Article_6_2_4-1

MAXILLOFACIAL SURGERY
Original Articles EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUS-
ITIS: A PILOT STUDY
Daniela Miricescu1a, Alexandra Totan1b*, Ioana Ruxandra Rusu2c, Vitali Movradin3d, Mihaela Moisescu4e,
Constatin Ștefani5f, Iulia-Ioana Stănescu1g, Radu Rădulescu1h, Cosmin Totan6i, George Costin Rusu7j,
Maria Greabu1k
1.
Department of Biochemistry, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania
2.
Department of Anatomy and Embryology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania
3. Private Dental Practice, Bucharest
4.
Center for Excellence in Biophysics and Cellular Biotechnology Research, “Carol Davila” University of Medicine and Pharmacy
5.
Department of Family Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, “Carol Davila” University
Central Emergency Military Hospital, Bucharest, Romania
6.
Department of Oral Maxillofacial Surgery, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania
7.
Department of Modern Languages, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania

a
Chem, MSc, PhD, Lecturer
b
DMD, PhD, Associate Professor
c
DMD, PhD, Lecturer
d
DMD
e
DMD, PhD, Lecturer
f
DMD, PhD, Lecturer
g
DMD, PhD, Assistant Professor
h
DMD, PhD, Assistant Professor
i
DMD, PhD, Lecturer
j
DMD, PhD, Lecturer
k
DMD, PhD, Professor, Head

ABSTRACT DOI: https://doi.org/10.25241/stomaeduj.2019.6(2).art.4
OPEN ACCESS This is an Open Access
article under the CC BY-NC 4.0 license.
Introduction: Chronic odontogenic maxillary sinusitis (CMOS) is a frequent
inflammatory process pertaining to the oro-maxilo-facial pathology. Platelet-rich Peer-Reviewed Article

plasma (PRP) is a natural source of growth factors, which have the potential to Citation: Miricescu D, Totan A, Rusu IR,
Movradin V, Moisescu M, Ștefani C, Stănescu I I,
stimulate and accelerate the wound healing process. Rădulescu R, Totan C, Rusu GC, Greabu M, Effects of
The aim of this study is to observe the effects of the PRP growth factors in patients etching mode on bond strength of universal
adhesives. Stoma Edu J. 2019;6(2):118-123
with CMOS.
Received: June 11, 2019
Methodology: Inflammatory oral mucosa was collected from five patients Revised: June 21, 2019
diagnosed with CMOS, and it was incubated with 2 mL PRP for 7 days. PRP Accepted: June 26, 2019
Published: June 27, 2019
was obtained from venous blood collection from each patient. The control
*Corresponding author:
samples were represented by inflammatory sinus mucosa without adding PRP. Associate Professor Alexandra Totan, DMD, PhD
The following biomarkers were measured using cell lysate: insulin receptor (IR) Department of Biochemistry, Faculty of Dental
Medicine, “Carol Davila” University of Medicine a
and insulin-like growth factor 1 receptor (IGF-1R), glycogen synthase kinase 3 nd Pharmacy Bucharest, Bucharest, Romania
8, Blvd. Eroii Sanitari, Sector 5,
beta (GSK3β), glycogen synthase kinase 3 alfa (GSK3α) performed by Multiplex RO-050474 Bucharest, Romania
technology. Tel: +40721274932;
Fax: +400213110984;
Results: The results revealed statistically increased levels for all four parameters e-mail: alexandratotan99@gmail.com

in patients with CMOS versus controls (p < 0.05). Growth factors from PRP bind Copyright: © 2019
to receptors with tyrosine kinase activity, cellular event being correlated with the Editorial Council for the Stomatology Edu
Journal.
cell proliferation. The radiological control of patients 10 months after PRP
administration revealed a decrease in the thickness of the sinus lining up to 3
times.
Conclusions: The growth factors released from platelets should be regarded as a
positive effect source in the case of patients diagnosed with CMOS. These growth
factors should activate the oligopotente stem cells which will finally lead to sinus
mucosa regeneration. Future studies are needed to understand the molecular
mechanisms that occur at the sinus level.
Keywords: Inflammation; Platelet-rich plasma (PRP); Sinusitis; Chronic
odontogenic maxillary sinusitis (CMOS).

118 Stoma Edu J. 2019;6(2): 118-123 http://www.stomaeduj.com
EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY

Original Articles
1. Introduction erythrocytes and platelers. Sodium citrate was used
CMOS is an inflammation of the maxillary sinus as anticoagulant to prevent the initiation of the
caused by dental infection. Patients with chronic coagulation cascade. The samples were centrifuged
periodontitis have an increased risk of developing at 4000 rpm for 5 minutes. Using the trepanation
maxillary sinusitis caused by intra-antral foreign technique, inflammatory sinus mucosa was collected
bodies or by oroantral fistulas after tooth extraction from the maxillary sinus in sterile tubes and was
[1,2]. According to the literature in the field, the incubated with PRP for 7 days. PRP was injected in the
incidence of this disease in the adult population inflammatory maxillary sinus PRP was injected in all
is 10-12%, but according to the latest studies, the patients based on a clinical chart.
incidence increased to 41% [3-5]. So far, there is Along with the clinical study, lab study was conducted
no gold standard in choosing the most suitable in order to underline the PRP procedure on the
treatment method for this inflammatory process. mucus, to prove the effect of growth factors implied
Until now, specialized literature suggests 3 main in the local healing process. The control samples were
clinical methods to treat CMOS: the Caldwell-Luc represented by the inflammatory mucosa that were
operation, functional endoscopic sinus surgery not treated with PRP and were collected in sterile
and finally dental extraction or dental treatment. tubes containing phosphate-buffered aline solution
Using these surgical methods presents several (pH 7.2). The samples were sonicated on ice (10 min,
disadvantages: bleeding, infraorbital nerve damage, Sonoplus HD 2070, BANDELIN electronic GmbH &
facial swelling, pain, and significant hemorrhage may Co. KG, Berlin, Germany) and the lysate was stored at
appear. These treatment methods require patient -80°C. All patients signed an informed consent and
hospitalization and general anesthesia with possible agreed to participate in the study. Insulin receptor (IR),
complications [6,7]. Platelet-rich-plasma (PRP) is a insulin-like growth factor 1 receptor (IGF-1R) glycogen
natural source of growth factors being considered an synthase kinase 3 beta (GSK3β) and glycogen synthase
endogenous therapeutic technology used in many kinase 3 alfa (GSK3α) were detected using Luminex
medical fields. PRP has the potential to stimulate and technology and Magnetic Bead-Based Multiplex assays
accelerate the healing process [8,9,14]. The main aim (Akt/mTOR, Total protein 11-plex Magnetic Bead kit, 96
of this pilot study was to observe the effects of PRP- well plate, 48-612 MAG). This method can detect all the
related growth factors in patients diagnosed with mentioned biomarkers from the same sample.
CMOS. 2.1. Statistical analysis
The statistical analysis was performed using student
2. Materials and Methods t-test and p-value less then 0.05 was considered
The pilot study included five patients (4 men and 1 statistically significant.
woman aged 40-64) diagnosed with CMOS following
a dental exam and computer tomography (CT) 3. Results
(Fig.1). PRP was obtained by venous blood collection The results of our study reveled statistically increased
in tubes containing separating gel with an inert levels of IR, IGF-1, GSK3β and GSK3α for mucosa
polymer necessary to ensure the separation between samples treated with PRP compared with mucosa

a b
Figure 1. Computer tomography from a patient included in the study:
a. Coronal CT dental scan showing. Opacified right maxillary sinus - before PRP treatment;
b. Opacity of right maxillary sinus reduced after PRP intrasinusal infiltration (Used with permission of pacient) - after PRP treatment

Stomatology Edu Journal 119
EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY

Original Articles Table 1. Mean values for all four parameters detected.

Parameters (MFI) Patients Controls p

IGF-1R 142.33 ± 16.7 63.37 ± 16.7 < 0.05

IR 204.5 ± 8.23 78.97 ± 8.23 < 0.05

GSK3β 70.625 ± 20.44 30 ± 20.44 < 0.05

GSK3α 111.75 ± 43.12 40.375 ± 43.12 < 0.05

Figure 2. Graphic represenation of all 4 studied parameters versus their controls

samples that did not received PRP. Our results are of IGF-1. The positive effects of PDGF were seen
presented in Table 1 and Fig. 2. in the treatment of the ulcerous foot in diabetic
patients [17,18]. Platelets, macrophages, fibroblasts
4. Discussions and mesenchimal stem cells secrete EGF, which is
PRP is currently used in many medical fields such released at a high concentration at the beginning of
as orthopedic, pediatric, maxillofacial and plastic the healing process. EGF plays important roles in the
surgery, sport medicine, and cosmetic and dental proliferation, differentiation, growth and migration
implant surgery [9-13]. FDA (Food and Drug of keratinocytes and epithelial cells [14,15].
Administration) has classified PRP as a minimally IGF is secreted by fibroblasts and is involved mainly
manipulated tissue and an autologous blood product in the inflammatory and proliferative phase II, 58,
with multiple benefits for patients [14]. Growth 72. Decreased IGF concentrations were observed
factors play key roles in the complex process of tissue in diabetic patients with chronic wounds. Clinical
healing and regeneration, being signaling proteins trials conducted on laboratory animals such as
that influence the metabolism of other cells [15,16]. diabetic and healthy rats, or rabbits showed that the
Transforming growth factor (TGF-β), platelet-derived exogenous IGF application accelerates the healing
growth factor (PDGF), vascular endothelial growth process [16-18]. In combination with other growth
factor (VEGF), insulin-like growth factor-1 (IGF-1) and factors such as PDGF and EGF, IGF exhibits much more
epidermal growth factor (EGF) are present in PRP powerful biological effects promoting keratinocyte
[10-16]. PDGF is secreted by platelets, macrophages, migration and enhancing tissue repair [19-21]. VEGF
keratinocytes, endothelial and muscle cells. PDGF is secreted by plateles, keratinocytes, macrophages
is one of the growth factors that are secreted when and fibroblasts and manifests strong paracrine
an injury occurs, stimulating many metabolic effects on endothelial cells, promotes and supports
processes such as protein and collagen synthesis. the process of wound angiogenesis. It is the main
It also promotes the proliferation and migration growth factor that initiates the angiogenesis process
of endothelial cells, exerting angiogenic effects, in granulation tissue [21,22]. VEGF growth factors
stimulates the production of TGF-β that initiates are implicated in the physiological and pathological
collagen synthesis and stimulates the production processes of vasculogenesis, angiogenesis, vascular

120 Stoma Edu J. 2019;6(2): 118-123 http://www.stomaeduj.com
EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY

Original Articles
permeability and lymhangiogenesis [22,23]. in protein translation and cell growth. The results of
Clinical and experimental studies conducted on the biochemical evaluations are correlated with the
diabetic mice and dogs, as well as diabetic patients findings of CT performed at 10 months after the PRP
reported very good results by applying VEGF, which injection, according to Fig. 1.
accelerate healing by increasing epithelialization,
angiogenesis and granulation tissue formation [24- 5. Conclusions
27]. Many cell types secrete TGFβ such as platelets, In conclusion, the growth factors released from
T lymphocytes, macrophages, keratinocytes, platelets should be regarded as a positive effect
fibroblasts, muscle and endothelial cells. TGFβ source in the case of patients diagnosed with
induces synthesis of collagen and fibronectin due CMOS. These growth factors should activate the
to chemotactic effects on macrophages and inhibits oligopotent stem cells which will finally lead to sinus
the activity of metalloproteases [25]. IGF-1R, IR, mucosa regeneration. Future studies are needed to
GSK3α, GSK 3β, detected in our pilot study are part understand the molecular mechanisms that occur at
of the signaling cascade called Akt/mTOR or protein the sinus level.
kinase B. This signaling pathway plays a central role in
numerous cellular processes such as cell proliferation Author Contributions
regulation, survival and glucose metabolism. Akt is All authors equally contributed to the present
activated by insulin, which presents the receptor with manuscript. DM: participated in sample analysis
tyrosine kinase activity [28]. By binding the insulin and manuscript writing; AT: participated in sample
to the extracellular domain of the receptor there analysis and manuscript writing, IRR: participated
occurs the autophosphorylation of the receptor in study design, data collection; VM: participated in
that is recognized by the IRS (insulin receptor the study design and sample collection, being the
substrate), and further there is a series of cascade OMF surgeon to produce the clinical samples; MM:
phosphorylates with Akt activation that will lead to participated in sample analysis, CS: participated
cell growth and proliferation. Akt may be activated in manuscript writing; IIS: manuscript writing; RR:
by many growth factors such as those found in PRP manuscript writing; CT: participated in manuscript
or cytokines [28]. The results of the current study writing; GCR: translation of the text, proposing and
reflect statistically significant increased levels for IGF- managing the whole work; MG: participated in
1R, IR, GSK3α, GSK3β in the case of PRP-treated oral critical review of the manuscript.
mucosa versus oral mucosa without PRP treatment.
Growth factors from PRP bind to receptors with Acknowledgments
tyrosine kinase activity, such as the insulin receptor, This work was proposed and managed by The
actives Akt signaling pathway, promotes increase Hospitallers Knights’ Club – Knights of Malta.

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Daniela MIRICESCU
Chem, MSc, PhD, Lecturer
Department of Biochemistry
Faculty of Dental Medicine
„Carol Davila” University of Medicine and Pharmacy Bucharest
Bucharest, Romania

CV
Daniela Miricescu graduated from the Faculty of Chemistry (Biochemistry Department) in 2006, in 2008 she obtained
her Master’s of Biochemistry and Molecular Biology (Biology Faculty) and in 2012 she obtained her PhD from the „Carol
Davila” University of Medicine and Pharmacy Bucharest, Romania.
Since 2016 she has been a lecturer at Department of Biochemistry, Faculty of Dental Medicine, „Carol Davila” University
of Medicine and Pharmacy Bucharest.
Her research field includes salivary studies on oxidative stress in various oral pathologies, the effects of obesity on
laboratory animals, the effects of PLGA nanoparticles both in vivo and in vitro, the effects of plasma-rich plasma in
patients diagnosed with chronic maxillary sinusitis, and the study of Akt (protein kinase B) signaling pathways in health
and disease .

122 Stoma Edu J. 2019;6(2): 118-123 http://www.stomaeduj.com
EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY

Original Articles
Questions
1. PRP is:
qa. Natural source of growth factors
qb. Natural source of proinflammatory agents
qc. Natural source of antiinflammatory agents
qd. Natural source of stem cells

2. PRP may be used in:
qa. Ortopedic surgery
qb. Dental implant surgery
qc. Plastic surgery
qd. Cosmetic

3. IGF:
qa. Is secreted by fibroblasts
qb. Is involved in proliferative phase
qc. Promotes keratinocytes migration
qd. Promotes tissue repair

4. Akt (protein kinase B) is implicated in:
qa. Cell proliferation
qb. Glucose metabolism
qc. Celular survival
qd. Necrosis

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