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Received: 24 September 2022 Accepted: 28 November 2022
DOI: 10.1111/iwj.14047

ORIGINAL ARTICLE

Research trends on platelet-rich plasma in the treatment of

wounds during 2002–2021: A 20-year bibliometric analysis

Honghao Lai 1,2,3 | Guangping Chen 1 | Wei Zhang 2 | Guosheng Wu 2 |

1,2
Zhaofan Xia

1
Department of Burn, Zhujiang Hospital,
Southern Medical University,
Guangzhou, China
2
Department of Burn Surgery, Changhai
Hospital, Naval Medical University,
Shanghai, China
3
Research Institute, Guangzhou Eighth
People's Hospital, Guangzhou Medical
University, Guangzhou, China
Correspondence
Zhaofan Xia MD, PhD, Zhujiang Hospital,
Southern Medical University, Guangzhou,
510280, Guangdong, China.
Email: xiazhaofan_smmu@163.com
Guosheng Wu MD, PhD, Changhai
Hospital, Naval Medical University,
Shanghai, 200433, Shanghai, China.
Email: 18019359841@163.com
Funding information
National Natural Science Foundation of
China, Grant/Award Number: 81901960;
Shanghai Hospital Development Center,
Grant/Award Number: SHDC2020CR4100
Abstract
Platelet-rich plasma (PRP) has attracted attention because of its potential to
accelerate the wound healing process. However, resources for evaluating research
trends in the treatment of wounds with PRP were limited. In this study, we aimed
to make a bibliometric analysis of the literature related to PRP in the treatment of
wounds and explore the research status, hotspots and frontiers in this field in
recent 20 years. Studies about PRP treatment for wounds from 2002 to 2021 were
retrieved from the Science Citation Index Expanded (SCI-E) of Web of Science
(WOS) database. Visualisation softwares such as VOSviewer and SCImago Gra-
phica, and CiteSpace were used to analyse the research trends and features. A total
of 1748 studies were identified in the SCI-Expanded from 2002 to 2021. The num-
ber of publications on PRP in the treatment of wounds has shown an increasing
trend, from 6 (in 2002) to 228 (in 2021). The papers published in the United States
have led in times cited (14637) and H-index (63). Though Italy was slightly lower
than China in the number of publications, the H-index and average cited
(47, 28.45) were higher than that of China (38, 27.01). The strongest keyword was
“fibrin” (strength = 13.07), and the longest burst duration keyword was “thrombin”
(began in 2002 and ended in 2014). The largest 10 co-citation clusters are as follows:
endothelial cell proliferation (#0), regenerative medicine-associated treatment (#1),
diabetic wound healing (#2), autologous derived (#3), platelet-rich fibrin (#4), tis-
sue engineering (#5), regenerative potential (#6), clinical randomised trial (#7), his-
tologic observation (#8), and wound bacteria (#9). The United States has made the
most outstanding contribution in this field. Chinese researchers need to enhance
the quality of publications further. Wound Repair Regen. is the most noteworthy
journal. The mechanism of growth factors of PRP, combination therapy, prepara-
tion of PRP, and related clinical trials may be topics that need attention.

KEYWORDS
bibliometric analysis, platelet-rich plasma (PRP), ulcer, visualisation, wound

Honghao Lai and Guangping Chen contributed equally to this work.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes.
© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.

Int Wound J. 2022;1–11. wileyonlinelibrary.com/journal/iwj 1

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2 LAI ET AL.

Key Messages
• we use visualisation software to show the development of PRP therapy for
wounds in the past 20 years
• visualisation softwares such as VOSviewer and SCImago Graphica, and Cite-
Space were used to analyse the research trends and features
• our research summarised hot research directions and information, such as
the strongest citation burst keywords and clusters
• the mechanism of growth factors of PRP, combination therapy, preparation
of PRP, and related clinical trials may be topics that need attention

1 | INTRODUCTION However, there was a lack of systematic evaluation of

Wound healing is a pathophysiological process of regen-
eration, repair, and reconstruction after the loss of skin
and tissue caused by injury.1 It strongly depends on many
factors, including physical conditions such as age and
nutrition, complications such as hypertension and diabe-
tes, and drugs.2,3 In recent years, some studies have
believed that psychological intervention could also affect
the effect of wound healing.4 All factors mentioned above
showed that wound healing would focus on surgery, skin
management, and clinical treatment. It was also proved
that wound healing needs various growth factors to be
involved in the regulation.5 However, there is still a lack
of effective, applicable, and economic growth factor prod-
ucts in clinical practice. Nowadays, platelet concentrate
products might provide a possible therapy choice for
wound healing.6
Platelet-rich plasma (PRP) is an autologous blood
product concentrate prepared by centrifugation mainly
composed of platelets, fibrin, and leukocytes.7 As PRP is
rich in various types of growth factors from the body
itself, concerns about immune resistance and rejection
are a non-issue.8 Furthermore, PRP indeed has the
potential to be widely used in the medical field due to
the advantages of low cost, high safety, easy extraction,
and so on. Whitman and Marx took the lead in applying
PRP in the treatment of bone tissue repair in the 1990s,
even as a drug/cell carrier for controlled release and
achieved positive effects.9,10 In decades, PRP has been
gradually used in dermatology, orthopaedics, and plastic
surgery, particularly in treating all kinds of chronic and
refractory wounds.11 Some studies have suggested that
PRP can promote the connection of microcirculation,
inhibit inflammation and reduce the rate of apopto-
sis.12-14 Yuliya Menchisheva has confirmed the substan-
tially positive effects of the PRP by applying it to the
treatment of wounds within a month in a clinic.15
At present, some qualified medical institutions and hos-
pitals have developed PRP technology for wound treat-
ment, which constantly supporting the effectiveness.
published researches.
This study mainly aimed to explore status and hot
issues of PRP in the treatment of wounds. Therefore,
we visually analysed the researches from the database
using VOSviewer (Version 1.6.18), SCImago Graphica
(Version 1.0.24), CiteSpace (Version 6.1.R3), and other
softwares.
2 | METHODS AND STRATEGIES
2.1 | Database and extraction
Web of Science (WOS) is an online citation database cover-
ing the fields of nature, humanities, and art in different
languages. Science Citation Index Expanded (SCI-E) is an
essential part of the WOS, including more than 9000
authoritative periodicals, which is updated every day.16
The papers were identified in this study from SCI-E.
The retrieval formula was “TS = (platelet-rich
plasma * OR PRP) AND TS = (wound * OR ulcer*)”.
English was selected as the paper language. The
retrieval time interval was from 2002 to 2021. The text
type with weak relevance, such as books, letters, meet-
ings, and so on was excluded. Figure 1 shows the flow
diagram of the retrieval process.
“Full Record and Cited References” record content
was exported in “Plain text” format, containing the title,
author names, abstract, keywords, references, and more
as the source of bibliometric analysis.
All Search Results were obtained within September
23, 2022, to avoid data inconsistencies caused by daily
database updates.
2.2 | Indicators and analysis process
We extracted indicators from SCI-E, including publication
number, citation frequency, published proportion,
H-index, and so on. The published proportion is calculated

LAI ET AL.
F I G U R E 1 Retrieval flow chart of
PRP in the treatment of wounds during
2002–2021
FIGURE 2 Publishing trends of the global and top three countries indexed by SCI-E
by dividing the number of publications per year by the
sum. The H-index is a mainstream measurement that aims
to evaluate the level of academic output and impact of the
research group. For example, an H-index of 63 means that
this researcher has published at least 63 papers that have
each been cited at least 63 times.
Through the built-in analysis function of WOS,
the results were obtained, including the publications of
different countries/regions, institutions, periodicals,
and authors about PRP in treating wounds. Microsoft
Excel was used to count and deal with. Combined with
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3
VOSviewer, the text data exported by WOS are integrated
with keywords, and then imported into SCImago
Graphica to generate the co-authorship geographic map.
Text data was imported into CiteSpace, set the
research time-slicing from 2001 to 2021, cut to 1 year,
selected the “Reference” and “Keyword” as analysis
nodes. The parameters were adjusted in accordance with
specific conditions, which could be seen in the figures.
Citespace visualisation consists of nodes of elements
such as references and keywords in datasets, the links
between nodes representing relationships of co-citations.
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4 LAI ET AL.

F I G U R E 3 Publishing country analysis. A, The number of publication, H-index (5), sum of citation (0.05), and average cited (4) of
the top 10 prolific countries. B, Co-authorship geographic map of different countries. Description of Figure 3B: 1: the United States; 2: China;
3: Italy; 4: Spain; 5: India; 6: Japan; 7: Turkey; 8: Germany; 9: Brazil; 10: France; 11: England; 12: Iran; 13: Egypt; 14: South Korea; 15:
Switzerland; 16: Canada; 17: Australia; 18: Netherlands; 19: Poland; 20: Russia; 21: Indonesia; 22: Belgium; 23: Saudi Arabia; 24: Austria; 25:
Portugal; 26: Sweden; 27: Chile; 28: Singapore; 29: Hungary; 30: Thailand

The colour of the links between the nodes means the year
in which they were first co-citations. The size of the circle
indicates the number of times the information is refer-
enced. The colour of Tree Ring History represents the
time of a corresponding citation. The purple outer ring
may be the critical information in the field.17,18
3 | RESULTS
3.1 | Trends in global publications
A total of 1748 studies were identified in the SCI-E
from 2002 to 2021 (Figure 1). According to the WOS
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LAI ET AL. 5

F I G U R E 4 Publishing institutions and journals analysis. A, Top 10 institutions related to PRP in the treatment of wounds
research. B, The number of publication and 5-year impact factor of the top 10 scholarly journal

classification, the main categories were presented Since 2002, the number of publications on PRP in the
as follows: surgery (355), dermatology (267), cell biol- treatment of wounds has shown an increasing trend, from
ogy (190), medicine Research Experimental (186), 6 (in 2002) to 228 (in 2021) (Figure 2). The United States,
and so on. China, and Italy, as the top 3 countries, published
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6 LAI ET AL.

TABLE 1 The information of the top 10 retrieved papers sorted by citation frequency.

Corresponding Total
Title author Year Journal citations PMID
Autologous platelets as a source of proteins for healing Alan T Nurden 2004 Thromb. Haemost. 965 14 691 563
and tissue regeneration
Platelet quantification and growth factor analysis from Barry L. Eppley 2004 Plast. Reconstr. Surg. 703 15 509 939
platelet-rich plasma: Implications for wound healing
Fibrin: A versatile scaffold for tissue engineering Max Hincke 2008 Tissue Eng. Part B-Rev. 631 18 544 016
applications
Platelets, inflammation and tissue regeneration Alan T. Nurden 2011 Thromb. Haemost. 511 21 479 340
Advancing biomaterials of human origin for tissue Fa-Ming Chen 2016 Prog. Polym. Sci. 509 27 022 202
engineering
Toward delivery of multiple growth factors in tissue Fa-Ming Chen 2010 Biomaterials 474 20 493 521
engineering
Strategies for controlled delivery of growth factors and Antonios G. Mikos 2012 Adv. Drug Deliv. Rev. 432 22 342 771
cells for bone regeneration
New insights into and novel applications for platelet- Isabel Andı´a 2006 Trends Biotechnol. 349 16 540 193
rich fibrin therapies
Platelets and wound healing Alan T Nurden 2008 Front. Biosci. 345 18 508 453
Platelet-rich plasma: A review of Biology and Barry L. Eppley 2006 Plast. Reconstr. Surg. 323 17 051 095
applications in plastic surgery

835 papers on this subject, accounting for 47.8% of the
total. The United States has always been leading in the
retrieval cycle. After 2016, The United States stabilised at
26–36 papers per year. China published the first paper in
2006, increasing with each passing year. China success-
fully surpassed the United States in 2019 and published
37 articles. For comparison, the number of publications in
Italy was more stable than in the United States and China,
but Italy reached 31 in 2020.
greatest total co-authorship link strength are shown in
Figure 3B. Colour depth and line weight represent the
strength of association between various countries/
regions of the research theme. The top 5 countries with
the largest total link strength were as follows: the
United States (total link strength = 183), China (102),
Switzerland (86), Italy (84), and France (78). More spe-
cifically, the size of digital labels is also the sort of the
number of publications.

3.2 | Contribution and association of 3.3 | Analysis of institutions, journals,

countries/regions papers

The United States, China, and Italy published 373, 241,
and 221, respectively, followed by Spain (128), India
(90), Turkey (85), Japan (85), Germany (72), Brazil (70),
and France (59). The papers published of the
United States have led in times cited (14637) and
H-index (63). Though Italy was slightly lower than
China in the number of publications, the H-index and
average cited (47, 28.45) were higher than that in China
(38, 27.01). In addition, France had no advantage in
publication but ranked 5th (32) in H-index and 1st
(85.69) in average cited. The details about H-index,
times cited, and average cited of the top 10 countries are
shown in Figure 3A.
There are 80 countries focusing on the topic of PRP
in the treatment of wounds, 30 countries with the
In terms of leading publishing institutions, Harvard
University published the most, with 49 studies. Boston
Children's Hospital (32), University of Rome Tor
Vergata (23), University of Bern (23), University of the
Basque Country (22), Tehran University of Medical Sci-
ences (22), University of London (20), Southern Medical
University (17), and Shanghai Jiao Tong University
(17) were as followed. Among them, there are two insti-
tutions from the United States and China, respectively.
One each from Egypt, Italy, Switzerland, Spain, Iran,
and England (Figure 4A).
Accounted for 13.7% papers within our observed
scope were published in the top 10 journals (240). There
were 35 studies in Wound Repair and Regeneration
(5-Year IF = 4.213), 30 studies in International Journal of
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LAI ET AL. 7

F I G U R E 5 Keywords analysis of PRP in the treatment of wounds. A, Co-occurrence map of keywords. B, Top 15 keywords with the
strongest citation bursts

F I G U R E 6 Co-citation and cluster analysis of references to PRP therapy for wounds. A, Co-citation map of references. B, Cluster
map of references

Molecular Sciences (6.628), and 29 studies in Journal of
Periodontology (5.277). The details of the top 10 journals
with the most publications are shown in Figure 4B.
We listed the top 10 papers with the most citation fre-
quency. For instance, a study entitled “Autologous platelets
as a source of proteins for healing and tissue regeneration”
by Alan T Nurden et al ranked first (Total citations = 965
times) since published in 2004. The information of these
papers, including article title, corresponding author, publi-
cation year, journal, total citations, and PMID (PubMed
Unique Identifier) are summarised in Table 1.
3.4 | Co-occurrence and burst detection
of keywords
Undoubtedly, the “PRP” was a keyword with the most
referred (1332 times) and highest centrality (0.86). The
followed was “growth factor” (841 times, Central-
ity = 0.50), “wound healing” (542 times, 0.24), “stem
cell” (333 times, 0.21), “gel” (300 times, 0.67), “regenera-
tive medicine” (296 times, 0.51), “in vitro” (218 times,
0.42), “fibrin” (201 times, 0.34), “randomized controlled
trial” (176 times, 0.30), “tissue engineering” (176 times,
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8 LAI ET AL.

TABLE 2 The information of the top 10 references sorted by co-citation frequency.

Corresponding Cited
Title author Year Journal frequency Centrality Degree PMID
Autologous platelet-rich Maria José Martinez- 2016 Cochrane 67 0.11 3 27 223 580
plasma for treating Zapata Database
chronic wounds Syst Rev.
Platelet-Rich Plasma for the Sherif A. Reffat 2017 Ann. Vasc. 54 0.44 11 27 522 981
Treatment of Clean Surg.
Diabetic Foot Ulcers
Classification of platelet Dohan Ehrenfest 2009 Trends 46 0.03 2 19 187 989
concentrates: from pure Biotechnol.
platelet-rich plasma (P-
PRP) to leucocyte- and
platelet-rich fibrin (L-
PRF)
Platelet-rich plasma: Alan Dardik 2010 Yale J. Biol. 44 0.69 4 20 351 977
support for its use in Med.
wound healing
Treatment of chronic non- Venkatesh Ponemone 2017 J. Biomed. 44 0.03 2 28 241 824
healing ulcers using Sci.
autologous platelet-rich
plasma: a case series
Platelet-rich plasma: Robert E. Marx 2004 Oral 43 0.09 4 15 085 519
evidence to support its Maxillofac.
use Surg
Comparative release of Richard J. Miron 2016 Clin. Oral 36 0.07 2 26 809 431
growth factors from PRP, Investig.
PRF, and advanced-PRF
Platelet-rich plasma Paola Romina Amable 2013 Stem Cell 35 0.85 4 23 759 113
preparation for Res. Ther.
regenerative medicine:
optimization and
quantification of
cytokines and growth
factors
Platelet quantification and Barry L. Eppley 2004 Plast. 35 0.12 1 15 509 939
growth factor analysis Reconstr.
from platelet-rich plasma: Surg.
implications for wound
healing
The growing evidence for Picard Frédéric; 2015 Wound 34 0.03 3 26 019 054
the use of platelet-rich Repair
plasma on diabetic Regen.
chronic wounds: A
review and a proposal for
a new standard care

0.04), and so on. And the co-occurrence relationship
between different keywords is shown in Figure 5A.
We set the minimum burst duration was 2-year,
then viewed and selected the top 15 keywords with the
strongest citation bursts (Figure 5B). The red line rep-
resents the period of the burst words, prompting the
beginning and end of the time interval of each burst.
The strongest keyword was “fibrin” (strength = 13.07),
followed by “enhance” (9.93) and “growth factor”
(8.14). The keyword with the longest burst duration
was “thrombin” (began in 2002 and ended in 2014).
Lately, “diabetic foot,” “pressure ulcer,” and “skin
regeneration” would be continuous burst keywords in
the next period.

LAI ET AL.
3.5 | Co-citation and cluster analysis of
references
Co-citation network map of cited references was created
by CiteSpace, and 342 nodes and 635 links are placed
(Figure 6A). The gradual change of colour represents
scale of the time. We showed the papers with high cita-
tions and strong clustering as much as possible. The arti-
cle entitled “Autologous platelet-rich plasma for treating
chronic wounds” published by Martinez-Zapata MJ et al
in 2016 was cited the most times in the identified studies
(Cited frequency = 67, Centrality = 0.11, Degree = 3).
Moreover, The detail of the top 10 references ranked by
co-cited frequency, centrality, and burst are summarised
in Table 2, which includes title, corresponding author,
publication year, journal, cited frequency, centrality,
degree, and PMID.
Meanwhile, Log-Likelihood Ratio (LLR) was used to
label clusters of the references. The major 10 clusters are
shown in Figure 6B. As a result, the largest 10 co-citation
clusters are as follows: endothelial cell proliferation (#0),
regenerative medicine-associated treatment (#1), diabetic
wound healing (#2), autologous derived (#3), platelet-
rich fibrin (#4), tissue engineering (#5), regenerative
potential (#6), clinical randomised trial (#7), histologic
observation (#8), and wound bacteria (#9).
4 | DISCUSSION
From 2002 to 2021, the number of publications in the
treatment of wounds with PRP generally increased
year by year. As of the date of retrieval, we also
searched for 144 papers in 2022, considered for incom-
plete coverage. Additionally, due to the lag of collec-
tion and update of some publications and networks,
we would make a prediction: PRP therapy for wound
healing will be a hot topic for relevant researchers in
scientific research and more academic studies will be
output in the future.
The United States and China ranked first and second
for the number of publications and the sum of citations,
respectively. It indicated that scientists from the
United States and China have published several high-
level papers in this area of research and were in a leading
position in the world. Notably, we found that China did
not publish its first relevant paper until 2006, but the
number of publications in 2019 (37) surpassed that of
the United States (31) for the first time. The rapid
increase in the China publication rate was closely related
to the medical and academic investment supported by
the government.19 Italy also has an excellent scientific
research foundation for PRP treatment of wounds, which
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9
benefits from the minor and stable changes in the num-
ber of publications. At the same time, Italy was higher
than China in H-index, which is reflected academic
impact (47 vs. 38). The number of publications in Spain
and France was significantly lower than that in China
and Italy, but the H-index was close to that in China
(36 and 32 vs. 38), and the average cited was higher than
that in the latter (43.75, 85.69 vs. 27.01), especially in
France (Ranked first in H-index). It demonstrated that
the relationship between research influence and the
number of publications is not a simple linear one. With
this result, every country or region would need to rein-
force academic management further.
The co-authorship among countries in PRP ther-
apy for wounds was relatively close, mainly by the
United States (Radiation links), European countries
(Centralised links), and East Asia (China, Japan, and
Korea). Likewise, a similar rule appeared in the contribu-
tion of institutions. Institutions from the United States still
had a decisive advantage in the number of publications,
followed by China. The distribution of other countries'
institutions in publication was relatively uniform.
Research publications cover various fields, including
basic and clinical medicine, nursing care, and bioengi-
neering. The top 10 journals focus on wound repair and
tissue engineering. The future development of PRP in
wound therapy may be published in those journals
shown in Figure 4B.
Published papers with high citation frequency are
considered to have a marvellous impact on the academic
frontier. We found that Alan T Nurden et al had excellent
academic output on this topic, taking three of the top
10 places (ranked first, 965 times; ranked fourth,
511 times; ranked ninth, 345 times). They have compre-
hensively explored the field of platelets and their prod-
ucts in the treatment of wounds, covering the review of
mechanisms, experiments, and clinical application. It
was worth noting that Alan T Nurden's team has devel-
oped many new scientific directions around platelets.
Until 2022, the team will still have high-quality achieve-
ments published in high-level journals. Posteriorly, the
paper entitled “Platelet quantification and growth factor
analysis from platelet-rich plasma: Implications for
wound healing” has been cited for 703 times since its
publication, which was ranked second in the related
field. This study was published on Plastic and Reconstruc-
tive Surgery in 2004, whose corresponding author was
Barry L. Eppley. They demonstrated that the concentra-
tion of platelet-rich plasma was positively correlated with
the level of growth factor, which could potentially help
wound repair.20 The detailed information of the top
10 publications about PRP in wound healing applications
is listed in Table 1.

10
From the analysis of the major co-occurrence key-
words and the exploration of the strongest citation burst
keywords, we found that researchers focused more on
the wound repair effect of growth factors and clinical
practices. A study has shown that combining PRP and
adipose-derived stem cells (ASCs) could accelerate dia-
betic wound healing induced experimentally in mice.21
The construction of related animal models was an impor-
tant bridge connecting mechanism research and random-
ised controlled trial. In addition, some multi-dimensional
concepts (such as “tissue engineering” and “regenerative
medicine”) and specific disease (such as “diabetic foot”
and “pressure ulcer”) reflected that PRP therapy has
become more and more professional. Due to evidence-
based medicine, future researches on PRP therapy for
wounds should be more scientific.
Co-citation and cluster analysis on references, which are
helpful to clarify the development process and research hot-
spots in this field.17,18 Therefore, we inferred the hotspots of
PRP for wound treatment and listed them as follows.
4.1 | Mechanism of growth factors in
PRP promoting wound healing
Activated PRP could produce different growth factors,
including vascular endothelial growth factor (VEGF),
transforming growth factor (TGF), insulin-like growth
factor (IGF), and other repair-related.22,23 However, the
specific mechanism of the growth factors in PRP syner-
gistically promoting wound healing remains unclear.
4.2 | PRP combination therapy
Suthar M et al have treated chronic wounds by autoge-
nous PRP subcutaneous injection. New granulation tissue
and shrinks were seen in the wound basement for
4 weeks.24,25 The application of PRP combined with other
therapeutic techniques, such as negative pressure wound
therapy (NPWT), ASCs transplantation, and genetic engi-
neering biotechnology, would further improve the thera-
peutic effect of wounds.26-28
4.3 | Preparation of PRP
Although the preparation techniques of PRP improved over
the years, a standardised method has been lacking. It
seemed unreasonable to assume that platelet count posi-
tively correlated with growth factor concentration. Zimmer-
mann R et al pointed out that changes in growth factor
concentration may be related to the contamination of white
blood cells.29 Therefore, conditions (preparation
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LAI ET AL.
temperature, time, etc.) would affect the total amount of
growth factors and decide the treatment effect of PRP
on wound treatment. Furthermore, Anitua E found no
dose–response relationship between platelet concentra-
tion and expression of fibrocyte collagen (COL).30 Thus,
there is no consensus on the optimal concentration of
PRP for wound treatment.
4.4 | More clinical trials
High-quality randomised controlled clinical trials are consid-
ered the gold standard of clinical evidence. Many researchers
have done substantial work on PRP therapy for wounds.
However, these studies with small sample sizes and scattered
were not fully accepted.14,23,31 More multi-center and rigor-
ous randomised controlled trials are needed to be further
studied, which can avoid the bias caused by subjective fac-
tors of subjects and researchers. But the disadvantage is that
the method is complicated to implement. The feasibility of
this method should be carefully considered in the early
stage.
5 | CONCLUSION
In our study, the research theme on PRP in the treatment
of wounds was dissected comprehensively. The
United States has made the most outstanding contribution
in this field. Although China has a sizable number of pub-
lications, the quality of some of these papers may need to
be improved. The latest research progress could be
searched in Wound Repair Regen., Int. J. Mol. Sci. and
J. Periodont. Alan T Nurden, Barry L. Eppley, and Fa-
Ming Chen are prominent researchers in the area. The
mechanism of growth factors of PRP, combination ther-
apy, preparation of PRP, and related clinical trials may be
topics that need attention.
A C KN O WL ED G EME N T S
We acknowledge WOS database for providing their plat-
forms and contributors for uploading their meaningful
datasets. Thanks for the Citespace provided by Professor
Chen Chaomei, which is very helpful for the analysis of
our study results.
F U N D I N G IN F O R M A T I O N
This work was funded by the National Natural Science
Foundation of China (81901960) and the foundation of
Shanghai hospital development center (SHDC2020CR4100).
CONFLICT OF INTEREST
No potential conflict of interest was reported by the
authors. These data are downloaded from the public

LAI ET AL.
database as reference data and do not involve any animal
experiments or human experiments. So there are no ethi-
cal issues with these data.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are openly
available in Web of Science (https://access.clarivate.com/).
ORCID
Honghao Lai https://orcid.org/0000-0003-1882-2208
Guangping Chen https://orcid.org/0000-0002-8316-
9033
Wei Zhang https://orcid.org/0000-0001-5760-1710
Guosheng Wu https://orcid.org/0000-0002-4612-9059
Zhaofan Xia https://orcid.org/0000-0002-8192-2693
R EF E RE N C E S
1. Tottoli EM, Dorati R, Genta I, Chiesa E, Pisani S, Conti B. Skin
wound healing process and new emerging technologies for skin
wound care and regeneration. Pharmaceutics. 2020;12(8):735.
2. Morton LM, Phillips TJ. Wound healing and treating wounds:
differential diagnosis and evaluation of chronic wounds. J Am
Acad Dermatol. 2016;74(4):589–606.
3. Arnold M, Barbul A. Nutrition and wound healing. Plast
Reconstr Surg. 2006;117(7 Suppl):42 S-58 S.
4. Broadbent E, Koschwanez HE. The psychology of wound heal-
ing. Curr Opin Psychiatry. 2012;25(2):135-140.
5. Catanzano O, Quaglia F, Boateng JS. Wound dressings as
growth factor delivery platforms for chronic wound healing.
Expert Opin Drug Deliv. 2021;18(6):737-759.
6. Etulain J. Platelets in wound healing and regenerative medi-
cine. Platelets. 2018;29(6):556-568.
7. Fang J, Wang X, Jiang W, et al. Platelet-rich plasma therapy in
the treatment of diseases associated with orthopedic injuries.
Tissue Eng Part B Rev. 2020;26(6):571-585.
8. Zhang S, Li P, Yuan Z, Tan J. Platelet-rich plasma improves thera-
peutic effects of menstrual blood-derived stromal cells in rat model
of intrauterine adhesion. Stem Cell Res Ther. 2019;10(1):61.
9. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR,
Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor
enhancement for bone grafts. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod. 1998;85(6):638-646.
10. Whitman DH, Berry RL, Green DM. Platelet gel: an autologous
alternative to fibrin glue with applications in oral and maxillo-
facial surgery. J Oral Maxillofac Surg. 1997;55(11):1294-1299.
11. Kim SA, Ryu HW, Lee KS, et al. Application of platelet-rich
plasma accelerates the wound healing process in acute and
chronic ulcers through rapid migration and upregulation of cyclin
A and CDK4 in HaCaT cells. Mol Med Rep. 2013;7(2):476-480.
12. Soliman AF, Saif-Elnasr M, Abdel FS. Platelet-rich plasma ame-
liorates gamma radiation-induced nephrotoxicity via modulating
oxidative stress and apoptosis. Life Sci. 2019;219:238-247.
13. Evans CE, Humphries J, Waltham M, et al. Protein fragments
from the VEGF binding domain of fibronectin are expressed in
distinct spatial and temporal patterns during venous thrombus
resolution. Thromb Res. 2012;130(2):281-284.
14. Everts PA, Devilee RJ, Brown MC, et al. Exogenous application of
platelet-leukocyte gel during open subacromial decompression
1742481x, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iwj.14047 by National Medical Library The Director, Wiley Online Library on [12/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
11
contributes to improved patient outcome. A prospective random-
ized double-blind study. Eur Surg Res. 2008;40(2):203-210.
15. Menchisheva Y, Mirzakulova U, Yui R. Use of platelet-rich plasma
to facilitate wound healing. Int Wound J. 2019;16(2):343-353.
16. Birkle C, Pendlebury DA, Schnell J, Adams J. Web of science
as a data source for research on scientific and scholarly activity.
Quant Sci Stud. 2020;1(1):363-376.
17. Chen C, Song M. Visualizing a field of research: a methodology of
systematic scientometric reviews. PLoS One. 2019;14(10):e223994.
18. Chen C. CiteSpace: A Practical Guide for Mapping Scientific Lit-
erature. Hauppauge, NY: Nova Science Publishers Inc; 2016.
19. Li X, Krumholz HM, Yip W, et al. Quality of primary health
care in China: challenges and recommendations. Lancet. 2020;
395(10239):1802-1812.
20. Anitua E, Andia I, Ardanza B, Nurden P, Nurden A. Autolo-
gous platelets as a source of proteins for healing and tissue
regeneration. Thromb Haemost. 2004;91(1):4-15.
21. Ebrahim N, Dessouky AA, Mostafa O, et al. Adipose mesenchy-
mal stem cells combined with platelet-rich plasma accelerate
diabetic wound healing by modulating the Notch pathway.
Stem Cell Res Ther. 2021;12(1):392.
22. Escamilla CM, Domínguez-Maldonado G, Cordoba-Fernandez A.
Efficacy and safety of the use of platelet-rich plasma to manage
venous ulcers. J Tissue Viability. 2017;26(2):138-143.
23. Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of platelet-rich
plasma in the treatment of knee osteoarthritis: a meta-analysis
of randomized controlled trials. Art Ther. 2017;33(3):659-670.
24. Suthar M, Gupta S, Bukhari S, Ponemone V. Treatment of
chronic non-healing ulcers using autologous platelet rich
plasma: a case series. J Biomed Sci. 2017;24(1):16.
25. Babaei V, Afradi H, Gohardani HZ, Nasseri F, Azarafza M,
Teimourian S. Management of chronic diabetic foot ulcers
using platelet-rich plasma. J Wound Care. 2017;26(12):784-787.
26. Sessions JW, Armstrong DG, Hope S, Jensen BD. A review of
genetic engineering biotechnologies for enhanced chronic
wound healing. Exp Dermatol. 2017;26(2):179-185.
27. Yusuf E, Jordan X, Clauss M, Borens O, Mäder M, Trampuz A.
High bacterial load in negative pressure wound therapy
(NPWT) foams used in the treatment of chronic wounds.
Wound Repair Regen. 2013;21(5):677-681.
28. Arezoumand KS, Alizadeh E, Esmaeillou M, et al. The emu oil
emulsified in egg lecithin and butylated hydroxytoluene
enhanced the proliferation, stemness gene expression, and
in vitro wound healing of adipose-derived stem cells. In Vitro
Cell Dev Biol Anim. 2018;54(3):205-216.
29. Zimmermann R, Jakubietz R, Jakubietz M, et al. Different prepara-
tion methods to obtain platelet components as a source of growth
factors for local application. Transfusion. 2001;41(10):1217-1224.
30. Anitua E, Sanchez M, Zalduendo MM, et al. Fibroblastic
response to treatment with different preparations rich in
growth factors. Cell Prolif. 2009;42(2):162-170.
How to cite this article: Lai H, Chen G,
Zhang W, Wu G, Xia Z. Research trends on
platelet-rich plasma in the treatment of wounds
during 2002–2021: A 20-year bibliometric analysis.
Int Wound J. 2022;1‐11. doi:10.1111/iwj.14047