湖南大学学报（自然科学版） 第 51 卷 第 3 期

Journal of Hunan University (Natural Sciences） 2024 年3月

Vol. 51 No. 3
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March 2024

Open Access Article https://doi.org/10.55463/issn.1674-2974.51.3.12

Effect of Black Crab (Scylla Serrata) Chitosan Gel on the Three-Dimensional

Socket Response and Fibroblasts after Tooth Extraction in Rattus Norvegicus
Hendry Rusdy*, Gostry Aldica Dohude, Bagoes Anggoro Cesar Putro, Nasywa Tiara Syadana,
Samuel Kevin
Department of Oral and Maxillofacial Surgery, University of North Sumatera, Medan, Indonesia
* Corresponding author: hеndry.rusdy@usu.аc.id

Received: December 7, 2023 / Revised: January 2, 2024 / Accepted: February 10, 2024 / Published: March 29, 2024

Abstract: Tooth extraction is a common procedure in dentistry that can result in wounds to the soft and
hard tissues of the alveolar process, thereby triggering the healing process. The wound healing process is often
complicated by several factors, leading to delayed wound healing. The principles of wound healing involve four
phases: hemostasis, inflammation, proliferation, and remodeling. This study aimed to determine the effect of black
crab (Scylla serrata) chitosan gel on three-dimensional socket response and fibroblast proliferation after tooth
extraction in Wistar rats (Rattus norvegicus). In this study, chitosan material with a degree of deacetylation of
84.9% was used, thus exhibiting good biological properties in the wound healing process. This research is an
experimental study with a post-test only with a controlled group design. The sampling technique used was
purposive sampling, and the sample size was calculated using the Federer formula. Observations were made by
measuring the mesial-distal, lingual-buccal, and socket depths using calipers and the UNC15 probe and observing
the number of fibroblasts histologically on Days 1, 3, and 7. The results of the one-way ANOVA and post hoc LSD
tests indicate significant outcomes in socket wound closure and fibroblast proliferation in the chitosan gel group.
This study demonstrates that black crab (Scylla serrata) chitosan gel is effective in accelerating socket wound
closure and stimulating fibroblasts in socket wounds after tooth extraction.
Keywords: tooth extraction, black crab chitosan gel, socket response, fibroblast.

锯缘青蟹壳聚糖凝胶对褐家鼠拔牙后三维窝反应及成纤维细胞的影响

摘要：拔牙是牙科中的常见手术，可能会导致牙槽突的软组织和硬组织受伤，从而引发
愈合过程。伤口愈合过程往往因多种因素而变得复杂，导致伤口愈合延迟。伤口愈合的原理
涉及四个阶段：止血、炎症、增殖和重塑。本研究旨在确定黑蟹（锯缘青蟹）壳聚糖凝胶对
维斯塔大鼠（褐家鼠）拔牙后三维窝反应和成纤维细胞增殖的影响。本研究使用脱乙酰度为 8
4.9%的壳聚糖材料，因此在伤口愈合过程中表现出良好的生物学特性。本研究是一项实验研
究，仅进行受控组设计的后测。所采用的抽样技术是有目的抽样，样本量使用费德勒公式计
算。通过使用卡尺和北卡罗来纳大学 15 探针测量近中-远中、舌-颊和牙槽深度并在第
1、3 和 7 天观察成纤维细胞的组织学数量来进行观察。单向方差分析和事后分析的结果迷幻
剂测试表明壳聚糖凝胶组在牙槽窝伤口闭合和成纤维细胞增殖方面具有显着效果。这项研究

© 2024 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons
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 Rusdy et al. Effect of Black Crab (Scylla Serrata) Chitosan Gel on the Three-Dimensional Socket Response and Fibroblasts after Tooth
Extraction in Rattus Norvegicus, Vol. 51 No. 3 March 2024
104
表明，黑蟹（锯缘青蟹）壳聚糖凝胶可有效加速牙槽窝伤口闭合并刺激拔牙后牙槽窝伤口中
的成纤维细胞。
关键词：拔牙，黑蟹壳聚糖凝胶，牙槽反应，成纤维细胞。

1. Introduction dimensional socket response and the number of

Tooth extraction is a common procedure in fibroblasts.
dentistry. The extraction results in wounds in soft and
hard tissues of the alveolar process, causing injury. 2. Materials and Methods
Often, this procedure can lead to complications that This research was conducted in the Pharmacology
slow down the healing process [1]. The impacts of and Therapeutics Laboratory at the Faculty of
these complications may include pain, unpleasant odor, Medicine, the Analytical Chemistry Laboratory at the
exudate discharge, and decreased patient productivity. Faculty of Mathematics and Natural Sciences,
Various factors contribute to delayed wound healing, University of North Sumatera, and the Prospective
including age, poor oral hygiene, smoking, and the size Pathological Anatomy Laboratory. The population of
of the post-extraction wound [2]. this study consisted of Wistar rats, and the sample size
The wound healing process involves the was calculated using the Federer formula. The required
replacement of damaged or lost tissue with new tissue number of samples was 30 Wistar rats. The samples
to restore function. The principles of wound healing were divided into six groups: (1) placebo gel CMC-Na
encompass four phases: hemostasis, inflammation, on Day 1, (2) placebo gel CMC-Na on Day 3, (3)
proliferation, and remodeling. The initial response to placebo gel CMC-Na on Day 7, (4) 3% chitosan gel on
the wound or damage begins with hemostasis, followed Day 1, (5) 3% chitosan gel on Day 3, and (6) 3%
by tissue healing characterized by the replacement of chitosan gel on Day 7. Each group consisted of five
cells with fibrous tissue. Fibroblast cells play a crucial samples.
role in the healing process. During the proliferation
phase, these cells move to the wound area, multiply,
and produce collagen matrix to repair the damaged
tissue [3]. Optimal wound healing management has led
to advancements in the understanding of wounds,
healing, and their treatment. The use of natural
substances for wound healing has gained acceptance
due to the minimal side effects.
In Indonesia, solid waste, such as crab shells,
amounts to approximately 1000 tons per year. This
waste has been proven to contain chitin, which can be Fig. 1 Flowchart of the research methodology (The authors)
processed into chitosan [4]. Chitosan is a linear random
copolymer of N-acetyl-D-glucosamine and 2.1. Chitosan Gel Preparation
deacetylated D-glucosamine linked by β-1,4 glycosidic The preparation of 3% chitosan gel was achieved by
bonds [5]. Chitosan is safe for use in healthcare, dissolving 3 g of chitosan powder in 100 ml of 1%
serving purposes such as wound healing, tissue acetic acid with a pH of approximately 4, following
regeneration, hemostatic material, wound dressing, and factory regulations. Once the chitosan is dissolved,
even capsule coatings [6]. Studies have shown that stirring is conducted with a stirrer while adding NaOH
chitosan gel is an effective wound healing preparation to adjust the pH to a neutral range. Subsequently, 3%
because of its good hemostatic, biocompatible, and chitosan gel is transferred into 100-ml bottles.
biodegradable properties, with no significant side
effects [7]. Majid Ali [8] revealed that chitosan from
black crab (Scylla serrata) shells has higher affinity
and deacetylation degree (up to 87%) than other crab
types, making it biologically superior.
Based on the above description, it is evident that
there has been significant research on the use of
chitosan in aiding wound healing. Therefore, the
researchers investigated the effectiveness of using
black crab (Scylla serrata) chitosan gel in healing after
tooth extraction, considering the clinical three- Fig. 2 Preparation of the chitosan gel (The authors)
 105

2.2. Extraction of Rat Teeth 2.5. Experimental Animal Surgery and Tissue
Before the experiment, the rats were acclimatized Retrieval
for 7 days. Subsequently, body weight measurements The rats were euthanized by anesthetizing them
were conducted before the rats received treatment. using ketamine via an intraperitoneal technique. After
General anesthesia in the form of ketamine injection the rats are deceased, excision is performed on the jaw
was administered at a dose adjusted to the weight of the tissues, which are then fixed with a Buffered Neutral
experimental animals. Tooth extraction was performed Formalin (BFN) 10% solution and placed in a
by restraining the lower part of the rat, followed by an specialized storage container.
incision on the left lower incisor region using a scalpel
and no. 15 blade. A curved artery clamp was placed on
the tooth to be extracted, followed by gently rocking
the tooth laterally until it was dislodged.

Fig. 6 Euthanasia and collection of rat jaw tissues (The authors)

2.6. Preparation of Histological Slides and

Fig. 3 Extraction of the experimental animal teeth (The authors)
Fibroblast Cell Count Observation
The extracted tissues were further decalcified by
2.3. Application of the Chitosan Gel
immersion in 10% EDTA solution. The fibroblast cell
Chitosan gel is applied to the socket using a 1 cc
count in tissue preparations was assessed using a
syringe twice a day for 7 days. The use of chitosan gel
binocular microscope at 400x magnification, with an
in both the control and treatment groups begins
ocular graticule placed within the lens, divided into
immediately after the injury. Group I employs placebo
five fields to avoid repeated counting.
gel, specifically CMC-Na, as a negative control,
whereas Group II uses chitosan gel with a
concentration of 3%, administered in a volume of 0.1
ml.

Fig. 7 Tissue preparation and histology of the fibroblasts (The

authors)

3. Results
Data processing and analysis were performed using
Fig. 4 Application of 3% chitosan gel (The authors) SPSS. The Shapiro-Wilk test was employed to assess
the normality of the data. Subsequently, a one-way
2.4. Clinical Observation of the Socket Response in ANOVA test was performed to determine the
Three Dimensions effectiveness of chitosan gel from black crab shell
Clinical observation of the three-dimensional socket (Scylla serrata) in tooth socket healing in vivo. This
response in the experimental animals was conducted on was followed by a post hoc LSD test to examine the
Days 1, 3, and 7 after tooth extraction. The observation comparisons between the three observation days.
involved assessing changes in mesial-distal width,
lingual-buccal width, and socket depth. These 3.1. Three-Dimensional Socket Closure Response
observations were measured using calipers. after Tooth Extraction
The assessment of wound healing speed after tooth
extraction in male Wistar rats was clinically evaluated
using the residual socket volume (RSV) calculation
method. In the control group, the average and standard
deviation of the RSV for Wistar rat socket wounds
treated with placebo gel (CMC-Na) on Days 1, 3, and 7
were 0.66 ± 0.11, 0.59 ± 0.11, and 0.48 ± 0.10,
Fig. 5 Measurement of the socket response (The authors) respectively. Meanwhile, in the treatment group, the
 Rusdy et al. Effect of Black Crab (Scylla Serrata) Chitosan Gel on the Three-Dimensional Socket Response and Fibroblasts after Tooth
Extraction in Rattus Norvegicus, Vol. 51 No. 3 March 2024
106
average and standard deviation of the RSV for Wistar days 1, 3, and 7 were 38.85 ± 4.90, 47.30 ± 1.20, and
rat socket wounds in the treatment group after applying 75.50 ± 7.78, respectively. Meanwhile, in the treatment
3% chitosan gel from the black crab shell (Scylla group, the average and standard deviation of the
serrata) on Days 1, 3, and 7 were 0.51 ± 0.73, 0.44 ± number of fibroblasts from the sockets of Wistar rats in
0.07, and 0.26 ± 0.04, respectively. the treatment group after applying 3% chitosan gel
from the black crab shell (Scylla serrata) on Days 1, 3,
Table 1 One-way ANOVA test for the socket response (The authors) and 7 were 24.05 ± 0.91, 94.70 ± 24.40, and 129.85 ±
Group DaySample Mean±SD P-Value
CMC-Na Day 1 4 0.66±0.11 0.000
25.30.
Day 3 4 0.59±0.11
Day 7 4 0.48±0.10 Table 3 One-Way ANOVA test of fibroblast cell proliferation (The
3% Chitosan Gel Day 1 4 0.51±0.73 0.000 authors)
Day 3 4 0.44±0.07 Group DaySample Mean±SD P-Value
Day 4 0.26±0.04 CMC-Na Day 1 4 38.85±4.90 0.000
Day 3 4 47.30±1.20
Day 7 4 75.50±7.78
Based on the results of the one-way ANOVA test, 3% Chitosan Gel Day 1 4 24.05±0.91 0.000
there was a significant difference in the 3% chitosan Day 3 4 94.70±24.40
gel treatment group between observations on Days 1, 3, Day 4 129.85±25.30
and 7, with a significance value of p=0.001 (p<0.05).
Meanwhile, in the control group with a placebo of Based on the results of the one-way ANOVA test,
CMC-Na, there was no significant difference between there was a significant difference in fibroblast cell
observations on Days 1, 3, and 7, with a significance proliferation across all data groups between the 3%
value of p=0.121 (p>0.05). According to the results of chitosan gel treatment group and the CMC-Na placebo
the post hoc LSD test, in the CMC-Na group, there was control group on observations on Days 1, 3, and 7, with
a significant difference between observations on Days a significance value of p=0.000 (p<0.05). According to
1 and 7 (p=0.048, p<0.05), but no significant difference the pos hoc LSD test, in the CMC-Na group, there was
was observed between observations on Days 1 and 3 a significant difference in the number of fibroblasts
(p=0.441, p>0.05) and between Days 3 and 7 (p=0.172, between observations on Days 1 and 7 and on Days 3
p>0.05). In the 3% chitosan gel group, there was a and 7, with a significance value of p=0.000 (p<0.05).
significant difference between observations on Days 1 However, there was no significant difference between
and 7 (p=0.000, p<0.05) and between Days 3 and 7 observations on Days 1 and 3, with a significance value
(p=0.004, p<0.05). However, no significant difference of p=0.053 (p>0.05). Meanwhile, in the 3% chitosan
was observed between observations on Days 1 and 3 gel group, there was a significant difference between
(p=0.158, p>0.05). observations on Days 1 and 3 with a p-value of 0.001
(p<0.05), between Days 1 and 7 with a p-value of
Table 2 Post hoc LSD test of the socket response (The authors) 0.000 (p<0.05), and between Days 3 and 7 with a p-
Group Day P-Value value of 0.037 (p<0.05).
CMC-Na Day 1 Day 3 0.441
Day 7 0.048*
Day 3 Day 7 0.172 Table 4 Post hoc LSD for fibroblast cell proliferation (The authors)
Group Day P-Value
3% Chitosan Gel Day 1 Day 3 0.158
CMC-Na Day 1 Day 3 0.053
Day 7 0.000*
Day 7 0.000*
Day 3 Day 7 0.004*
Day 3 Day 7 0.000*
Chitosan Gel 3% Day 1 Day 3 0.001*
Day 7 0.000*
Day 3 Day 7 0.037*

Fig. 8 RSVs on Days 1, 3, and 7 (The authors)

3.2. Number of Fibroblasts in Healing Socket

Wounds after Tooth Extraction Fig. 9 Mean fibroblast cell count on Days 1, 3, and 7 (The authors)
In the control group, the average and standard
deviation of the number of fibroblasts from the sockets
of Wistar rats treated with placebo gel (CMC-Na) on
4. Discussion
Healing post-tooth extraction wounds consists of
 107

four phases: hemostasis, inflammation, proliferation, gradually depolymerizing polymer groups to release N-
and remodeling or maturation. In the hemostasis phase, acetyl-β-D-glucosamine. This triggers GAGs secretion,
chitosan gel can shorten the bleeding time. In this accelerating the formation of GAGs-collagen bonds to
study, the bleeding time after tooth extraction in the promote granulation tissue formation and
treatment group was shorter than that in the control reepithelialization processes, leading to rapid wound
group. This aligns with Chen et al.’s [9] research on the closure [14]. This aligns with the findings of Hartono et
effectiveness of 78% deacetylated chitosan in blood al. [15], who demonstrated that chitosan gel enhances
clotting time, reporting that chitosan can form reepithelialization by stimulating the migration and
coagulation upon contact with blood. The hemostatic proliferation of inflammatory cells.
properties of chitosan come from its positive charge, In this study, aside from measuring residual socket
which can initiate the aggregation of negatively volume, an indicator for evaluating the socket closure
charged erythrocytes [10]. Adhesion and aggregation process is the number of fibroblast cells that
of erythrocytes are the initial steps of chitosan in proliferate. The one-way ANOVA test results showed a
stopping bleeding. Chitosan can cause red blood cells significant difference in the 3% chitosan gel treatment
to adhere, aggregate, and change shape, forming a group and placebo CMC-Na gel control group, with
strong blood clot that blocks the bleeding point. respective significance values of 0.000 (p<0.05). The
Chitosan has nonspecific membrane adhesion post hoc LSD test indicated a significant difference in
properties, allowing it to adhere to the wound area and the chitosan group’s fibroblast cell count between Days
interact with hemoglobin through hydrogen bonding, 1 and 3, with a significance value of p=0.001 (p<0.05).
electrostatic interactions, and hydrophobic interactions, The increase in the fibroblast cell count on Day 3 is
resulting in microstructural changes in hemoglobin and due to fibroblast proliferation induction by growth
increased viscosity [11]. In addition, the amino groups factors produced by macrophages. Chitosan contains
on chitosan molecules can create a mesh-like spatial N-acetyl glucosamine monomers that trigger
structure, enhancing interactions between blood macrophage migration and proliferation, leading to
components and chitosan, supporting the formation of a increased metabolic activity, such as the secretion of
strong blood clot [10]. VEGF, FGF, TGF, and angiopoietin, stimulating
In the inflammation phase, chitosan plays a role in fibroblast cell proliferation [12]. This is consistent with
reducing inflammation signs by enhancing the Feng et al. [14], who stated that epithelial migration
functions of inflammatory cells such as activity develops well on Day 3 and proliferating cells
polymorphonuclear (PMN) cells, macrophages, and increase. In contrast, the placebo CMC-Na gel group
fibroblasts. The N-acetyl-D-glucosamine monomer in showed no significant difference, with a significance
chitosan binds to macrophage’s main receptors, value of p=0.053 (p>0.05), because CMC-Na gel does
triggering migration and proliferation of macrophages, not contain compounds that stimulate fibroblast cell
enhancing the phagocytosis process [12]. This leads to proliferation [16].
a rapid progression of the inflammation phase and a In this study, both the chitosan gel and CMC-Na gel
decrease in the signs of inflammation. This is groups showed significant differences between Days 3
consistent with de Jesus et al.’s [13] study, which and 7 and between Days 1 and 7 (p<0.05). However,
showed that 3% chitosan hydrogel can reduce the chitosan gel group exhibits higher fibroblast cell
inflammation signs compared with the group without proliferation than the CMC-Na gel group because
chitosan. chitosan can support collagen formation, prevent scar
The post hoc LSD test results showed a tissue formation, and promote fibroblast cell formation
nonsignificant difference in the mean residual socket [17]. This study’s results indicate that 3% chitosan gel
volume between the 3% chitosan gel treatment group plays a role in accelerating socket wound closure after
on Days 1 and 3, with a significance value of p=0.158 extraction in male Wistar rats. This aligns with Gupta
(p>0.05). However, significant differences were et al.’s [18] research on the effectiveness of chitosan in
observed between Days 3 and 7 and between Days 1 accelerating wound healing after extraction.
and 7, with significance values of p=0.004 and p=0.000
(p<0.05). The non-significant difference in the RSV
between Days 1 and 3 in the 3% chitosan gel group is
5. Conclusion
The chitosan gel from black crab (Scylla serrata) is
related to the ongoing inflammation phase on Day 1,
effective in accelerating wound closure and increasing
whereas the proliferation phase begins on Day 3,
the number of fibroblasts in the socket after tooth
showing no significant differences in socket closure
extraction as part of the wound healing process. The
dimensions. The significant differences in the RSV
chitosan gel demonstrates faster wound closure than
between Days 3 and 7 and between Days 1 and 7
the control group, as observed on Days 3 and 7. In
indicate that chitosan plays a crucial role in the
addition, the chitosan gel stimulated and enhanced
proliferation phase. In this phase, chitosan amino
fibroblast cell proliferation from the first day of
groups stimulate fibroblast secretion. Stimulation
application, reaching its peak on the 7th day, in contrast
begins when chitosan contacts the oral mucosa tissue,
to the control group. This research indicates that black
 Rusdy et al. Effect of Black Crab (Scylla Serrata) Chitosan Gel on the Three-Dimensional Socket Response and Fibroblasts after Tooth
Extraction in Rattus Norvegicus, Vol. 51 No. 3 March 2024
108
crab chitosan gel (Scylla serrata) is suitable for use as [9] CHEN Z., YAO X., and LIU L. Blood Coagulation
an intervention in wound care, particularly for socket
wounds after tooth extraction. Therefore, black crab
chitosan gel as a new material for accelerating the post-
tooth extraction healing process can serve as a basis for
development in other fields of dentistry. Suggestions
for further research include conducting studies using
chitosan with different sizes and formulations. In
addition, it is essential to investigate the effectiveness
of black crab (Scylla serrata) chitosan on other cells
involved in the wound healing process.

Acknowledgment
The authors express their utmost gratitude to Prof.
Harry Agusnar as the innovator and inventor of black
crab (Scylla serrata) chitosan. The authors also
gratefully acknowledge the support provided by
TALENTA from the University of North Sumatra. This
support was essential for us to actively participate in
making a significant contribution to the advancement
of knowledge in our respective fields.

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