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Review Article

The Hemostatic Properties of Chitosan in Oral Surgery

Rocco Franco1, Francesco Gianfreda2, Michele Miranda2, Alberta Barlattani3, Patrizio Bollero2
Departments of Biomedicine and Prevention, 2Systems Medicine and 3Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy
1

Abstract
Chitosan (CS) belongs to the natural linear aminopolysaccharide family. It is formed by a repetition of D‑glucosamine units (deacetylated
units) and a smaller number of N‑acetyl‑D‑glucosamine units. Their distribution is casual. It derives from chitin which is a naturally occurring
polysaccharide in the arthropod exoskeleton. CS is a biocompatible material and for this reason it is used in medicine, especially in dentistry.
It also has anti‑inflammatory and regenerative properties. It is used in conservative dentistry, periodontology, especially in oral surgery. Its
antibacterial and hemostatic properties are useful in the surgical treatment of patients on anticoagulant/antiplatelet therapy. The purpose of
this work is to analyze through a systematic review of the literature on the use of CS as a local hemostatic.

Keywords: Chitosan, hemostasis, oral surgery

Introduction for the prevention of caries. Its use is also in endodontics for
its strong antibacterial qualities. In fact, it acts against the most
Chitosan (CS) belongs to the natural linear aminopolysaccharide
resistant bacterial species in the root canals. CS interacts with
family. It is formed by a repetition of D‑glucosamine
the negative charges of bacterial cells and causes the loss of
units (deacetylated units) and a smaller number of
intracellular components.[2] Its use is also in periodontology. It
N‑acetyl‑D‑glucosamine units. Their distribution is casual.
works by preventing the loss of periodontal tissues and helping
It derives from chitin, which is a naturally occurring
their regeneration. Many scientists agree on the possible use
polysaccharide in the arthropod exoskeleton. CS is produced
of CS to regenerate the lost periodontal tissues. Furthermore,
from chitine through an N‑deacetylation process, which leads
given its regenerative properties, it forms scaffolds on which
to the breaking of the bonds and the removal of the acetyl
osteoblasts produce bone matrix.[3] In conclusion, CS can be
group. However, this deacetylation never occurs completely on
used in various branches of dentistry. Its multiple properties
the whole chitin chain. Bacterial and fungal enzymes are used
make it an excellent material. However, we focus attention
to perform deacetylation. CS has several beneficial properties
on the use of CS as a local hemostatic agent in patients with
for humans.[1] Among the various biological activities are
clotting problems.[4]
listed: hemostatic effects, promotion of wound healing,
increases the activity of the immune system, antibacterial CS is used to promote wound healing as a local hemostatic or
activity, and promotes bone formation. CS finds various bone regeneration agent. The purpose of this work is to carry
applications in medicine; it also has a marked biocompatibility out a systematic review of the use of CS as a local hemostatic
with human tissues. Specifically, in humans, they have the agent. Indeed, the further aim of the study is to evaluate the
ability to attract macrophages and neutrophils and can stimulate
fibroblasts to produce type IV collagen. It also stimulates
Address for correspondence: Dr. Rocco Franco,
leukocytes to produce cytokines and angiogenetic factors. It Department of Biomedicine and Prevention, University of Rome “Tor
has a chemical similarity to cellulose and is not degradable Vergata”, Via Montpellier, 100133 Rome, Italy. University Hospital of Rome
by the human body. It is a polysaccharide of natural origin, “Tor Vergata”, Dental Clinic, Viale Oxford, 81, Rome, Italy. 
nontoxic, highly biocompatible, and biodegradable and has E‑mail: rocco.franco@ptvonline.it
strong antibacterial properties. It also has the ability to form
a film and gel, which is very useful in conservative dentistry
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How to cite this article: Franco R, Gianfreda F, Miranda M, Barlattani A,
Bollero P. The hemostatic properties of chitosan in oral surgery. Biomed
DOI:
10.4103/bbrj.bbrj_43_20
Biotechnol Res J 2020;4:186-8.
Submitted: 21-Mar-2020; Accepted: 07-Apr-2020; Published: 12-Sep-2020

186 © 2020 Biomedical and Biotechnology Research Journal (BBRJ) | Published by Wolters Kluwer ‑ Medknow
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Franco, et al.: Hemostasis and chitosan
application of this material in the postextraction cavities of
patients on antiplatelet or anticoagulant therapy.
Materials and Methods
The study was conducted utilizing the main scientific
databases (PUBMED, MEDLINE, and WEB of SCIENCE).
The time window considered for the electronic search was from
March 1, 2007, to March 1, 2020. The term “melatonin” was first
combined with “periodontal disease” and then independently
with “salivary concentration” using the connector “AND.”
The web search was assisted using Medical Subject Headings.
The criteria for this review are described in the PRISMA
flow diagram. The purpose of this review is to answer to the
following questions using a PICO method (P: patient problem/
population; I: intervention; C: comparison; and O: outcome):
(1) Can CS help as a hemostatic in oral surgery, especially in
patients on anticoagulant/antiplatelet therapy?
The following inclusion criterion was used: articles in English,
human studies, and clinical trials. Two independent people
search with the same keywords all articles and select the
article founding. The risk of bias in this phase is solved by an
independent author that conducts the same search. The phase
of the screening is carried out by the two independent research
that excluded the article duplicated, review, and animal study.
The articles found in this phase are 30. Ten articles are excluded
because they are duplicates and they do not respect the topic
proposed in this review.
The phase of eligibility is conducted by other two reviewers.
These authors compare the article founding and select the
article that asked the PICO. Articles which did not contain data
regarding CS, oral surgery, and hemostatic agents are excluded
from the study. The authors read first the abstract of all articles
excluded, which did not respect the inclusion criteria, after
reading the complete test of the remaining articles. In this
phase, 15 articles are excluded.
In this phase, the risk of bias is solved by an independent
author, completely external, and unknown to the authors. The
number of articles remaining in this phase is five. One article
is excluded because they did not use the periodontal index and
treats only of oral health.
The synthesis of data is carried out by the authors. All data
were extracted. The author reads first the abstract of all articles
after reading the complete test of the articles. All the reviewers
extract the data regarding the CS, time of bleeding. Articles
which do not contain the data and the previous keywords were
excluded. All doubts, regarding the included articles, are solved
by contacting the author [Table 1].
Results
Two independent scientists searched the previously mentioned
keywords, read the titles, and summarized the abstracts of
articles. During an initial reading, they excluded the articles
that did not respect the topic. Therefore, articles that responded
Biomedical and Biotechnology Research Journal ¦ Volume 4 ¦ Issue 3 ¦ July-September 2020
Table 1: Flow chart of the review process
Identification Articles identified through principal database
of articles (PubMed, Medline, and Web of Science) (n=30)
Screening time After an initial read of titles and abstract
n excluded: 10
Eligibility A full-text reading and a check of inclusion or
exclusion criteria
n excluded: 15
Included Studies included
n: 3
to the key characteristics were selected. These remaining
articles were read, and one of them was excluded because
it did not conform to the inclusion criteria established. The
complete text of the three remaining articles was read, and
all were found to respect the inclusion criteria. In conclusion,
three articles were included in the present review. The scientists
extrapolated the following data: bleeding time, number of
patients, mean age, sex, and type of drugs. Data, regarding
the bleeding time in patients with CS, were taken into account
and extrapolated. The study of Sarkar compares the effects
of PRP and CS on the healing of the sockets in patients with
antiplatelet therapy. It also assessed the hemostatic effects of
the two materials. Sixty patients on oral antiplatelet therapy
who required dental extractions were enrolled. The patients
were divided into two groups: the first group of 30 patients was
treated with platelet‑rich fibrin (PRF), and the second group
of 30 patients were treated with CS hydrogel. Bleeding time
was assessed for each of the two groups. Furthermore, the
following parameters were detected in the 1st‑, 3rd‑, and 7th‑day
postextraction: secondary pain/bleeding/scarring/soft‑tissue
dehiscence/alveolar osteitis. Bleeding time was shorter in the
CS group (2.64 min) than in the PRF group (1.182 min) with a
P < 0.001. Postoperative pain was less in the PRF group (3.2,
1.4, and 0.37 on 1st, 3rd, and 7th day, respectively) than in
the study group (3.4, 1.67, and 0.53 on 1st, 3rd, and 7th day,
respectively) with a P = 0.001.[5]
The study of Kumar found the effects of CS on hemostasis
in patients with oral anticoagulant therapy. Thirty patients
between 18 and 90 years were enrolled. Seafood allergy
patients were excluded. The study was structured as a split
mouth. Patients on oral anticoagulant therapy with international
normalized ratio (INR) <4 were also enrolled. Therapy was not
altered during surgery. The collected data were subjected to
statistical analysis using unpaired t‑tests. The sites treated with
CS coagulated in 1.49 min, while the control sites coagulated
in 4.06 min (P < 0.001). As for pain, the treated sites showed
a reduction (1.87 and 1.27, respectively, on the 1st and 3rd day)
compared to the control sites (4.0 and 1.87, respectively, on
the 1st and 3rd day) P value (0.001 and 0.001, respectively). In
addition, the sites treated with CS had better healing both on
the 1st and 3rd postoperative day (P < 0.0001).[6]
The study of Efeoğlu evaluates the effects of CS and surgicel,
a topical hemostatic, in patients with cirrhosis. Fifty patients
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Franco, et al.: Hemostasis and chitosan
with cirrhosis were enrolled. A randomized, double‑blind study
was performed. Patients were divided according to the type of
cirrhosis. The bleeding time, the trauma score, and the correct
bleeding time (during postoperative reviews) were calculated in
the two groups. The patients were contacted by phone after 5 h,
10 h, and for another 5 days twice a day, and a telephone test was
performed to evaluate bleeding or any complications. The two
groups underwent an equal number of extractions (40 teeth each).
No statistically significant differences were observed, especially
regarding bleeding time, as well as for the other parameters.[7]
Conclusion
CS is a natural linear aminopolysaccharide. Its structure is
based on repetitive units of D‑glucosamine (deacetylated
units) and less randomly distributed N‑acetyl‑D‑glucosamine
units (acetylated units), connected by Β‑(1–4) bond. It
forms the crystalline microfibers of arthropod and cell wall
exoskeletons. CS derives from the N‑deacetylation of chitin.
CS has anti‑inflammatory properties and high biocompatibility.
CS has numerous applications in the medical field.[8] In fact,
among its main properties are regenerative ones. CS stimulates
the activity of macrophages, fibroblasts to produce collagen
VI, and stimulates cells to produce growth factors useful for
regeneration. For this, the CS promotes the healing of wounds
or traumatic events. Furthermore, thanks to its conformation,
it is used as a scaffold for bone formation. CS is widely used in
oral surgery because of its regenerative abilities.[9] Specifically,
it inhibits bleeding, promotes the formation of granulation
tissue, and promotes a scaffold for bone regeneration. In fact,
in this review, we have analyzed the hemostatic properties of
CS. We evaluated the hemostatic properties of CS in patients
on anticoagulant or antiplatelet therapy.[10] The increase in heart
and cardiovascular diseases caused an increase in the use of
these drugs. Therefore, in dentistry, it is useful to know how
to manage this category of patients. The current guidelines
for antiplatelet drugs do not suspend them, as they would
cause an increased thromboembolic risk. Obviously, in the
case of extractions up to three dental elements,[11] as for oral
anticoagulants, the current guidelines provide not to stop the
oral anticoagulant drug if we are faced with an INR of <3.5.[12]
Therefore, the discovery of new hemostatic materials, including
CS, becomes particularly useful. The purpose of this review
was the analysis of the hemostatic properties of CS in groups
of patients receiving anticoagulant and antiplatelet therapy. In
addition, regenerative and healing properties were evaluated.
Although there are few studies in the literature.[13‑15] All the
studies affirm the hemostatic and regenerative properties of
CS. All the studies structured the studies either split mouth or
randomized clinical trial, in which only sutures were applied in
the control group.[5‑7] Only one study evaluated the efficacy of
CS in comparison with another local hemostatic widely used;
in fact, in this case, the results showed an equal hemostatic
efficacy. In the remaining studies, however, both primary and
secondary hemostatic capacity was statistically significant.
188 Biomedical and Biotechnology Research Journal ¦ Volume 4 ¦ Issue 3 ¦ July-September 2020
Hence, we can conclude that CS can be used in oral surgery in
complete safety and efficacy, especially in those categories of
patients on anticoagulant/antiplatelet therapy. In fact, the use
of this material can prevent the patient from stopping the drug
and subjecting it to thromboembolic risk. Numerous clinical
trials will be needed to confirm the effectiveness of this material.
Acknowledgment
I thank Prof. Tiberti for the help in the data collection.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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