246

splitmouth

u

u

i

a

a

a

u

i

H

Kutkut et al,
201247

parallel

a

i

i

a

a

u

i

NA

H

Girish Rao et al,
201348

splitmouth

u

u

u

a

a

a

a

u

H

a = adequate; i = inadequate; u = unclear; NA = not applicable; H = high; M = medium; L = low

̈ Primary outcome measures
Complications/adverse events
Alissa et al44 evaluated socket complications on
21 out of 27 patients. Healing was uneventful in
18 patients with 24 extraction sites, while 3 patients
with three extraction sites developed 2 alveolar
osteitis and 1 acutely inflamed alveolus, all in the
control group44. The difference between groups was

borderline significant (P = 0.06). Ogundipe et al45
declared they recorded intraoperative complications
but did not report them in the results. The authors
were contacted to obtain such information but they
provided no answer.
None of the other studies accounted for intrasurgical or postsurgical complications.

Eur J Oral Implantol 2014;7(4):333–344


340 ̈

Fig 2

Del Fabbro et al

Socket healing using platelet concentrates

Meta-analysis of the studies presenting histomorphometric evaluation of bone formation. Outcome: percentage of bone tissue.

Quality of life
Postoperative quality of life was evaluated in one
study using a modified health-related quality of life
questionnaire that assessed patient perception of
recovery in four areas: pain; oral function; general
activity; and other postoperative symptoms44. The
study reported significant positive effects of platelet
concentrate only for the presence of bad taste or bad
smell in the mouth44.

Pain
Pain levels in the first week after surgery were
assessed using a Visual Analogue Scale (VAS) in two
studies44,45. These studies reported a significantly
lower pain level in the test group in the first postoperative week, indicating a beneficial effect of platelet
concentrates in reducing pain perception postoperatively44,45. However, due to the non-homogeneity of data provided that prevented comparison
among these two studies, no meta-analysis could
be performed for pain assessment. In fact one study
presented VAS data using box-and-whiskers plot44,
the other used mean values but standard deviations
were not provided45. We asked authors to provide
missing information but received no answer. None of
the other included studies evaluated postoperative
pain or quality of life.

̈ Secondary outcome measures
Hard tissue healing
Different techniques and methods were used to

evaluate hard tissue healing. Histological analysis
was performed in three studies, all of which reported
a better bone quality in biopsies retrieved from sites
treated with platelet concentrates, as compared to
control sites43,44,47. Two of these studies also pro-

Eur J Oral Implantol 2014;7(4):333–344

vided histomorphometric data on bone volume percentage, that allowed a meta-analysis to be performed44,47. A significantly greater proportion of
new bone was found in sites treated with platelet
concentrate as compared to controls, after a followup of 3 months (P <0.01, mean difference 20.41%,
95% C.I. 13.29%, 27.52%) (Fig 2)44,47.
Radiographic evaluation (through periapical radiographs, CT scans and panoramic radiographs) was
carried out in five studies44-48.
Alissa et al44 evaluated trabecular bone pattern at
socket level using both a subjective evaluation and an
automated texture analysis of periapical radiographs
at 12 weeks after extraction. The results of the subjective evaluation showed a significantly better outcome
for patients treated using PRP while the outcome of
the automated assessment, though in favour of the
PRP group, did not achieve significance44.
Ogundipe et al45 radiographically evaluated
socket healing after extraction of mandibular third
molar by using scores for lamina dura, overall density
and trabecular pattern, and a modification of the
method used by Kelley et al49. They found better
scores among patients in the PRP group for all of
these outcome variables, although the difference
was not statistically significant45.
Célio-Mariano et al46 radiographically evaluated

the change in bone density at 1 week, and at 2, 3
and 6 months after impacted third molar surgery in
a split-mouth study. They found faster bone formation in sockets treated with platelet concentrate, the
difference between groups being significant at 1, 2
and 3 months46.
In the study by Kutkut et al47, radiographic
assessment for bone resorption at mesial and distal
sites showed non significantly lower values at the
test sites after 3 months. They also reported that
“the bone regenerated in the extraction sites showed
more density in the test group as visually compared


Del Fabbro et al

to control group” but did not quantify such a statement nor provide statistical evaluation47. In the same
study, linear measurement of alveolar crest width
and height was performed on casts made from alginate impression at baseline and at 3 months’ followup, using a 20 mm implant spacer probe, showing no
significant difference between groups47.
Girish Rao et al48 radiographically evaluated
optical density within the socket using a softwaremediated Radio-Visio-Graphic (RVG) analysis that
allowed measurement of the number of pixels in the
residual cavity, which was considered proportional to
the size of the defect48. The results did not reveal a
statistically significant higher mean in the test group
as compared to control group, at all time intervals.
Due to differences in assessment methodology,
no meta-analysis could be done among these studies
for radiographic outcomes.

Soft tissue healing
Three studies reported data about soft tissue healing43,44,47. Anitua et al43 evaluated epithelialisation
clinically and histologically, and connective tissue
formation histologically at the defect site.
Alissa et al44 used the healing index described by
Landry and coworkers23, assessing healing trough
parameters as tissue colour, epithelialisation of
wound margins, bleeding on palpation, granulation
and suppuration.
Kutkut et al47 assessed soft tissue appearance and
the presence of infection and symptoms, reporting
no significant effect of platelet concentrates on soft
tissues47. Conversely, the other two articles found
a significant positive effect of the use of platelet
concentrate43,44.
Given the heterogeneity among parameters,
no meta-analysis was done to evaluate the effect
of platelet concentrates on soft tissue healing after
tooth extraction.

̈ Discussion
The present systematic review aimed at evaluating
the efficacy of a platelet-rich preparation in enhancing the healing of an alveolar socket after tooth
extraction.

Socket healing using platelet concentrates

With respect to a previous systematic review,
the present study reports updated results confirming, in general, the uncertainty regarding the
actual effect of platelet concentrates on socket

healing50. In fact, though most of the included
studies reported a positive effect of platelet concentrates, major limitations have to be considered;
firstly, the heterogeneity of the outcome variables,
of the method(s) chosen for socket healing assessment. No meta-analysis could be performed for
most of the outcome measures, for which only a
qualitative description was provided. Among the
most important confounding factors, there is the
indication for extraction, which can have a profound effect on the healing pattern of the alveolar
socket5,14. Due to the heterogeneity of outcome
variables among the included studies, the effect of
such a factor could not be explored. None of the
included studies reported data about socket healing for infected teeth. Only the study by Girish-Rao
et al48 excluded “patients with dental infection of
bone, active gingivitis or periodontitis”. Although
this variable would have increased the heterogeneity of the studies, it would be interesting to
investigate the effect of platelet concentrates in
such a situation, which is rather common when
performing tooth extraction. In a histomorphometric study in humans, Ahn and Shin reported that
after tooth extraction, sites previously affected by
advanced periodontal disease tend to regenerate
more slowly than disease-free sockets51. The latter
showed new bone formation exceeding 50% of
the total tissue after 8 weeks, while the diseased
sockets took about 16 weeks to achieve the same
outcome51. While a previous study has shown positive outcomes when using platelet concentrates for
post-extraction implants in infected sockets52, no
evidence is still available regarding infected socket
healing. Further comparative studies are needed
to understand if platelet concentrates are able to
accelerate the healing process in infected sockets.

Another factor that should be considered is the
method of preparation of the platelet concentrates.
In many included studies, the preparation methods
were not described in detail (see Table 3). Moreover,
such methods were rather heterogeneous, leading
to platelet-rich preparations with different characteristics and possible biological activities. For exam-

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342 ̈

Del Fabbro et al

Socket healing using platelet concentrates

ple, while PRGF contains a negligible amount of
leukocytes53, with the specific aim of reducing the
concentration of pro-inflammatory cytokines17,43,53,
other preparations like PRP or PRF contain a medium
to high concentration of these cells16,18. It still has
to be made clear if the presence of leukocytes may
represent a true benefit for the biological activity of
platelet concentrates.
It also has to be considered that only one study
was judged at low risk of bias44 while most of the
studies presented a medium43,45 or high46-48 risk of
bias due to flaws in the experimental design. This

aspect should be considered in further research in
order to standardise the study protocol, reducing the
risk of confounding factors and biases.
With regard to the association between platelet
concentrates and the use of graft materials for filling
the socket, the present review could not prove any
type of effect. In fact, only in one study, the postextraction sockets were filled with autogenous bone
in both groups43. This study found better hard and
soft tissue healing in the test group, in which PRGF
was mixed with autogenous bone. In another study
in the test group, MGCSH (medical-grade calcium
sulphate hemihydrate) was combined with PRP in
the test group47. These few reports did not allow
any conclusion to be drawn about the effect of platelet concentrates combined with autogenous bone
or bone substitutes, nor to make comparisons with
previous studies evaluating graft materials in socket
healing14,54.
The effect of the use of platelet-rich preparations on bone healing appeared to be heterogeneous. In some studies with histologic and histomorphometric evaluation, it seemed that PRP could
produce a wider and earlier organisation of bone
trabeculae and greater bone volume percentage
as compared to the control43,44,47. However, other
authors using different techniques had not found
any significant difference between control and test
groups48. Results from different types of radiographic analysis provided generally better outcomes
for the test groups although not always achieving
significance44-46. Other authors investigated the
role of platelet-derived growth factors in the bone
healing process55. Even though most growth factors are involved in different steps of bone healing,
representing signalling molecules that support the

Eur J Oral Implantol 2014;7(4):333–344

formation of a fibrin matrix, and promote proliferation of osteoblasts and osteoid formation, the
evidence for a relevant clinical effect is still poor. For
these reasons, the efficacy of platelet concentrate in
enhancing bone healing should not be considered
supported by sufficient literature as also stated in
a previous review55. On the contrary, a positive
effect on soft tissue healing has been observed in
most of the included studies, even though it was
not systematically assessed. Moreover, as found in
other comparative studies dealing with various surgical procedures56-59, a beneficial effect of platelet
concentrates on postoperative quality of life could
be evidenced, as a consequence of the enhanced
soft tissue healing42,44,45.
Finally, it was observed that the content of
platelet alpha granules might have a bactericidal
effect, mediated by molecules called thrombocidines60. This aspect was confirmed by recent in
vitro studies on the microbicidial effects of PRP on
various oral bacterial species61-63 as well as against
C albicans63. Such properties of the platelets could
represent an important tool in the fight against
postoperative infections that would deserve further
investigation.

̈ Conclusions
Based on the results of the present systematic review,
the following conclusions can be made:
t
A positive effect of platelet concentrates in accelerating bone healing is only suggested but could
not be clearly demonstrated by radiographic

assessment.
t
There is limited histological evidence of better
bone quality as well as histomorphometric evidence of greater bone formation in the first 3
months after tooth extraction, when using platelet concentrates.
t
There is suggestion (but not clear evidence) of
the beneficial effect of platelet concentrates on
soft tissue healing after tooth extraction.
t
There is limited evidence that the use of platelet
concentrates is associated with the reduction of
patients’ pain perception in the first postoperative week.


Del Fabbro et al

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