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Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102678

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Diabetes & Metabolic Syndrome: Clinical Research & Reviews

journal homepage: www.elsevier.com/locate/dsx

The effect of topical olive oil dressing on the healing of grade 1 and 2
diabetic foot ulcers: An assessor-blind randomized controlled trial in
type 2 diabetes patients
Aminreza Abdoli a, Roghayeh Shahbazi b, Ghazal Zoghi c, Parivash Davoodian d,
Somayeh Kheirandish c, Mohsen Azad a, Masoumeh Kheirandish c, *
a
Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
b
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada
c
Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
d
Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Background and aims: We aimed to compare the effect of topical olive oil dressing plus standard care
Received 7 February 2022 with standard care alone on the treatment of grade 1 and 2 diabetic foot ulcers (DFUs) in type 2 diabetes
Received in revised form mellitus (T2DM) patients.
5 November 2022
Methods: This assessor-blind randomized controlled trial included 60 T2DM patients with DFU referred
Accepted 17 November 2022
to the Diabetes Clinic of Shahid Mohammadi Hospital, Bandar Abbas, Iran, from February 21 to August 22,
2017. Patients were randomly assigned to intervention (n ¼ 30) and control (n ¼ 30) groups. The
Keywords:
intervention group received standard care, including wound irrigation with normal saline and oral an-
Diabetes
Diabetic foot
tibiotics plus daily topical olive oil dressing for four weeks, and the control group only received standard
Healing care. The wound healing assessment scale (wound degree, color, drainage, and surrounding tissue
Olive oil healing) was recorded weekly and the total wound status was determined at the end of the study.
Results: Treatment with olive oil led to significantly higher scores of ulcer degree, color, drainage, and
surrounding tissue healing at weeks one, two, three and four in the olive oil group than in the control
group (P < 0.001). Also, the total wound status score was higher in the olive oil group compared to the
control group (P < 0.001). The proportions of completely healed, partially healed, and unhealed wounds
were 76.6%, 23.3% and 0% in the intervention group, and 0%, 93.3% and 6.7% in the control group,
respectively.
Conclusions: Topical olive oil dressing promoted the healing of DFU and it can be recommended as a safe
and effective treatment in this regard.
Trial registration: Iranian Registry of Clinical Trials (IRCT), IRCT20150607022585N4. Registered 05/12/
2018. Retrospectively registered, https://www.irct.ir/trial/19460.
© 2022 Published by Elsevier Ltd on behalf of Research Trust of DiabetesIndia (DiabetesIndia) and
National Diabetes Obesity and Cholesterol Foundation (N-DOC).

1. Introduction neuropathy, ischemia, and infection and can lead to lower limb
amputation and prolonged hospital stay in several cases [3]. With
Type 2 diabetes mellitus (T2DM) is among the most prevalent an annual incidence rate of 25e80%, diabetic foot affects more than
chronic diseases worldwide. It is estimated that by 2045, over 629 15% of people with diabetes [4,5]. Also, the treatment of diabetic
million people will be affected by diabetes worldwide [1,2]. Dia- foot is very costly both for the afflicted individual and the society
betic foot is a significant complication of diabetes that results from [6].
In addition to conventional antidiabetic treatment, that is con-
trol of blood sugar, diabetic foot ulcer (DFU) is usually managed by
* Corresponding author. Endocrinology and Metabolism Research Center, Hor- broad-spectrum antibiotics to control the infection, and daily
mozgan University of Medical Sciences, P.O. Box: 7919915519, Bandar Abbas, Iran. wound care including debridement, antiseptic bath, and
E-mail address: kheirandishm@yahoo.com (M. Kheirandish).

https://doi.org/10.1016/j.dsx.2022.102678
1871-4021/© 2022 Published by Elsevier Ltd on behalf of Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC).
A. Abdoli, R. Shahbazi, G. Zoghi et al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102678

amputation of toes if they become gangrenous [7]. However, poor Allocation software by the study methodologist. Accordingly, a total
wound healing has been reported in patients with diabetes, with a of 60 sealed envelopes numbered from 1 to 60 were prepared by
large number of patients suffering from DFU despite standard the principal investigator, each including a group (intervention/
treatment. Unhealed DFU may lead to ulcer infection, gangrene, control). An envelope was given to each patient in order of their
amputation, and death [8e11]. Nonetheless, early and effective attendance at the Diabetes Clinic. The study protocol was approved
management of DFU can prevent the aforementioned by the Ethics Committee of Hormozgan University of Medical Sci-
complications. ences, Bandar Abbas, Iran under the ethics code: HUMS.-
The heavy cost of hospitalization for unhealed DFU and treat- REC.1396.24. The research has also been retrospectively registered
ment of its complications has led to a search for new therapeutic at the Iranian Registry of Clinical Trials (IRCT) with certificate No.:
methods. Some studies have revealed that herbal and alternative IRCT20150607022585N4, and is accessible at the following web-
medicine products such as honey, Propolis, Aloe vera, Tangzu site: www.irct.ir.
Yuyang, Astragali Radix, Rehmanniae Radix, and Semelil are
beneficial to ulcer healing [12e18]. Olive oil has also been investi- 2.2. Variables assessment
gated for the management of DFU in quite a few studies, mostly in
comparison with other agents [12,15,18e20]. The potential positive A general information questionnaire was used to collect data on
effect of olive oil on tissue blood flow and its possible anti- demographic, clinical and anthropometric characteristics of par-
inflammatory properties can be the underlying mechanisms ticipants. Data on DFU were recorded by a general physician, who
through which olive oil contributes to diabetic foot wound healing was blinded to the grouping of patients, using an ulcer healing
[21]. It has been stated by the above-mentioned studies regarding assessment checklist [21]. The checklist included data on grade,
the effect of olive oil on DFU, that further studies are required to size, site, duration, vascular and neuropathy status of the wound
confirm their results. Thus, we aimed to compare the effects of (recorded at the initial visit), wound healing assessment scale
topical olive oil dressing plus standard care with standard care (recorded on a weekly basis), total wound healing status, and
alone on DFU. adverse complications such as sensitivity, bleeding, infection, and
pain (recorded at the end of intervention). Wound grade was
2. Methods determined using Wagner's classification. Wound size was deter-
mined through measuring surface area and depth of ulcer. At
2.1. Study design baseline, the largest area and the deepest part of the wound (using
a sterile probe) were measured in millimeter. Lower-extremity
The current study was an assessor-blind randomized controlled vascular insufficiency was diagnosed based on the lack of both
trial performed on T2DM patients with DFU who were referred to dorsalis pedis and posterior tibialis pulses in the involved foot.
the Diabetes Clinic of Shahid Mohammadi Hospital, Bandar Abbas, Neuropathy was assessed based on vibration sensation using a
Iran, from February 21 to August 22, 2017. According to the sug- standard 256 Hz tuning fork (Surgicon, Germany) and pressure
gested formula for calculating the sample size in randomized sensation using a 10-g monofilament (Gima, Italy). Wound healing
clinical trials, with type I error of 1% (a ¼ 0.01), type II error of 10% assessment was performed based on four characteristics of the
(b ¼ 0.1, power ¼ 90%), and based on the mean and standard de- wound, including grade, color, surrounding tissues and drainage,
viation of wound healing scores in the intervention and control and total ulcer status was determined at the end of each week. Each
groups reported in a previous study [21], a sample size of at least 24 parameter had 100 scores, and based on the total score obtained
was calculated for each group. We allocated 30 participants to each (ranged from 50 to 400 with higher scores indicating better wound
group. Subjects were patients with T2DM who had presented with healing), status of ulcer healing was determined as complete (a
an ulcer in their lower extremities. Inclusion criteria were: T2DM, score of 400), partial (at least 30 scores increase compared to the
age of 30e65 years, 18 body mass index (BMI) 35 kg/m2, grade 1 first week) and lack of healing (no increase in wound healing
or 2 ulcer on toes, soles, heels or dorsum of the feet based on scores) at the end of intervention [21]. Furthermore, at the end of
Wagner's classification [22] for more than 4 weeks, and written each week, photographs were taken of the ulcer area for all patients
informed consent to participate in the study. Exclusion criteria to monitor the wound healing process using a digital camera.
were any history of smoking, addiction, or alcohol consumption, To improve the quality of DFU diagnosis and primary outcome
comorbidities such as cancer, chronic kidney disease, liver failure, (total ulcer status score) and secondary outcomes (individual
congestive heart failure, and vasculitis, as well as having received wound parameters, including wound color, degree, drainage, and
medications that delay ulcer healing including glucocorticoids, surrounding tissue healing) measurements, we used standard
immunosuppressive agents, and cytotoxic drugs. Patients with foot questionnaire and classification [21,22], and all variables and out-
gangrene who were candidates for amputation, patients with active comes were assessed by the same trained physician who was
infection who required intravenous antibiotic therapy, patients blinded to the grouping of patients. Furthermore, all variables and
with venous, ischemic, or traumatic ulcers, and those who failed to outcomes regarding DFU diagnosis, classification, status, and
attend the clinic for more than two consecutive follow-up visits improvement were also evaluated by an expert endocrinologist
were also excluded. Diabetes was the only underlying disease who was also unaware of the received treatment by each patient.
affecting wound healing. Other comorbidities were hypertension Anthropometric indices, including height without shoes and
and dyslipidaemia. with the precision of 0.5 cm, weight with light clothes and with the
Among 83 participants with DFU who had been referred to the precision of 100 g using Seca scale, and body mass index (BMI) by
clinic, 60 were eligible and were invited to take part in the study. dividing weight (kg) by height squared (m2) were measured at
Patient enrolment and eligibility assessments were done by the baseline. Fasting blood samples were collected once (at baseline) to
principal investigator. Details of patient enrolment, allocation, evaluate fasting plasma glucose (FPG) and glycosylated hemoglobin
follow-up, and analysis are demonstrated in Fig. 1. Participants (HbA1c) of patients. FPG was measured by the gluco-oxidase
were randomly assigned to intervention (n ¼ 30) and control method using a commercial kit (Human, Germany) and HbA1c
groups (n ¼ 30) for 4 weeks. Simple randomization was done was measured by column chromatography using a commercial kit
through randomly-generated numbers using the Random (Biosource, Spain).

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A. Abdoli, R. Shahbazi, G. Zoghi et al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102678

Fig. 1. Patients' enrollment and follow-up flow chart. Patients in the intervention group received standard care and daily dressing with topical olive oil for 4 weeks; those in the
control group received standard care and daily routine dressing at the same time.

2.3. Intervention purulent secretion [23], without wound culture. Patients with
moderate to severe wound infection were excluded from the study.
At first visit, the goals, methods of intervention and duration of Given the polymicrobial nature of diabetic ulcer infections [24], all
the project, as well as comprehensive education about DFU patients received cloxacillin for 2 weeks. We used virgin olive oil
morbidity, were fully explained to the patients. Furthermore, the (Louyeh Food Industry, Roodbar-Ganzha, Gilan), with no contami-
general and clinical characteristics of attendees were collected. DFU nation in three microbial tests. Daily follow-up phone calls were
was assessed by the same general physician for all recruited pa- made for all subjects. Weekly assessment of wound healing was
tients. During the first session, all patients were also trained about done by the same general physician (who was not aware of the
the proper dressing technique. Both groups received standard grouping of the participants) for all patients in both groups, at the
therapies and care for diabetes and foot ulcer management. Stan- recruitment center.
dard care in the control group included irrigating and cleaning the
center and periphery of ulcers with 1000 ml of sterile normal saline 2.4. Statistical analysis
solution then leaving it to dry and subsequently dressing the
wound with sterile gauze. In the intervention group, before dres- The statistical analysis of data was performed using the SPSS
sing with sterile gauze, the surface of the patient's ulcer was fully software version 25.0 (IBM Corp. Armonk, NY, USA). The indepen-
covered by olive oil using a sterile syringe and then dressing was dent t-test was used to compare the mean of continuous variables
done by sterile gauze. The olive oil used was virgin olive oil made between the two groups. The Chi-squared test was used to compare
cold-pressed and without the use of any heat or chemicals, categorical variables between groups. P-value<0.05 was considered
extracted purely mechanically, by grinding olives into a paste fol- statistically significant.
lowed by pressing. Daily dressing was done by the patients of both
groups at home. Oral antibiotics were prescribed for both groups 3. Results
based on ulcers' status and clinical diagnosis for mild to moderate
infected wounds with at least two signs or symptoms of inflam- From the 60 patients included in the current study 60% (n ¼ 36)
mation (erythema, warmth, tenderness, pain, and induration) or were female and 40% (n ¼ 24) were male. The proportions of ulcers
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A. Abdoli, R. Shahbazi, G. Zoghi et al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102678

on toes, soles, heels, and dorsum were 14 (46.66%), 9 (30%), 5 3.2. Secondary outcomes
(16.66%), 2 (6.66), respectively in the intervention group, and 12
(40%), 8 (26.66%), 7 (23.33%), 3 (10%), respectively in the control At baseline (week 0), there were no significant differences be-
group (P > 0.05). The general characteristics of patients in the tween the intervention and control groups regarding wound de-
intervention and control groups are demonstrated in Table 1. Pa- gree, color, drainage, and healing of surrounding tissue (P > 0.05).
tients in both groups were comparable regarding age, sex, occu- However, treatment with topical virgin olive oil increased the mean
pation, marital status, and education, as well as all other general scores of ulcer degree, color, drainage and surrounding tissue
characteristics (see Table 1). healing in the olive oil group compared to the control group at
weeks one, two, three and four of the study (P < 0.001) (Table 2).
None of the participants complained about adverse effects through
3.1. Primary outcome
treatment with olive oil dressing.
Pre-intervention mean of total wound status score was not
4. Discussion
statistically different between the two groups (P ¼ 0.092). At the
end of the study, although the score of total ulcer status increased
In the current study, we evaluated the effect of topical olive oil
in both the intervention and control groups compared to baseline
dressing on the healing of DFU. Findings of our study demonstrated
values, this increase was significantly higher in the olive oil group
that olive oil can be beneficial to the healing of grade 1 and 2 of
(393.33 ± 12.75) compared to the control group (240.00 ± 22.40)
DFUs. Based on our results, a significant difference was observed in
(P < 0.001). Based on the total ulcer score, complete wound healing
the total status of wound healing between olive oil group and
was observed in 76.6% subjects of the intervention group, while
control group at the end of weeks one, two, three and four, which
none of the subjects in the control group experienced complete
indicates the beneficial role of topical olive oil as an adjunct therapy
wound healing (P < 0.001). Lack of wound healing was 0% and 6.7%
for DFU.
in the intervention and control groups, respectively (P < 0.001)
Some possible mechanisms have been suggested for the thera-
(results not included in the table). The majority of subjects in the
peutic effects of olive oil. Evidence shows that olive oil might be
control group had partial wound healing (Figs. 2 and 3).
effective in wound treatment by increasing the blood flow and
reducing inflammation in damaged tissue [21]. Furthermore,
Table 1 topical olive oil promotes pressure ulcer healing by reducing
General characteristics of the intervention and control groups. oxidative damage and stimulating dermal reconstruction [21,25].
Variables Groups Essential fatty acid content of olive oil is believed to induce cell
healing [26]. Also, anti-microbial, anti-inflammatory, and antioxi-
Intervention (n ¼ 30) Control (n ¼ 30)
dant properties of olive oil have been reported in animal models
Age (years), mean ± SD 51.60 ± 9.04 52.93 ± 9.32 [26].
Sex, N (%)
The results of our study were partly similar to the results of the
Male 14 (46.7) 10 (33.3)
Female 16 (53.3) 20 (66.7) study of Nasiri et al. [21]. and Elshenawie et al. [12], who investi-
Height (cm), mean ± SD 164.42 ± 9.46 162.93 ± 10.33 gated the effects of topical olive oil dressing on the grade 1 and 2
Weight (kg), mean ± SD 72.50 ± 14.26 68.63 ± 10.68 DFUs, and the effect of ozonated olive oil ointment dressing on the
BMI (kg/m2), mean ± SD 26.80 ± 4.72 25.98 ± 4.07 healing of all grades of superficial and deep DFUs, respectively. In
Occupation, N (%)
Unemployed 18 (60.0) 21 (70.0)
Nasiri et al.’s study, the total status of wound improved at the end of
Employed 6 (20.0) 9 (30.0) weeks one, two and four of intervention, while unlike our study,
Retired 6 (20.0) 0 (0.0) they did not find a significant difference between the two groups at
Marital status, N (%) the end of week 3 [21]. On the other hand, in Elshenawie et al.’s
Married 28 (93.3) 30 (100.0)
study, a significant difference was reported between patients
Divorced 2 (6.7) 0 (0.0)
Single 0 (0.0) 0 (0.0) managed by ozonated olive oil dressing and patients managed by
Education, N (%) conventional dressing regarding ulcer healing after two, three, four,
Illiterate 3 (10.0) 2 (6.7) and five weeks [12]. Although in our study daily dressing was done
Less than high school diploma 13 (43.3) 11 (36.7) by the patients and weekly examination was performed by a gen-
High school diploma 14 (46.7) 17 (56.7)
Higher education 0 (0.0) 0 (0.0)
eral physician, wound improvement was significant like other
Duration of diabetes, N (%) studies in which daily dressing was performed by a physician
>10 years 14 (46.7) 12 (40.0) [12,21]. It appears that increasing patients' awareness and
5e10 years 8 (26.7) 6 (20.0) involving them in their DFU care has a significant impact on wound
<5 years 8 (26.7) 12 (40.0)
healing.
Comorbidities, N (%)
Hypertension 12 (36.0) 10 (30.0) In another study by Aziza et al., improvement in the wound
Dyslipidemia 23 (69.0) 20 (60.0) healing process was observed in patients receiving olive oil oint-
FBS (mg/dl), mean ± SD 193.90 ± 93.10 169.87 ± 61.58 ment at the end of week two of intervention, while in contrast with
HbA1c (%), mean ± SD 9.31 ± 2.42 8.86 ± 1.67 our results, no significant differences were reported between
Medications, N (%)
Hypoglycemic agents 20 (66.7) 17 (56.7)
treatment and control groups at weeks one, two and four [20]. The
Insulin 10 (33.3) 13 (43.3) discrepancy between the two studies can be explained by the fact
Antibiotics, N (%) that Aziza et al. included patients with both type 1 and type 2
Cloxacillin 9 (27.0) 11 (33.0) diabetes and the majority of T2DM patients were non-insulin
Ulcer gradea, N (%)
dependent. Moreover, they used ozonated olive oil. Also, the con-
Grade 1 18 (60.0) 16 (53.3)
Grade 2 12 (40.0) 14 (46.7) ventional hospital dressing was slightly different in their study as
Ulcer duration (months), mean ± SD 6.60 ± 4.56 6.73 ± 4.12 well as the assessment methods.
Abbreviations: N, number; SD, standard deviation; BMI, body mass index; FBS,
In the present study, the proportion of patients with completely
fasting blood sugar; HbA1c, glycated hemoglobin. healed, partially healed and unhealed wounds were 76.7%, 23.3%,
a
Based on Wagner Diabetic Foot Ulcer Grade Classification System. and 0%, respectively in the intervention group. Our results were to
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A. Abdoli, R. Shahbazi, G. Zoghi et al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102678

Fig. 2. Wound healing in the topical olive oil group. Figure A: Pre-intervention, Figure B: At the end of week 3, Figure C: At the end of week 4.

Fig. 3. Wound healing in the topical olive oil group. Figure A: Pre-intervention; Figure B: At the end of week 4.

Table 2
Scores of ulcer parameters and total ulcer status at baseline and at the end of the study in olive oil and control groups.

Variables Groups P-valuea

Intervention (n ¼ 30) (Mean ± SD) Control (n ¼ 30) (Mean ± SD)

Ulcer degree score week 0 29.17 ± 11.23 28.17 ± 10.46 0.723


week 1 49.17 ± 14.45 33.17 ± 9.96 <0.001
week 2 66.17 ± 11.19 39 ± 11.02 <0.001
week 3 78.50 ± 8.72 46.33 ± 11.74 <0.001
week 4 92.83 ± 6.39 53 ± 11.11 <0.001
Ulcer color score week 0 65.67 ± 5.04 65.33 ± 5.07 0.795
week 1 75.67 ± 5.04 68.67 ± 6.81 <0.001
week 2 81.67 ± 6.48 72.67 ± 6.91 <0.001
week 3 86.67 ± 4.79 75.67 ± 6.79 <0.001
week 4 97.33 ± 4.5 78 ± 7.14 <0.001
Ulcer drainage score week 0 39.67 ± 10.33 37 ± 7.94 0.266
week 1 52.67 ± 9.44 40.67 ± 6.91 <0.001
week 2 67 ± 12.36 44.67 ± 8.19 <0.001
week 3 80.33 ± 9.28 47.67 ± 8.58 <0.001
week 4 95.67 ± 6.26 51.67 ± 9.5 <0.001
Surrounding tissues healing score week 0 34.83 ± 9.24 30 ± 11.67 0.081
week 1 54.17 ± 13.52 36.67 ± 12.55 <0.001
week 2 75 ± 13.77 42 ± 10.47 <0.001
week 3 90.83 ± 9.48 49 ± 12.06 <0.001
week 4 99 ± 2.03 57.33 ± 12.51 <0.001
Total ulcer status score week 0 167.63 ± 18.13 160.50 ± 13.79 0.092
week 1 230.33 ± 17.95 178.83 ± 19.33 <0.001
week 2 290 ± 20.38 198.33 ± 17.09 <0.001
week 3 336.83 ± 16.05 220.33 ± 21.97 <0.001
week 4 393.33 ± 12.75 240 ± 22.4 <0.001
a
Analyzed by the independent t-test.

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A. Abdoli, R. Shahbazi, G. Zoghi et al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102678

some extent similar to the study of Nasiri et al. [21]. in which Mohammadi Hospital, Bandar Abbas, Iran. We also thank the
proportions of complete healing, partial healing and lack of healing Technology and Research Vice-Chancellery for funding the current
were 73.3%, 26.7 and 0%, respectively in those treated with olive oil. study under the grant ID: HUMS.REC.1396.24.
Almost identical protocol and ethnicity in our study and Nasiri
et al.'s study can justify similar findings. Elshenawie et al. [12], and References
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double-blind randomized clinical trial study in Iran. J Diabetes Metab Disord
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of foot ulcers are required to determine the effectiveness of topical [22] Wagner FW. The diabetic foot. Orthopedics 1987;10(1):163e72.
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Declaration of competing interest 2008;3(10):e3326.
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Ann N Y Acad Sci 2018;1411(1):153.
The authors declare that they have no conflict of interest.
[25] Lin T-K, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects
of topical application of some plant oils. Int J Mol Sci 2018;19(1):70.
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epithelialization of epithelial tissue in excision wound healing model in
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We would like to express our sincerest gratitude towards the [27] Karimi Z, Mousavizadeh A, Rafiei H, Abdi N, Behnammoghadam M,
patients who participated in the study and the personnel at Shahid Khastavaneh M, et al. The effect of using olive oil and fish oil prophylactic

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Cosmet Invest Dermatol 2020;13:59. tients. J Eur Acad Dermatol Venereol 2009;23(11):1298e303.
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Comparing the effect of henna oil and olive oil on pressure ulcer grade one in teriorates as the severity of diabetic foot ulcers increases and independently
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