Journal of Cranio-Maxillo-Facial Surgery 51 (2023) 772–779

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Journal of Cranio-Maxillo-Facial Surgery

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Radiographic evaluation of alveolar ridge preservation using a chitosan/

polyvinyl alcohol nanofibrous matrix: A randomized clinical study
Gamil Al-Madhagy a, Khaldoun Darwich a, Ibrahim Alghoraibi b, Essam Ahmed Al-Moraissi c, *
a
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Damascus University, Damascus, Syrian Arab Republic
b
Department of Physics, Faculty of Science, Damascus University, Damascus, Syrian Arab Republic
c
Department of Oral and Maxillofacial Surgery, Thamar University, Yemen

A R T I C L E I N F O A B S T R A C T

Handling editor: Emeka Nkenke The objective of this randomized clinical trial (RCT) was to assess the effectiveness of electrospun chitosan/
polyvinyl alcohol (CS/PVA) nanofibrous scaffolds in preserving the alveolar ridge and enhancing bone remod­
Keywords: eling following tooth extraction when compared to a control group. In this split RCT, 24 human alveolar sockets
Nanofibrous scaffold were randomly assigned to two groups, with 12 sockets receiving CS/PVA nanofibrous scaffold grafts (test group)
Chitosan
and 12 left to heal by secondary intention as the control group. Cone-beam computed tomography (CBCT) was
Alveolar ridge preservation
performed at two different time points: immediately after extraction (T0) and 4 months post-extraction (T4).
Randomized controlled trial
Cone-beam computed tomography After 4 months, linear vertical and horizontal radiographic changes and bone density of extraction sockets were
Tissue engineering assessed in both the test and control groups. The RCT included 12 patients (4 male and 8 female) with a mean age
of 24 ± 3.37 years. The test group had a significantly lower mean vertical resorption vs the control group, with a
mean difference of 1.1 mm (P < 0.05). Similarly, the control group’s mean horizontal bone resorption was − 2.01
± 1.04 mm, while the test group had a significantly lower mean of − 0.69 ± 0.41 mm, resulting in a mean
difference of 1.35 mm (P < 0.05). Furthermore, the study group exhibited a significant increase in bone density
(722.03 ± 131.17 HU) after 4 months compared to the control group (448.73 ± 93.23 HU). In conclusion, we
demonstrated within the limitations of this study that CS/PVA nanofibrous scaffold significantly limited alveolar
bone resorption horizontally and vertically and enhanced bone density in alveolar sockets after 4 months when
compared to results in the control group (TCTR20230526005).

1. Introduction site, and additional costs (Minetti et al., 2020).

Allografts are tissues donated between the same species that are
Bone possesses a remarkable inherent regenerative ability; however, otherwise genetically different, but they have several limitations,
this ability is limited in larger bone defects, known as critical-sized bone including immune rejection requiring a histocompatibility test to match
defects, during the healing period (Schmitz and Hollinger, 1986). Tooth and disease transmission, in addition to the disadvantages of autografts
extraction in dentistry results in the reduction of the alveolar process (Samandari et al., 2016). Xenografts involve donating grafts between
volume, both horizontally and vertically, with most of these changes different species (Mayer et al., 2020). In recent years, researchers have
occurring within the first 3 months post-extraction (Brkovic et al., focused on developing various biomaterials with different resorption
2012). Various methods have been used to aid bone healing, including rates that can be used as scaffolds and have an osteoconductive
bone grafts and tissue engineering (TE) (Ganapathy, 2016). advantage. Among these biomaterials, natural polymers such as
Autografts, which involve self-donation grafts from one site to collagen, silk fibroin, gelatin, chitin, and chitosan have been extensively
another of the same individual, are considered the gold standard due to studied. They can be used either alone or in combination with other
their osteogenic, osteoinductive, and osteoconductive characteristics, as natural or synthetic polymers (Kunert-Keil et al., 2011).
well as their disease-free transmission and non-antigenic reaction ad­ Tissue engineering (TE) is one of the strategies that can be applied to
vantages. However, they have limitations such as harvest site morbidity, develop new bone and to aid the regenerative ability while limiting
the quantity of harvested material, elongated healing time at the donor fibrosis. In TE, the incorporation of scaffolds that mimic the extracellular

* Corresponding author.
E-mail address: [email protected] (E.A. Al-Moraissi).

https://doi.org/10.1016/j.jcms.2023.09.020
Received 10 June 2023; Received in revised form 14 August 2023; Accepted 30 September 2023
Available online 12 October 2023
1010-5182/© 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
G. Al-Madhagy et al. Journal of Cranio-Maxillo-Facial Surgery 51 (2023) 772–779

Fig. 1. CS/PVA nanofibrous scaffold used in the current study. A-physical fom. B- shape of nanofibrous scaffold under scanning microscope at 5000× magnification
power. C- at 50.000× magnification power.

matrix (ECM), cells, and growth factors is crucial for achieving suc­ 2. Material and methods
cessful outcomes (Yen and Sharpe, 2008). Using nanofibrous polymeric
scaffolds can fulfill almost all the goals and requirements for a successful 2.1. Study design
TE scaffold. They have nanofibrous structural similarity to ECM, are
biodegradable, biocompatible, have adequate mechanical and physical A split-mouth RCT was carried out at the outpatient clinic of the Oral
properties, have interconnected porosity that allows the adhesion of and Maxillofacial Department, Faculty of Dentistry, University of
cells as well as growth factors, permit the transport of nutrients, oxygen, Damascus in Damascus, Syria, from 2021 to 2022. The institutional re­
waste products, and enhance cell-to-cell communications, have higher view board and ethical committee of Damascus University, Damascus,
surface area to volume ratios that favor cell attachment, growth and Syria, approved the proposal of this clinical trial study (No : DN-
proliferation, and can retain the shape and final tissue structural form 30082022), and informed consent was obtained from each patient
while being replaced by the regenerative tissue (Hutmacher et al., 2007; after the proposal was explained to them. The study included 12 patients
Costa-Pinto et al., 2011). (4 male and 8 female) with a mean age of (24 ± 3.37 years) who
Numerous studies have investigated the suitability of chitosan/ required extraction of at least 2 teeth in the upper jaw except molars on
polyvinyl alcohol (CS/PVA) nanofibrous scaffold as a potential candi­ both sides. A total of 24 teeth were extracted after obtaining written
date for bone TE. The biocompatibility, biodegradability, non-toxicity, approval from the patients. All included patients were checked to meet
and porous nature of CS/PVA scaffolds have been demonstrated in the American Society of Anesthesiologists (ASA) class I category and
both in vitro and in vivo studies, indicating their potential use in creating were not allergic to seafood or other components of the scaffolds used in
a three-dimensional (3D) environment similar to the ECM (Ding et al., this research. Patients with advanced and/or uncontrolled systematic
2014; Tao et al., 2020). Furthermore, chitosan possesses unique prop­ diseases, alcoholics, smokers, and pregnant or lactating women were
erties such as a positively charged surface and multifunctional chemical excluded from the study. The selection of the control and test sides was
groups, which allow it to bind and interact with a variety of materials achieved through simple randomization (ie, flipping a coin).
and proteins. It can also activate platelets to release growth factors and After the extraction of the desired teeth, the alveolar sockets of the
encourage adhesion to it, as well as initiate various biological and control group were left to heal by secondary intention while those of the
physiological interactions with other cells (Divya and Jisha, 2018). test groups were filled with CS/PVA nanofibrous scaffolds that were
Chitosan’s degradation byproducts, glucosamine and saccharides, can fabricated and characterized in the Nano laboratory of the University of
be incorporated into the formation of the new ECM’s proteoglycans and Damascus. For more details about synthesizing, characterizing pro­
glycoproteins or metabolized readily by the body (Aranaz et al., 2021). tocols, and in vitro studies of the scaffolds, please refer to our previously
To date, no previous randomized clinical trial (RCT) has evaluated published article (Al-madhagy et al., 2022) (Fig. 1).
the effects of these nanofibrous scaffolds as socket preservation mate­
rials in humans. Therefore, this RCT aimed to clinically apply a CS/PVA
2.2. Surgical procedures
nanofibrous scaffold into alveolar sockets following tooth extraction and
to assess its ability to enhance bone repair by monitoring ridge alter­
The dental procedure began by administering local anesthesia (2%
ations and bone density at two time points: immediately after tooth
lidocaine with 1:100.000 epinephrine) to the targeted teeth. Extraction
extraction (T0) and 4 months later (T4). Cone-beam computed tomog­
was performed by luxating the teeth with appropriate forceps and small
raphy (CBCT) was used to evaluate the efficacy of the scaffold, which has
elevators to minimize trauma to the alveolar sockets and soft tissues.
potential implications for future bone tissue engineering and regenera­
Gentle curettage was performed to remove any excess soft tissue and
tive applications (Aranaz et al., 2021).
pathologies, if present. The sterilized CS/PVA NF scaffolds were then
grafted into the test-group sites (12 alveolar sockets) and ensured to

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Fig. 2. Clinical steps of extraction and application of CS/PVA nanofibrous scaffold in the socket.
A- Before Extraction B- Extraction of test side. C- Extraction of control side. D- Application of CS/PVA nanofibrous scaffold. E- X-sutures for both sides.

saturate and cover with blood. Hemostasis was quickly achieved due to without adding any material. Finally, sutures were made to both sides to
the powerful hemostatic effect of chitosan. Meanwhile, the control- stabilize the scaffolds using Vicryl 0/3 reverse cutting edge. All teeth
group sides (12 alveolar sockets) were left to fill with blood only extraction was performed by the same surgeon. After the procedure,

Fig. 3. Drawing the two reference lines in different planes. A- In the Axial plane; the first line (1) passes through the pulp canals of adjacent teeth (a). B- In the
Sagittal plane; the second line (2) passes through the cementoenamel junction of adjacent teeth (b). C- In the Coronal plane; the two reference lines can be seen and
used to take the required measurements.

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Fig. 4. CONSORT Flow Diagram showing enrollment of patients during study.

patients were given written post-extraction instructions and prescribed box in the center of the alveolar process (Yosouf et al., 2021) (Fig. 3).
pain medication (paracetamol 500-mg tablets as needed). A mouth rinse
was also recommended for use starting from the second day. Patients 2.5. Statistical analysis
were asked to contact the clinic in case of any discomfort, persistent
pain, or allergic signs (Fig. 2). The sample size calculation was performed using G*Power program
v3.19.4, based on a t-test for independent samples with a significance
2.3. Radiographic assessment level of 0.05, study power of 80%, and effect size of 1.06 mm at 4
months. The estimated sample size required by the program was 12 for
The present study utilized CBCT to evaluate changes in alveolar each group, with a total of 24 sockets. The statistical analysis was con­
height, width, and density following tooth extraction. CBCT radiographs ducted by an independent researcher who was also blinded. Indepen­
were taken at the day of surgery (T0) and 4 months post-surgery (T4) dent t tests were used to assess the differences in means between the
using a PaX-i3D GREEN device (VATECH, Korea) with the same pa­ control and test groups for the measurement of height, width, and
rameters and processed using Ez3D plus software provided by the radiographic bone density separately, using SPSS program V23. A p
company. To ensure standardization and to avoid changes caused by value of ≤0.05 was considered statistically significant. This randomized
patient positioning, a reference line method was employed based on clinical study followed and was prepared according to the Consolidated
previous research by Yosouf et al. (2021). Two fixed reference lines were Standards of Reporting Trials (CONSORT) checklist (Supplemental file
determined in the axial and sagittal views, passing through the pulp 1).
canals and cemento-enamel junctions of adjacent teeth, respectively.
These reference lines were fixed in the coronal view for measurement of 3. Results
alveolar height, width, and density using the third view window.
Radiographic measurements were performed by a blinded specialist. Among of 30 patients, 24 alveolar sockets in 12 patients were
included after exclusion of 16 for different reasons (Fig. 4), with 4 male
2.4. Measuring the radiologic linear alveolar bone height and width (33.33%) and 8 female (66.66%) participants with a mean age of 24 ±
3.37 years. Of these sockets, 12 were treated with a CS/PVA nanofibrous
A standardization method was used to ensure consistency between scaffold, whereas the remaining sockets were left empty to heal through
the two time points, which involved drawing reference lines in two secondary intention. Radiographic imaging was used to measure
different views based on fixed anatomical points. The alveolar bone dimensional changes in the alveolar ridge and radiographic bone density
height was measured by drawing a line perpendicular to the reference at two time points: immediately post-extraction and after 4 months (T0,
line from the highest point of the buccal and palatal bone. Alveolar bone T4) using CBCT.
width was measured by taking two lines, the first connecting the two The mean difference in linear vertical bone height buccally between
highest points of the buccal and palatal plates (W1), and the second T0 and T4 in the control group was 2.3 ± 0.78 mm, whereas in the test
lying 2 mm beneath the first line (W2). The sum of these two lines gave group it was 1.09 ± 0.83 mm. Similarly, the mean difference in linear
the maximum bone width in the buccopalatal direction. Density was vertical bone height palatally was 1.43 ± 1.04 mm in the control group
measured using Hounsfield units by selecting a 5 × 2-mm rectangular and 0.35 ± 0.3 mm in the test group. The mean difference in overall

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Fig. 5. CBCT images of test and control groups at two different times (T0 and T4) showing the linear dimensional changes over time.

Fig. 6. Change in height buccally, palatally, and total height between control and test groups after 4 months.

vertical bone height was 1.82 ± 0.82 mm in the control group and 0.72
Table 1
± 0.43 mm in the test group (Figs. 5 and 6 and Table 1).
Descriptive statistics of the changes in ridge height after 4 months. BHD: buccal
The mean difference in linear alveolar bone width at W1 between T0
height difference, PHD: palatal height difference, THD: total height difference.
and T4 was 1.93 ± 1.17 mm in the control group and 0.63 ± 0.30 mm in
Group Sample Num. Mean SD 95% Confidence Interval the test group. The mean difference in linear alveolar bone width at W2
Lower Limit Upper Limit was 2.13 ± 1.04 mm in the control group and 0.78 ± 0.68 mm in the test
BHD Control 12 − 2.3 0.78 − 3.70 − 1.20 group. The mean difference in maximum bone width was 2.01 ± 1.04
Test 12 − 1.09 0.82 − 3.40 − 0.60 mm in the control group and 0.69 ± 0.41 mm in the test group (Figs. 5
PHD Control 12 − 1.43 1.04 − 3.80 0.00 and 7 and Table 2).
Test 12 0.35 0.30 1.00 0.00
− −
In terms of radiographic bone density, the mean difference between
THD Control 12 − 1.82 0.82 − 3.75 − 0.80
Test 12 − 0.72 0.43 − 1.90 − 0.35
T0 and T4 was 448.72 ± 93.23 HU in the control group and 722.03 ±

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Fig. 7. Change in ridge width at the different measuring points and the maximum width difference between control and test groups after 4 months.

than 0.05. The difference in means of the maximum alveolar bone width
Table 2 was 1.325 mm with a P value less than 0.05, and the difference in means
Descriptive statistics of the changes in ridge width after 4 months. WDT0: width
of the radiographic bone density was 273.31 HU with a P value less than
difference at the alveolar crest, WDT1: width difference 2 mm below the alveolar
0.05 (Tables 3 and 4).
crest, WDMax: maximum width difference.
Group Sample Mean SD 95% Confidence Interval
4. Discussion
Num.
Lower Upper
Limit Limit In this split RCT, we evaluated the effectiveness of CS/PVA nano­
WDT0 Control 12 − 1.93 1.17 − 4.60 − 0.40 fibrous scaffolds as biomaterials for socket preservation by comparing
Test 12 − 0.63 0.30 − 1.00 − 0.10 them to natural blood clot. Our evaluation of changes in ridge di­
WDT1 Control 12 2.13 1.03 3.40 0.20
− − −
mensions and bone density was conducted radiographically using CBCT,
Test 12 − 0.78 0.68 − 2.00 − 0.10
WDMax Control 12 − 2.01 1.04 − 3.90 − 0.30 to provide a relevant assessment of this biomaterial for socket preser­
Test 12 − 0.69 0.41 − 1.30 − 0.10 vation. This study is, to our knowledge, the first to evaluate the

131.17 HU in the test group (Fig. 8). To analyze the data, a Kolmogorov- Table 3
Smirnov test was applied to assess normal distribution, and an inde­ Difference in bone density in control and test groups after 4 months.
pendent Student t-test was performed to compare means between the Group Sample Num. Mean SD Std. Error Mean
control and test groups at T0 and T4 time intervals. The difference in Bone Density Control 12 448.73 93.23 26.91
means of overall alveolar bone height was 1.1 mm with a P value less Test 12 722.03 131.17 37.86

Fig. 8. Difference in radiographic bone density between control and study groups after 4 months.

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Table 4 preserved alveolar height and width with no statistically significant

Difference in all outcomes in control and test groups after 4 months. difference between them. Gholami et al. (2012) compared synthetic
t-value p- Difference in 95% confidence interval nanocrystalline HA and bovine bone minerals in preserving the socket
value means following tooth extraction and found no difference in width resorption
Lower Upper
limit limit between them. Toloue et al. (2012) compared calcium sulfate with FDBA
for ridge preservation and found no difference between them.
Alveolar bone − 4.115 0.001 − 1.10000 − 1.65444 − 0.54556
height
In a study by Cook and Mealey, two types of xenografts (bovine bone
Alveolar bone − 4.092 0.001 − 1.32500 − 1.99656 − 0.65344 xenograft vs bovine collagen sponge coated with non-sintered HA) were
width compared for ridge preservation, and no difference was found between
Bone density − 5.883 0.001 − 273.3083 − 370.257 − 176.967 them (Cook and Mealey, 2013). Although socket preservation proced­
ures are not material-specific, some materials may work better than
others, and the benefits of using such materials and techniques vary
effectiveness of CS/PVA nanofibrous scaffolds for socket preservation in
from altering the healing process to occupying the socket space, which
humans.
would improve clot stability and reduce shrinkage and contraction
Upon reviewing the dental literature, we found that our results were
(Caplanis et al., 2013). In general, the use of different materials such as
consistent with several previous studies. Iasella et al. applied tetracy­
grafting or filling material in socket preservation is better than nothing,
cline hydrated freeze-dried bone allograft (FDBA) and a collagen
and research is ongoing to find novel materials and techniques to limit
membrane to alveolar sockets and compared it to spontaneous healing,
bone resorption and to enhance bone augmentation (Mertens et al.,
and they found that more resorption occurred in the control group in
2019).
terms of width and height (Iasella et al., 2003). Barone et al. compared
the current study has a several limitations including: 1) This study
corticocancellous porcine bone to spontaneous healing and found that
has a relatively small sample size, which could affect the results and may
the test group had limited bone resorption, with more resorption
cause bias.; 2)It also lacks histomorphological evaluation, which could
occurring in width than in height (Barone et al., 2008). Also, Neiva et al.
give us details about bone remodeling and the reaction to CS/PVA
used a putty-form hydroxyapatite (HA) matrix combined with synthetic
nanofibrous scaffolds in humans. Moreover, it is strongly recommended
cell-binding peptide P-15 to study ridge alterations in comparison to
to conduct clinical evaluations of CS/PVA nanofibrous scaffolds after
empty sockets, and found that the test group had less resorption in
both conventional and immediate implant placement, and to compare
height than the control group but that both groups experienced more
them with various bone substitutes. This would be a valuable avenue for
bone resorption in width (test: 1.31 ± 0.96 mm; control: 1.43 ± 1.05
future research.
mm), which differed from our findings in which there was a significant
difference between the test and control groups in terms of width
5. Conclusion
resorption (Neiva et al., 2008). Similarlry, Ezoddini-Ardakani et al.
studied the effect of chitosan on dental bone repair vs spontaneous
In conclusion, this RCT using a split-mouth technique has demon­
healing and concluded that the test group exhibited more bone density
strated that CS/PVA nanofibrous scaffold as a graft material for socket
and faster bone healing than the control group (Ezoddini-Ardakani et al.,
preservation following tooth extraction can lead to a statistically sig­
2011). Furthermore, Cardaropoli et al. studied ridge alterations using
nificant reduction in bone resorption in both vertical and horizontal
bovine bone mineral with porcine collagen membrane vs tooth extrac­
planes as well as increase in radiographic bone density after a 4-month
tion alone, and found that there was less bone resorption in width and
follow-up. However, it cannot completely prevent bone resorption
height in the test group than in the control group (Cardaropoli et al.,
associated with tooth removal due to physiological shrinkage of the
2012).
alveolar socket. The use of CS/PVA nanofibrous scaffold may stabilize
Finally, Yosouf et al. (2021) conducted a study to compare alveolar
the clot and alter the healing process to promote bone preservation. It is
ridge alterations utilizing bioresorbable collagen/HA allograft vs empty
recommended that larger sample-size studies with histomorphological
sockets and found statistically significant differences in width, height,
analysis should be conducted to further evaluate the efficacy of CS/PVA
and bone density between the test and control groups.
nanofibrous scaffolds and to eliminate any potential bias resulting from
However, our results were inconsistent with the findings of Camargo
the small sample size.
et al. and Brownfield and Weltman. Camargo et al. (2000) evaluated
alveolar changes by using bio-active glass vs extraction alone and found
Authors contribution statement
no difference between groups in height and width. This could be due to
the technique that they used (advanced flaps), which favored bone
Gamil Al-Madhagy: concept/design, data analysis/interpretation,
resorption on both the control and experimental sides.
drafting article, and approval of article, statistics. Khaldoun Darwich:
Addtionally,Brownfield and Weltman (2012) studied alveolar ridge
concept/design, data analysis/interpretation, drafting article, critical
alterations between osteoinductive demineralized bone matrix with
revision of article, and approval of article. Ibrahim Alghoraibi: concept/
cancellous bone chips vs extraction alone, and found that both groups
design, data analysis/interpretation, drafting article, and approval of
lost similar amounts of bone with no significant statistical difference
article. Essam Ahmed Al-Moraissi: concept/design, data analysis/inter­
between the two groups. The authors attributed that to using the
pretation, drafting article, critical revision of article, and approval of
atraumatic surgical technique with the periotomes without soft tissue
article.
manipulation, which aided in the preservation of the blood supply, and
to the inclusion criteria of intact buccal plates with four-wall sockets
Declaration of Competing interest
with retained adjacent teeth, which is an ideal and predictable defect for
regeneration, and thus the addition of bone grafts to the sockets were not
No conflict of interest.
necessary.
There are numerous studies that have compared the efficacy of
Appendix A. Supplementary data
grafting the alveolar with different biomaterials with each other. Mardas
et al. (2010, 2011) compared two types of bone grafts, synthetic bone
Supplementary data to this article can be found online at https://doi.
substitute containing β-tricalcium phosphate (β-TCP) with HA and
org/10.1016/j.jcms.2023.09.020.
deproteinized bovine bone mineral xenograft (DBBM), using membranes
in both groups; the authors concluded that both materials partially

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