Systematic Reviews Open Access
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2018; 9(10): 172-179
Published online Oct 15, 2018. doi: 10.4239/wjd.v9.i10.172
Topical application of platelet-rich plasma for diabetic foot ulcers: A systematic review
Takashi Hirase, Department of Orthopaedic Surgery, Houston Methodist Hospital, Houston, TX 77030, United States
Eric Ruff, Department of Plastic and Reconstructive Surgery, University of Texas Medical Branch, Galveston, TX 77555, United States
Salim Surani, Department of Medicine, Pulmonary, Critical Care and Sleep Medicine, Texas A and M University, Corpus Christi, TX 77807, United States
Iqbal Ratnani, Department of Anesthesiology and Critical Care, Houston Methodist Hospital, Houston, TX 77030, United States
ORCID number: Takashi Hirase (0000-0001-9111-0667); Eric Ruff (0000-0002-5084-8865); Iqbal Ratnani (0000-0002-1168-3041); Salim Surani (0000-0001-7105-4266).
Author contributions: Hirase T and Ruff E designed the research; Hirase T and Ruff E performed the research; Hirase T analyzed the data; Hirase T and Ruff E wrote the paper; Surani S and Ratnani I supervised the paper; all authors read and approved the final manuscript.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Salim Surani, FACC, FACP, MD, Adjunct Clinical Professor, Department of Medicine, Pulmonary, Critical Care and Sleep Medicine, Texas A and M University, 701 Ayers street, Corpus Christi, TX 77807, United States. srsurani@hotmail.com
Telephone: +1-361-8857722 Fax: +1-361-8857792
Received: May 2, 2018
Peer-review started: May 3, 2018
First decision: June 8, 2018
Revised: June 15, 2018
Accepted: June 28, 2018
Article in press: June 28, 2018
Published online: October 15, 2018

Abstract
AIM

To determine if topical application of platelet-rich plasma (PRP) to diabetic foot ulcers (DFUs) results in superior healing rates.

METHODS

A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level I-IV investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were “platelet rich plasma”, “diabetes”, “ulcers”, and “wound”. The Modified Coleman Methodology Score (MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.

RESULTS

One thousand two hundred and seventeen articles were screened. Eleven articles (322 PRP subjects, 126 controls, PRP subject mean age 58.4 ± 7.2 years, control mean age 58.7 ± 5.9 years) were analyzed. Six articles were level II evidence, four were level III, and one article was level IV. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls (0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). Mean heal time to > 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively (P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls (7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P < 0.001).

CONCLUSION

The topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls.

Key Words: Platelet rich plasma, Diabetes, Foot, Ulcer, Wound

Core tip: There is growing evidence supporting the use of autologous platelet-rich plasma (PRP) to enhance the healing process of diabetic foot ulcers (DFUs). This systematic review of eleven articles (322 PRP subjects, 126 controls) showed that healing rate was significantly faster with PRP application compared to controls (0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). There were significantly lower adverse effects reported with PRP application compared to controls. The authors conclude that the topical application of PRP for DFUs results in statistically superior healing rates compared to controls with lower complication rates.
INTRODUCTION

Diabetic foot ulcers (DFUs) are among the most common complications of diabetes mellitus with a lifetime incidence of up to 15% among the diabetic population[1]. Studies have shown that up to 80% of patients with DFUs suffer from both limb ischemia and peripheral neuropathy simultaneously[2,3]. These conditions further delay healing of DFUs, predisposing to higher rates of complications such as cellulitis and osteomyelitis[4]. In spite of the high prevalence and morbidity associated with DFUs, current treatment options are limited. Current standard management consists of surgical debridement followed by frequent dressing changes with tight infection and glycemic control. Despite this comprehensive approach, complication and amputation rates remain high[5].

In recent years, the use of autologous platelet-rich plasma (PRP) has emerged as an adjunctive method for treating DFUs[6-16]. PRP is derived from centrifugation of whole blood, which separates into 3 layers: platelet poor plasma, platelet rich plasma, and red blood cells. Contained within these platelets are a number of hemodynamically active proteins that aid in the natural process of wound healing. Specifically, the platelet alpha-granules contain several of these molecules, including: platelet derived growth factor (PDGF), TGF-β, vascular endothelial growth factor (VEGF), epithelial growth factor (EGF), fibrinogen, fibronectin, and vitronectin[17-19]. In addition, platelet delta granules contain serotonin, histamine, dopamine, calcium, and adenosine, which act in tandem with the aforementioned growth factors to regulate wound healing[20]. With increasing knowledge about the pathophysiology of refractory DFUs, alterations to the local microenvironment with PRP could play an important role in mitigating the morbidity associated with these chronic wounds.

Current studies evaluating the outcomes of topical autologous PRP on diabetic foot ulcers are limited to small randomized controlled studies and case reports. Given that there are numerous confounding variables involved with PRP use, there has been significant challenge in generating standardized protocols for patient use. Thus, the purpose of this investigation was to summarize the clinical outcomes of the topical application of autologous PRP among patients with DFUs and to determine if the method results in statistically superior outcomes compared to patients receiving conventional wound care. The authors hypothesized that the procedure results in statistically superior outcomes compared to patients receiving conventional wound care with low complication rates.

MATERIALS AND METHODS

A systematic review was registered with PROSPERO on March 9, 2017 (ID: CRD42018090780). Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed[21]. Inclusion criteria consisted of Level I-IV [via Oxford Centre for Evidence Based Medicine (CEBM)] therapeutic studies that investigated outcomes of topical applications of autologous PRP for diabetic foot ulcers among adult human patients[22]. Studies that included non-diabetic etiology of foot ulcers and use of non-autologous PRP were excluded. Cadaveric studies, basic science and animal studies, diagnostic studies, economic studies, prognostic studies, Level V evidence expert opinion, letters to editors, and review articles were excluded. Studies published in non-English languages were not excluded but were unidentified in the medical databases. In the event of different studies with duplicate subject populations, the study with the longer follow-up, higher level of evidence, greater number of subjects, or greater clarity of methods and results was included. The authors conducted separate searches of the following medical databases: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials databases. Under the PROSPERO registration, similar prior systematic reviews and meta-analyses were sought and none were identified. The searches were performed on March 8, 2017. The search terms used were “platelet rich plasma”, “diabetes”, “ulcers”, and “wound”. The search results were reviewed for duplicates and the inclusion criteria to determine articles that were included in the final analysis (Figure 1).

Figure 1
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Figure 1 Flow diagram summarizing the literature search, screening, and review. PRP: Platelet-rich plasma.

Two authors independently reviewed all articles. The study design, patient populations, and procedure technique were first identified. A weighted mean of the demographics (No. of patients, age, % female gender, duration of diabetes, duration of ulcer, HbA1c, and ulcer area) between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance. All reported outcome scores and complication rates were analyzed. The levels of evidence were then assigned based on the Oxford Centre for Evidence Based Medicine[22]. Study methodological quality was analyzed using the Modified Coleman Methodology Score (MCMS)[23]. The overall Strength-of-Recommendation Taxonomy (SORT) score was B and Grading of Recommendations Assessment, Development and Evaluation (GRADE) score was C[24,25]. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Thus, a best-evidence synthesis was used instead[26]. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.

RESULTS

One thousand two hundred and seventeen articles were screened (Figure 1). Eleven articles were included in the analysis (Table 1)[6-16]. Six articles were level II evidence, four were level III, and one article was level IV. According to MCMS, three articles were good (scores between 70 to 84), seven articles were fair (scores between 55 to 69), and one article was poor (scores less than 55). The mean MCMS was 61.8 ± 7.3. There were 465 patients analyzed. 322 patients were under the PRP group and 126 patients were under the control group (standard dressing changes ± placebo gel). There were 206 males and 87 females (29 unidentified) in the PRP group and 72 males and 39 females (15 unidentified) in the control group (P = 0.407). Mean follow-up was 10.4 ± 3.1 wk. The mean ages were 58.4 ± 7.2 years and 58.7 ± 5.9 years under the PRP and control groups, respectively (P = 0.678). The mean HbA1c were 7.94 ± 1.30 and 8.74 ± 1.08 under the PRP and control groups, respectively (P < 0.001). The mean baseline ulcer areas were 7.7 ± 9.3 cm2 and 4.6 ± 6.6 cm2 under the PRP and control groups, respectively (P = 0.689).

Table 1 Study demographics.
Mohammadi et al[6] 2017Ahmed et al[7] 2017Perez-Zabala et al[8] 2016Saad et al[9] 2011Kakagia et al[10] 2007Driver et al[11] 2006Li et al[12] 2015Saldalam-acchia et al[13] 2004Motolese et al[14] 2015Shan et al[15] 2013Kontopodis et al[16] 2016Weighted (mean ± SD)[6]P-value (PRP vs control)
Type of StudyPURPCSRPRPRDBPRPRPPUPURUN/AN/A
Level of evidenceIIIIIIVIIIIIIIIIIIIIIIIIIIN/AN/A
No. patients
PRP7028212171959715217229.3 ± 25.40.104
ControlN/A28N/A12N/A21587N/AN/AN/A25.2 ± 20.0
Age (mean ± SD, yr)
PRP53.8 ± 10.643.2 ± 18.265.5 ± 2.1NR57.0 ± 12.058.3 ± 9.761.4 ± 13.161.1 ± 9.452.3 ± 11.366.5 ± 10.86558.4 ± 7.20.678
ControlN/A49.8 ± 15.4N/ANRN/A55.9 ± 8.164.1 ± 9.458.1 ± 7.8N/AN/AN/A58.7 ± 5.9
Female gender, n (%)
PRP12 (17.1)8 (28.6)0 (0.0)NRNR3 (15.8)22 (37.3)4 (57.1)11 (73.3)13 (61.9)14 (19.4)29.70%0.407
ControlN/A10 (35.7)N/ANRN/A5 (23.8)20 (34.5)4 (57.1)N/AN/AN/A35.10%
Duration of diabetes (mean ± SD, yr)
PRP16.2 ± 7.9NR23.5 ± 13.4NRNRNR7.5016.3 ± 7.938.206.8 ± 6.7NR14.1 ± 11.60.048
ControlN/ANRN/ANRN/ANR10.0019.7 ± 9.9N/AN/AN/A11.0 ± 6.9
Duration of ulcer (mean ± SD, wk)
PRP19.6 ± 4.712.5 ± 1.028.3 ± 9.5NR19.0 ± 8.0NR4.28NRNR10.1 ± 12.0NR13.0 ± 8.4< 0.001
ControlN/A11.5 ± 2.8N/ANRN/ANR3.30NRN/AN/AN/A6.0 ± 5.8
HbA1c (mean ± SD)
PRP6.2 ± 0.77.0 ± 0.59.4 ± 3.3NR8.1 ± 2.87.8 ± 1.59.8 ± 3.19.5 ± 1.7NR9.1 ± 2.2NR7.9 ± 1.3< 0.001
ControlN/A6.9 ± 0.6N/ANRN/A8.1 ± 1.89.808.8 ± 1.7N/AN/AN/A8.7 ± 1.2
Ulcer area (mean ± SD, cm2)
PRP6.11 ± 4.376.24 ± 0.910.25NR28.4 ± 13.63.4 ± 4.54.1027.3 ± 15.613.9214.0 ± 32.34.1 ± 3.97.7 ± 9.3< 0.001
ControlN/A5.72 ± 0.8N/ANRN/A3.6 ± 4.02.9017.0 ± 8.9N/AN/AN/A4.6 ± 6.6
N/A: Not applicable; PU: Prospective uncontrolled; RP: Randomized prospective; CS: Case series; RDBP: Randomized double-blind prospective; RU: Retrospective uncontrolled; NR: Not recorded; PRP: Platelet-rich plasma.

Most studies prepared PRP through a single or double spinning approach and utilized Thrombin, CaCl2, and/or calcium gluconate as activator (Table 2). Four studies reported the amount of PRP gel applied to the wound, and two studies reported platelet concentration. Only one study reported WBC count in the final PRP prepared.

Table 2 Platelet-rich plasma preparation.
StudyMohamm-adi et al[6] 2017Ahmed et al[7] 2017Perez-Zabala et al[8] 2016Saad et al[9] 2011Kakagia et al[10] 2007Driver et al[11] 2006Li et al[12] 2015Saldalam-acchia et al[13] 2004Motolese et al[14] 2015Shan et al[15] 2013Kontopodis et al[16] 2016
PRP spinning approachSingleDoubleSingleDoubleNRSingleDoubleNRSingleSingleSingle
Duration of spin (min)105 and 57NRNR1.54 and 6NR1710NR
CompanyArya Mabna Tashkhis Co, IranNRNRNRBiomet Biologics, Warsaw, IN, United StatesCytomedix, Rockville, MD, United StatesNRNRThermogenesis, Rancho Cordova, CA, United StatesHaemonetics Corp, Braintree, MA, United StatesRegenLab, Le Montsur-Lausanne, Switzerland
PRP activatorCaCl2Thrombin, CaCl2CaCl2Thrombin, CaCl2ThrombinThrombinThrombin, calcium gluconateNRThrombin, CaCl2Thrombin, calcium gluconateNR
PRP amount applied2 mL/cm27 mL3 mLNRNRNRNRNR5 mLNRNR
Platelet concentrationNR1.0 × 106/mL-1.2 × 106/mL1.6-1.7 x baselineNRNRNRNRNRNRNRNR
WBC concentrationNRNRUndetectableNRNRNRNRNRNRNRNR
PRP application methodPRP gel applied on ulcers after irrigation and debridement every week covered with non-absorbing wet dressingPRP gel applied on ulcers after irrigation with 0.9% saline twice weekly covered with non-absorbing dressingPRP gel applied on ulcers after irrigation twice weekly covered with foam dressingsPRP gel applied on ulcers within half an hour after preparation followed by Vaseline gauze and dressing changed every 3-4 dPRP gel applied on ulcers covered with vapor-permeable film (Tegaderm, 3M)PRP gel applied on ulcer with contact layer dressing covered with non-absorbent foam dressing changed every 3-4 dPRP gel applied on ulcer after irrigation and debridement covered with Suile dressing changed every 3 d. PRP gel reapplied up to 5 times in 12 wk period if wound area reduction rate < 80%Weekly topical application of PRP gel with covered with standard dressing changed weekly5 mL of PRP gel applied on ulcers once a week for total of 10 wk covered with non-adherent dressing and bandagePRP gel applied on ulces twice per week covered with occlusive dressing changed every 72 hPRP gel applied on ulcer twice weekly after irrigation and debridement covered with standard dressings
NR: Not recorded; PRP: Platelet-rich plasma.

Eight studies assessed the time to > 90% ulcer area healing and seven studies assessed healing rate per week (Table 3). Both outcome measures were included in the best evidence synthesis. Other outcome measures included percent of ulcer completely healed at 8 and/or 12 wk follow-up (6 of 11 studies), comparison of ulcer area at baseline and at final follow-up (2 of 11 studies), Resvech 2.0 measurement score at baseline and at final follow-up (1 of 11 studies), and percent of wound length/width/depth decrease at final follow-up (1 of 11 studies).

Table 3 Platelet-rich plasma group individual study outcome measures.
StudyMohamm-adi et al[6] 2017Ahmed et al[7] 2017Perez-Zabala et al[8] 2016Saad et al[9] 2011Kakagia et al[10] 2007Driver et al[11] 2006Li et al[12] 2015Saldalam-acchia et al[13] 2004Motolese et al[14] 2015Shan et al[15] 2013Kontopodis et al[16] 2016
Ulcer area (mean ± SD, cm2)Baseline6.11 ± 4.376.24 ± 0.910.3NR28.4 ± 13.63.4 ± 4.54.127.3 ± 15.613.914.0 ± 32.34.1 ± 3.9
FinalNR1.44NRNRNRNRNR8.0 ± 7.5NRNRNR
Ulcer healed, n (%)8 wkNR23 (82.1)NRNR2 (11.8)NRNRNRNRNRNR
12 wkNR24 (85.7)NRNRNR13 (68.4)50 (84.8)NRNR15 (71.4)NR
Resvech 2.0 measurementBaselineNRNR13.5 ± 0.7NRNRNRNRNRNRNRNR
FinalNRNR6.0 ± 1.4NRNRNRNRNRNRNRNR
% wound length decreaseNRNRNRNR14.3 ± 7.1NRNRNRNRNRNR
% wound width decreaseNRNRNRNR17.4 ± 8.0NRNRNRNRNRNR
% wound depth decreaseNRNRNRNR34.9 ± 9.9NRNRNRNRNRNR
Time to > 90% ulcer area healing (mean ± SD, wk)8.7 ± 3.9NR7.0 ± 2.811.5NR6.405.1NR12.77.17 ± 5.6611.0 ± 4.0
Healing rate per week (mean, cm2)0.7NR1.46NRNR0.530.8NR1.11.950.37
Adverse effects02 – wound infections0001 – contact dermatitis5 – wound infections0000
NR: Not recorded.

Mean heal time to > 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively (Table 4; P = 0.115). Mean healing rate was significantly faster with PRP application compared to controls (0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). There were 8 (2.5%; 7 wound infections, 1 contact dermatitis) and 15 (10.5%; 14 wound infections, 1 maceration) adverse effects reported within the PRP group and control groups respectively (P < 0.001).

Table 4 Average study outcome measures included in best evidence synthesis.
Time to > 90% ulcer area healing (mean ± SD, wk)Healing rate per week (mean ± SD, cm2)Adverse effects
PRP7.8 ± 2.70.68 ± 0.568 (2.5)
Control8.3 ± 3.70.39 ± 0.0915 (10.5)
P-value0.115< 0.001< 0.001
PRP: Platelet-rich plasma.
DISCUSSION

It was determined that the topical application of PRP for DFUs resulted in statistically superior healing rate compared to patients receiving conventional wound care with low complication rates. This confirmed the authors’ hypothesis that patients receiving this treatment results in significantly superior outcomes compared to patients receiving conventional wound management. To our knowledge, this is the first systematic review to evaluate the outcomes of topical application of PRP versus conventional management of DFUs.

All studies analyzed topical application of PRP gel to improve healing of DFUs. One of the analyzed studies by Kakagia et al[10] also utilized a biomaterial consisting of collagen and oxidized regenerated cellulose. This biomaterial designed to modify the chronic wound environment through the inactivation of proteases, free radicals and metal ions has previously been shown to be an efficient method in the management of DFUs[27,28]. The authors found that the topical application of both the biomaterial and PRP on DFUs significantly enhances the healing rate compared to the biomaterial or PRP alone.

Various types of PRP systems exist with variable platelet, leukocyte, and growth factor concentrations. Chronic inflammatory response against foreign invaders are made possible by leukocytes including lymphocytes, monocytes, neutrophils, eosinophils, and basophils. Recent evidence has shown that leukocyte levels within PRP may have controversial effects on wound healing[29]. Of the studies included in the review, Perez-Zabala et al[8] reported using leukocyte-poor PRP with high average healing rates 1.46 cm2/wk. However, this review was unable to develop conclusions regarding outcome differences in the use of leukocyte-rich versus leukocyte-poor PRP as no other reviewed studies reported leukocyte levels.

Complication rates after the topical application of PRP were low. Besides the 2.2% incidence of transient wound infections and 0.3% incidence of contact dermatitis no other adverse effects were reported. The complication rates were significantly lower compared to the 11.1% incidence of wound infection and 0.8% incidence of skin maceration among patients receiving conventional wound treatment. Overall, this study demonstrates that the topical application of PRP for DFUs lead to more superior clinical outcomes compared to conventional treatment methods with lower complication rates. However, further higher quality studies with randomized controlled trials are necessary to justify the use of PRP over more cost-effective treatment methods.

There are several limitations among the studies included in this review. Five of the 11 articles were levels III or IV evidence, which limits the strength of the results. Only one of the studies used a double-blinded approach producing potential bias. The average study methodological quality as assessed by the MCMS was fair. Assimilation of heterogeneous low methodological quality studies with healing rates is a significant limitation. However, the authors minimized this as much as possible with strict study eligibility and inclusion criteria, despite the level III and IV evidence nature of the studies. Furthermore, the heterogeneity of outcome measures used among the studies limited the data analysis to two outcome measures. Another limitation of this review is that most reviewed studies did not include relevant baseline comorbidities including pre-existing peripheral arterial obstructive disease nor baseline home medications and were unable to be compared in this review. Future studies can improve through designing more prospective comparative trials, increasing study sizes, and standardizing clinical outcome measures such as healing rates, percentage of ulcers completely healed, and ulcer area at baseline and final follow-up. Another possible limitation of this review is that other relevant studies on this topic could have been excluded, despite conducting a systematic search.

In conclusion, topical application of autologous PRP for DFUs results in statistically superior healing rates compared to controls with lower complication rates. Further randomized controlled studies that show clinical outcome improvement in multiple parameters are necessary to evaluate the true efficacy of this treatment.

ARTICLE HIGHLIGHTS
Research background

Diabetic foot ulcers (DFUs) are among the most common complications of diabetes mellitus but current treatment options are limited. Current standard management consists of surgical debridement followed by frequent dressing changes with tight infection and glycemic control. In recent years, the use of autologous platelet-rich plasma (PRP) has emerged as an adjunctive method for treating DFUs.

Research motivation

Because current studies evaluating the outcomes of topical autologous PRP on diabetic foot ulcers are limited to small randomized controlled studies and case reports. Given that there are numerous confounding variables involved with PRP use, there has been significant challenge in generating standardized protocols for patient use.

Research objectives

The objective was to determine if topical application of platelet-rich plasma (PRP) to diabetic foot ulcers (DFUs) results in superior healing rates. The significance of realizing this objective combined with future research consisting of further randomized controlled studies will help evaluate the true efficacy of this treatment.

Research methods

This review was registered with PROSPERO and performed using PRISMA guidelines. Level I-IV investigations of topical PRP application in DFUs were sought in multiple databases, i.e., MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were “platelet rich plasma”, “diabetes”, “ulcers”, and “wound”. The Modified Coleman Methodology Score (MCMS) was used to analyze study methodological quality.

Research results

One thousand two hundred and seventeen articles were screened, eleven articles were analyzed, six articles were level II evidence, four were level III, and one article was level IV. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls (0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). Mean heal time to > 90% of the original ulcer area for patients in the PRP group was significantly lower with control groups (7.8 ± 2.7 wk vs 8.3 ± 3.7 wk, P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls (7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P < 0.001).

Research conclusions

We find that the topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls. This study proposes the new theory that the use of PRP is a superior option to treating DFUs than the current standard of care. A new hypothesis that may be proposed from this study is that the use of PRP results in clinical outcome improvement in multiple parameters. Combining the findings within this study with future research consisting of further randomized controlled studies that show clinical outcome improvement in multiple parameters will provide adequate evaluation of the true efficacy of this treatment.

Research perspectives

The assimilation of heterogeneous studies allowed the development of a high quality systematic review that analyzes two outcome measures. Future studies can improve through designing more prospective comparative trials, increasing study sizes, and standardizing clinical outcome measures such as healing rates, percentage of ulcers completely healed, and ulcer area at baseline and final follow-up.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Endocrinology and metabolism

Country of origin: United States

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P- Reviewer: Chang ST, Kita K, Zhou M S- Editor: Ma YJ L- Editor: A E- Editor: Bian YN

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