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. 2022 Oct 23;20(5):1725–1738. doi: 10.1111/iwj.13988

Global research status of pathological scar reported over the period 2001–2021: A 20‐year bibliometric analysis

Shiyi Li 1, Hongfan Ding 1, Yi Yang 1, Boya Yu 1, Minliang Chen 1,✉
PMCID: PMC10088839  PMID: 36274191

Abstract

Pathological scar is a classic problem in plastic and reconstructive surgery. Although the researches on pathological scar have been conducted for decades, the way to go to address this thorny problem still remains challenging. To the best of our knowledge, few bibliometric analysis concerning pathological scar have been reported. In this study, we set out to employ bibliometric and visual analysis to offer research status and trends of pathological scar over the period 2001–2021. All publications covering pathological scar during 2001–2021 were retrieved and extracted from the Web of Science database. We applied VOSviewer software to evaluate the keywords and research hotpots, and the online tool (http://bibliometric.com/) was used to carried out the publication trends analysis. A total of 2221 pathological scar‐related articles were identified over the period 2001–2021. China is the country which had the largest volume of publications (819, 36.87%), followed by the United States (416, 18.73%), Japan (144, 6.48%), Korea (142, 6.39%), and England (118, 5.31%). Among the institutions and journals, Shanghai Jiao Tong University (167) and Wound Repair and Regeneration (85) accounted for the most papers related to pathological scar, respectively. Professor Bayat A, who had the most citation frequency (2303), made great contribution in pathological scar field. “Fibroblast”, “expression”, and “proliferation” were identified as the pathological scar research hotspot through analysis of the keywords. In terms of publication, China ranked first all over the world, but the numbers of publication are inconsistent with the citation frequency, ranking first and second, respectively. Shanghai Jiao Tong University and journal Wound Repair and Regeneration stand for the highest level of research in this field to a certain extent. In the early stage, the research focus was mainly on the prevention, treatment, and risk factors for recurrence of pathological scar from cases. In the later stage, the research focus was on the comprehensive management, in which the mechanism research was in‐depth to the molecular and gene level.

Keywords: bibliometric analysis, hypertrophic scar, keloid, keywords, pathological scar, research hotspots

1. INTRODUCTION

Keloid and hypertrophic scar are referred to pathological scar, which is a fibrous metabolic disease characterised by excessive fibrosis and collagen deposition in human dermis. 1 In the process of wound healing, the disorder of cell structure and function results in excessive dermal fibrosis, which is distinguished by an overgrowth of the dense fibrous tissues that form around or beyond the original wound. 2 It's reported that about 100 million scars developed yearly, among them 11 million would become keloids. 3 In addition to morphologic alteration, it can also cause itching and pain, which have a miserable impact for patients' lives. 4 In spite of the rapid development of biotechnology and the increasing research on scarring, its pathogenesis is still not fully elucidated and, therefore, no definitely effective treatment is available. 5 Dysfunction of fibroblasts and keratinocytes, inflammatory response of reticular dermis, abnormal expression of fibrosis signalling pathways, and genetic susceptibility are all involved. 6 , 7 , 8 The research on pathological scar is still a major problem and hotspot in medical research globally. TGF‐β1/Smad signalling pathway, MAPK pathway, integrin pathway, mTOR pathway, Wnt/β‐catenin pathway, and oxidative stress‐related pathways are all considered to have a close relationship with pathological scar. Researchers believe that the occurrence and progression of pathological scar are regulated by the interaction of multiple signalling pathways. 7 , 9 , 10 , 11 , 12

There are several traditional treatment strategies for scar, including surgery (expander implantation, scar excision, etc.), non‐surgical treatment, and comprehensive treatment. Scar excision is not suitable for all patients, and the postoperative scar recurrence rate is also high. It is estimated that about 70% recurrence rate at the excision site after. 13 Non‐surgical methods include drug injection, pressure therapy, chemotherapy, cryotherapy, etc. However, the traditional non‐surgical treatment can only alleviate symptoms with mixed results. 14 In recent years, the photoelectric technology and mesenchymal stem cell therapy have been favoured by clinicians. 15 , 16 However, it is a pity that no single therapy has achieved satisfactory efficacy so far. Therefore, new treatment methods are still being explored. 14

Bibliometrics regarded as the gold standard for evaluating activity in a research field, which not only enables comparison of contributions from different countries, institutions, journals, and scholars, but also describes a specific area of research and predicts concrete trends and future research focuses. 17 In the field of pathological scar, few bibliometric studies have been performed, which implies a lack of systematic pathological scar analysis and prediction of research hotspots. The objective of our study was to analyse the researches on pathological scar published from 2001 to 2021, identify the current research hotspots and bottlenecks, and summarise the breakthroughs and achievements made in recent years, so as to better provide guidance for the follow‐up clinical and scientific research work.

2. MATERIALS AND METHODS

2.1. Data sources and search strategies

A comprehensive online search was conducted from 2001 to 2021 applying WOS database with literature types limited to original articles and reviews. The search strategy was as follows: TI = (hypertrophic scar) OR TI = (hypertrophic scars) OR TI = (cicatrix) OR TI = (hypertrophic cicatrix) OR TI = (keloid) OR TI = (pathological scar) AND Language = English. Two authors (LSY and YY) of this paper independently removed repetition from the retrieved literatures. If there is any inconsistency in the removal, the corresponding author of this paper will make the ultimate decision on relevant issues after discussion. Literature retrieval and data collecting were accomplished within one day on 12 April 2022 to avoid the database updates. The details of the process of the literature inclusion and exclusion was presented in Figure 1.

FIGURE 1.

FIGURE 1

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Flow diagram of literature selection and screening in this study

2.2. Data collection

Two reviewers (LSY and DHF) independently extracted characteristics data from all included publications, including titles, keywords, publication dates, countries and regions, authors, institutions, publishing journals, sum of citations, H‐index. The online tool of bibliometrics (http://bibliometric.com/) was used for qualitative and quantitative analyses.

2.3. Bibliometric analysis

All characteristics of eligible publication documents in WOS were recorded in detail. H‐index value, also known as h‐factor, which can be used to evaluate the quantity and level of academic output of researchers. In this study, we made a comparative analysis of annual publications and publication growth trends among different countries/regions with high academic output. The keyword network extracted from pathological scar research was visualised by applying VOSviewer software and the keywords were classified into different clusters based on cooccurrence analysis at the same time. Besides, we coloured the keyword in accordance with its time of appearance, for which we introduced the concept of average year of occurrence (AAY) to better evaluate the novelty of the keywords and research hotspots.

3. RESULTS

3.1. Global growth trends of publications

Our search identified a total of 2221 articles according to the inclusion criteria. The global trend of publications on pathological scar research was showed in Figure 2. It is noticeable that the overall number of publications tends to increase significantly with the year. The year 2021 (228, 8.92%) was the year with the highest volume of pathological scar‐related publications.

FIGURE 2.

FIGURE 2

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The number of annual publications in pathological scar from 2001 to 2021

China, the United States, and Japan were the top three countries that published the highest volume of papers, being selected to describe and compare their publication trends. The curves show that China's growth trend is consistent with that of the world. The curve of annual publication in China was relatively flat before 2010, but after 2010, the growth rate increased significantly, while the United States and Japan have maintained a stable and relatively flat growth trend. (Figure 3).

FIGURE 3.

FIGURE 3

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The curves of growth trends of publications related to pathological scar (A) Global; (B) China; (C) the United States; (D) Japan

3.2. Contribution of countries to global publications

China ranked first in terms of the number of publications (819, 36.87%), followed by the United States (416, 18.73%), Japan (144 6.48%), Korea (142, 6.39%), and England (118, 5.31%). Meanwhile, we turned our eyesight to the relationship between the number of literature published in a country/region over the time course. The results also showed that the European countries and America were predominantly published from 2001 to 2011. In the recent five years, the Asian countries (China, Japan, South Korea, etc.) published a large number of hypertrophic scar‐related literature, becoming the leading countries and regions that published hypertrophic scar‐related literature. The details of the data of the top 10 countries/regions regarding the number of publications can be seen in Figure 4A.

FIGURE 4.

FIGURE 4

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The contributions of different countries/regions to the research field concerning pathological scar. (A) The growth trends of the top 10 countries/regions in pathological scar during 2001–2021. (B) The number of publications, citation frequency (×0.05), and H‐index (×10) of the top 10 countries or regions

The results of the cited frequency of included articles suggested that the 2221 articles related to pathological scar were cited 50 457 times since 2001 (30 614 times without self‐citation). The average citation frequency was 22.72 times per literature, and the H‐index was 94. Figure 4B summarized the data on the contributions of the top 10 countries/regions to the research field on the pathological scar. The citation frequency of the United States (14 461 times, 14 043 times without self‐citation) is the highest, accounting for 22.71% of the total. The average citation per literature was 34.76 times, with an H‐index of 62. The annual publication volume of the United States increased yearly, and the growth rate was constant. Publications in China were cited 10 687 times (8165 times without self‐citation), with an H‐index of 45, ranking second globally. In addition, before 2016, the publication volume of the United States is more than that of China per year. Since 2016, China's annual publication number surpassed the United States for the first time and has maintained its lead ever since. Although China's publication volume has surpassed the United States and the growth rate shows an obvious trend of increase, its citation frequency was fewer than the United States, which means that the quality of the articles from China may not be as good as the US in this area.

To provide an in‐depth understanding of the level of cooperation between countries/regions around the world, we used the VOS Viewer to create a map of cooperation between countries/regions. China and the United States are the two major countries with the largest volume of publications, and both countries have carried out extensive international cooperation. Given that the total number of national publications, the proportion of international cooperation in the number of publications in the United States is significantly higher than that in China, which can be seen as the central position among the cooccurrence network of China and the United States (Figure 5).

FIGURE 5.

FIGURE 5

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The cooperation of countries/regions in pathological scar research during 2001–2021

3.3. Contribution of institutions to global research on pathological scar

Shanghai Jiao Tong University was the institution which published the highest number of pathological scar‐related manuscripts in the past twenty years all over the world (167, 7.5%). Among the top10 institutions in this field, four of them were from China. The other six were the University of Manchester in England, National University of Singapore, Yonsei University in Korea, the University of Alberta in Canada, Nippon Medical School in Japan, and Vrije University Amsterdam in Netherlands (Figure 6A). In addition, we also focused on the academic cooperative relationships among these major institutions in order to better assess their international academic status and influence in the field. Shanghai Jiao Tong University, Anhui Medical University from China, and National University of Singapore spotted at the centre of the cooperation nexus map, which indicated their extensive international cooperation. Meanwhile, it was necessary to analyse the publications of each major academic institution upon time course, which can reflect the research activity of the institution in this field. The results showed that most institutions published pathological scar‐related literature primarily before 2016, whereas the Shanghai Jiao Tong University published numerous papers in recent five years (Figures 6B,C).

FIGURE 6.

FIGURE 6

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The contributions and cooperation of different institutions. (A) Distribution of top 10 institutions focusing on pathological scar; (B) The cooperation of institutions in pathological scar, and the circle with a large size represented the institution that published more articles; (C) Distribution of institutions was presented according to the appearance for the average time

3.4. Journals and authors focus on pathological scar

The top 10 journals published a total of 585 articles concerning pathological scar, accounting for approximately one‐fourth (26.34%) of all publications. Wound Repair and Regeneration (85), Burns (82), Dermatologic Surgery (75), and Plastic And Reconstructive Surgery (72) ranked the top four, with related literature accounting for 14.14% of the overall publications (Figure 7). Not surprisingly, Plastic And Reconstructive Surgery has the highest citation frequency among all journals(1805), with an average of 25.07 citations per article, which means it is the most prominent journal in the field.

FIGURE 7.

FIGURE 7

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The top 10 journals publishing research on pathological scar

The top 10 most cited pathological scar‐related works were listed based on the citation frequency. The most cited article, which entitled “Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies”, published in MOLECULAR MEDICINE in 2011 by Jeschke MG et al. The total citations and average annual citations of this paper were as high as 770 and 70, respectively. (Table 1).

TABLE 1.

Top 10 high‐cited papers related to hypertrophic scar

Article title Reprint addresses Journal IF Publication year Times cited Average per year
Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies Jeschke, MG MOL MED 6.354 2011 770 70
Hypertrophic Scars and Keloids‐A Review of Their Pathophysiology, Risk Factors, and Therapeutic Management Wolfram, D DERMATOL SURG 3.398 2009 401 30.84615385
Keloid pathogenesis and treatment Davison, SP PLAST RECONSTR SURG 4.763 2006 391 24.4375
Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis Gurtner, GC FASEB J 5.192 2007 336 22.4
Quality of life of patients with keloid and hypertrophic scarring Bock, O ARCH DERMATOL RES 3.017 2006 306 19.125
Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis Ogawa, R INT J MOL SCI 5.924 2017 287 57.4
Potential cellular and molecular causes of hypertrophic scar formation Niessen, FB BURNS 2.744 2009 256 19.69230769
Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment Berman, B DERMATOL SURG 3.398 2017 243 48.6
Treatment response of keloidal and hypertrophic sternotomy scars ‐ Comparison among intralesional corticosteroid, 5‐fluorouracil, and 585‐nm flashlamp‐pumped pulsed‐dye laser treatments Fitzpatrick, RE ARCH DERMATOL NA 2002 229 11.45
Hypertrophic scarring: the greatest unmet challenge after burn injury Finnerty, CC LANCET 79.323 2016 236 39.33333333
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Abbreviations: IF, impact factor; NA, Not available.

A total of 368 articles were published by the top 10 productive authors, accounting for 16.6% of all pathological scar‐related literature. Ardeshir Bayat, ranking first in publications, citation frequency and H‐value, from the University of Manchester, published 59 hypertrophic scar‐related articles, which were cited 2303 times. Japanese professor Ogawa R published 52 articles on this field, ranking second. Chinese Professor Li Y and Professor Niessen FB from the Netherlands published 38 articles, both ranking third. As presented in Table 2, among the top10 most productive authors, five resided in China, and the rest of them came from England, Japan, Singapore, Netherlands, and Canada, respectively.

TABLE 2.

Top 10 authors with most publications in research scope of hypertrophic scar

Author Country Affiliation No. of publications No. of citations Average H‐index
Bayat A England Univ Manchester 59 2303 39.03 30
Ogawa R Japan Nippon Med Coll Hosp 52 1961 37.71 21
Li Y China Fourth Mil Med Univ 38 582 15.32 13
Niessen FB Netherlands Vrije Univ Amsterdam 38 1457 38.34 18
Hu DH China Fourth Mil Med Univ 36 704 19.56 15
Liu Y China Harbin Med Univ 35 674 19.26 13
Phan TT Singapore Natl Univ Singapore 34 1564 46 24
Tredget EE Canada Univ Alberta 27 1306 48.37 21
Zhang Z China Shanghai Jiao Tong Univ 25 424 16.96 10
Li J China Fourth Mil Med Univ 24 495 20.63 14
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3.5. Analysis of keywords and research hotspots on pathological scar

The keywords were extracted from the 2221 qualified publications and analysed cooccurrence using VOSviewer. As presented in Figure 8A, 187 keywords with more than 15 cooccurrences were applied to the network analysis, which produced four clusters: cluster 1 (mechanism‐related research, blue), cluster 2 (clinical research, red), cluster 3 (diagnostic research, green) and cluster 4 (gene‐related research, yellow). The size of each dot represented its corresponding keyword frequency appearing in the title and abstract. In cluster 1, main keywords were as follows: fibroblast (513 times), expression(478 times), proliferation (248 times), fibrosis (225 times), apoptosis (217 times), and activation (129 times). In cluster 2, relevant keywords were hypertrophic scar (993 times), keloid (989 times), management (243 times), prevention (178 times), therapy (143 times), and surgical excision (85 times). In cluster 3, the keywords of high‐frequency appearing were skin (248 times), collagen (208 times), tgf‐beta (155 times), and tissue (129 times). The only four keywords in the fourth cluster are disease (87 times), susceptibility (21 times), polymorphism (19 times), and genetic susceptibility (19 times), respectively. Table S1 shows the details of results of all 187 keywords. In Figure 8B, we coloured all keywords via VOSviewer in consistence with the time the word appeared, with the blue representing the keyword appearing relatively earlier and yellow for recent emergency. Before 2014, messeger‐rna (cluster 3, AAY 2009), metabolism (cluster 1, AAY 2010), induction (cluster 1, AAY 2010), electron‐beam irradiation (cluster 2, AAY 2011), and receptors (cluster 1, AAY 2011) were the major research topics. Besides, analysis of cluster 1 suggested “cancer”(AAY 2016), migration (AAY 2016), pathway (AAY 2016), akt (AAY 2016), and cell‐proliferation (AAY 2016) might be the current research hotspots in pathological scar field. In cluster 2 (clinical research), the latest hot word were “photothermolysis (AAY 2018)” and “pathophysiology (AAY 2018)”, which appeared 20 and 26 times, respectively. In cluster 3 (diagnostic science research), “inflammation (AAY 2017)”, “stem cell (AAY 2016)”, and “identification (AAY 2017)” were identified as the novel keywords, appearing 58, 43, and 42 times, respectively.

FIGURE 8.

FIGURE 8

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The analysis of keywords in publications of pathological scar. (A) Mapping of the keywords in the area of pathological scar. The words were divided into four cluster in accordance with different colours generated by default: cluster 1 (mechanism‐related research, blue), cluster 2 (clinical research, red), cluster 3 (diagnostic research, green), and cluster 4 (gene‐related research, yellow). The circle with a large size represented the keywords that appeared at a high frequency; (B) Distribution of keywords was presented according to the appearance for the average time. The blue colour represented early appearance and yellow colour recent appearance. Two keywords cooccurred if they both occurred on the same line in the corpus file. The smaller the distance between two keywords, the larger the number of cooccurrences of the keywords

4. DISCUSSION

Pathological scar has always been a major problem in the field of plastic surgery with a high incidence and recurrence rate. Research on pathological scar has been ongoing since the last century, but its precise pathogenesis is still unclear and prevention is challenging. Bibliometric analysis is a novel and effective method that give a clear insight into contributions from different countries, institutions, journals, and scholars in a research field. More importantly, it can help researchers learn about the current research status and research hotspots. In this study, we extracted pathological scar‐related research literature from WOS and conduct a systematic analysis of the current status quo of research on pathological scar over the past 20 years using a bibliometric approach.

4.1. Research trends in pathological scar

It could be clearly seen from the current study that in the field of clinical treatment and basic research related to pathological scar, China and the United States rank first and second, respectively, in the number of publications, but the total citation number and H‐index value are on the contrary. the United States has the highest total citation number and H‐index value.

China is the most populous country as well as the largest developing country. Every year, there are a large number of people suffering from burns, trauma, or undergoing invasive surgery, and a substantial part of these people will inflict scars because of various reasons. 18 Moreover, the clinical management status of pathological scars contracture remains unknown. 19 In addition, researches have also shown that Asians and Africans are more susceptible to pathological scars and hyperpigmentation than Caucasians. 18 , 20 Given the relatively high incidence of pathological scar in Asia, it is not surprising that three of the top five countries and seven of the top 10 institutions are from Asia.

The United States was one of the first countries to conduct relevant studies on the pathological scar, and made a great contribution to the field, which can be illustrated by the number of published articles, the highest frequency of citations, and the H‐index. Of note, China ranked first in total publications but second in cited frequency and H‐index. The imbalance between the quantity and quality of Chinese publications may be caused by the following reasons. First of all, the treatment of pathological scar lacks standardisation in China. In fact, pathological scar is empirically treated in many cases without enough evidence‐based medical support such as guidelines or consensus, resulting in mixed outcomes. Besides, in China, most of the early relevant studies were retrospective studies, lacking high‐quality multicentre randomised controlled trials (RCT), so it was difficult to offer more reliable evidence for clinical management.

As evidenced by curves of growth trends of publications, since 2010, the number of cumulative publications on pathological scar has increased rapidly globally, which reflected the increasing interest of researchers in this field all over the world. The annual growth rate has reached a relatively stable level in many countries, including the United States and Japan. However, the number of publications on this topic has continued to grow in China, and the growth rate is still increasing. Meanwhile, there are a number of influential conferences on pathological scar held in China every year. Among the top 10 institutions in the pathological scar field, China boasted four. The institution which published the most articles was Shanghai Jiao Tong University from China. All of these indicated that China is playing an increasingly important role and demonstrating its principal dominance in the field of pathological scar to some extent. However, the frequency of citations and H‐index, both quantitative indicators used to evaluate the quantity and level of academic output of researchers or countries, ranked second in China. Therefore, the quality and evidence level of papers on pathological scar research by Chinese researchers need to be further strengthened.

As to journals, Wound Repair and Regeneration, Burns, Dermatologic Surgery, Plastic and Reconstructive surgery are major journals publishing pathological scar‐related papers, far ahead of other journals, which suggest that some breakthroughs and hotspots of future advances in this field are likely to be published in these journals.

In terms of authors, Bayat A from England, Ogawa R from Japan, Li Y from China, and Niessen FB from the Netherlands published the most articles related to pathological scar. Professor Bayat A mainly explored the genetic susceptibility to scar and related physiopathologic mechanisms of extracellular matrix, fibroblast, growth factor in hypertrophic scar, participating in the compilation of several guidelines, and consensus on photoelectric technology in the treatment of hypertrophic scar. 15 , 21 , 22 Professor Ogawa R has made many clinical studies and improvements in the sequential treatment of hypertrophic scar, especially in scar surgical excision, radiotherapy, steroid injection, etc., and put forward “neurogenic inflammation hypothesis” into aetiology and pathology of pathological scars. 23 , 24 , 25 Professor Phan TT from the National University of Singapore ranked only seventh in total publications, but third in total citation frequency of his papers. He has carried out a large number of basic experiments on fibrosis signalling pathways, transforming growth factors and inflammatory factor in hypertrophic scar, and observed the inhibitory effect on hypertrophic scar by blocking the expression of related signalling pathways or growth factors, providing theoretical basis for targeted scar therapy. 26 , 27 , 28 Besides, the cooperation between different authors also matters for the deeper exploration of pathological scar. Further retrieval and analysis of articles published by authors with highly cited literature showed that there were cooperative relations to a certain extent among scholars in the compilation of relevant guidelines for clinical treatment of scar, but cooperation among scholars in fundamental experiments on the pathogenesis of scar is far from adequate. Extensive cooperation can gather greater advantages, which will directly affect the development and the hotspots in this field. Therefore, we call for more extensive international academic cooperation, which will undoubtedly be of great benefit to the understanding of the pathogenesis of pathological scar.

4.2. Research focuses on pathological scar

The information of the top10 most cited articles in the pathological scar field are presented in Table 1. The article “Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies” has been cited 770 times since publication, making it the most cited paper in the field of pathological scar. This study was published in MOLECULAR MEDICINE in 2011 by Gerd G Gauglitz and Marc G Jeschke. This research systematically reviewed the role of inflammatory response, fibrogenesis signalling pathways, and matrix remodelling in the pathogenesis of pathological scar, and summarised the existing and novel treatment strategies, which were of great significance to the later clinical work. 29

The second and third highly cited articles were published in DERMATOL SURG and PLAST RECONSTR SURG, respectively. The two papers focused on the pathogenesis of hypertrophic scar and keloid. 30 , 31 Davison SP indicated that epidermal‐mesenchymal interaction might play a key role in the pathogenesis of keloid, and further suggested combination therapy appears to be the most efficacious and safest keloid management option available. 31 It is the latest research trend to apply epithelial‐to‐mesenchymal transition to coordinate the complex pathway mechanism of keloid and to view the occurrence and development of keloid from a dynamic perspective. 32 , 33 TGF‐β is the most critical growth factor in keloid formation. Jeschke MG and Davison SP both mentioned that the use of recombinant human TGF‐β3, anti‐TGF‐β1 and anti‐TGF‐β2 may have unexpected therapeutic effects in the treatment of hypertrophic scar, but the exact efficacy and specific mechanisms need further verification in future. 29 , 31 In actual fact, the majority of the top 10 cited papers were on the pathogenesis and pathophysiological process of hypertrophic scar. Inflammation, fibrosis, treatment, prevention, and risk factors have always been the focus in this field.

Vosviewer1.6.18 software was used to cluster the titles and keywords in the abstract of eligible global research literature into different categories, mechanism‐related research, clinical research, diagnostic research, and gene‐related research. Through the time ranking of the clustered literature, we can observe the transfer of the research hotspots and development trends of keloid in the world as well as a leap from case study to integrated analysis. After dividing the research direction, recognising the shift of research hotspot and development trends, and combining the keywords after clustering, we can use the current published literature to explore the results in‐depth.

In terms of pathogenesis, massive case reports and series proved that cutaneous tension and bacterial colonisation within wounds represent a major risk factor for hypertrophic scar formation. 3 Since then, the research on the cellular level and signalling pathway of pathological scar has also been continuously advanced. It is believed that scar hyperplasia and recurrence can be reduced by inhibiting fibroblast proliferation and blocking related signalling pathways after determining the leading proliferating cells (fibroblast) and the signalling pathway (TGF‐β pathway). The latest research is reflected on the molecular level. Some researchers believe that TNF‐α stimulates gene 6(TSG‐6) could effectively interfere the TGF‐β1/Smad signal transduction pathway and inhibit proliferation by inducing apoptosis in keloid fibroblasts rather than in normal fibroblasts. 34 Wang et al. observed that keloid tissues and fibroblasts, relative to normal skin tissues and fibroblasts, exhibited observably upregulated H19 expression and downregulated miR‐29a expression. H19 might facilitate proliferation and metastasis of fibroblasts by modifying downstream miR‐29a and COL1A1. 35 It remains to be verified whether keloids can be treated effectively by upregulating or downregulating the factors that influence keloid formation, such as H19, and TSG‐6. The mechanical force has been shown to be a key regulator of HS formation. He et al. have observed that Piezo1 channel is overexpressed in myofibroblasts of human and rat hypertrophic scar tissue. In vitro, cyclic mechanical stretching (CMS) increased the expression of Piezo1 and Piezo1‐mediated calcium influx in human dermal fibroblasts (HDFs). What's more, intradermal injection of Piezo1 blocking peptide GsMTx4 protected the rats from stretch‐induced hypertrophic scar formation. 36 These relevant signalling pathways, genes, and channel proteins may become targets for the precise treatment of hypertrophic scar in the future.

The study on the mechanism of pathological scar is of great significance for the treatment of scar. Among them, the animal scar model is one of the important methods to study pathological scar at present. The commonly used animal scar models include traditional animal scar models, such as the rodent model, rabbit ear model, and porcine model; however, none of these animal scar models can perfectly simulate the pathological scar formation and healing process of humans. 37 , 38 The rapid development of new technologies such as in vitro transplantation technology, transgenic technology, and tissue engineering technology also provides new ideas and strong support for the construction of scar model. 39 Organs‐on‐chips, which have been widely used in organ and disease models, are highly likely to be used to construct scar models in vitro in future. 40 In addition to using more advanced techniques to simulate pathological scars in humans, further improvements can be made in fields such as genetic susceptibility to scar simulation, which will eventually enable animal scar models to play a greater role in the study of pathological scars.

Meanwhile, the research on the mechanism of pathological scar is also reflected in the improvement of treatment strategies, gradually changing from monotherapy to combination therapy. Autologous fat is definitely a hot topic in scar research in recent years. The number of evidence shows that autologous fat has significant effects on reducing skin fibrosis. Previous research proved ADSCs could promote the rearrangement of collagen I and collagen III, reduce α‐smooth muscle actin deposition, and inhibit scar formation by affecting the relevant signalling pathway of fibroblasts in pathological scar. 41 So far, the exact mechanism of autologous fat injection in the treatment of pathological scar remains for further exploration, but it has shown a good prospect in the field of scar treatment.

Models for the treatment of pathological scars have shifted obviously over the past decade, driven largely by the application of photoelectric technology. 15 In particular, photoelectric therapy combined with drug injection (such as glucocorticoid, 5‐fluorouracil, and adipose mesenchymal stem cells) has achieved remarkable results, especially for patients with a large area of scars. The fractional laser or microplasma radiofrequency could form tiny channels by generating accurate and uniform tissue vaporisation column, which improves the delivery efficiency of drugs permeating the dermis through the skin barrier (cuticle and epidermis), and the depth and density of the skin barrier channels could be adjusted and controlled through different photoelectric treatment modes and parameters, which are predictable. 42 , 43 However, the exact effects need to be further confirmed by more RCT studies of high quality.

To sum up, the pathogenesis and pathophysiological process of scar hyperplasia is still current research hotspots. The relevant genes, signalling pathways, inflammatory factors, and channel proteins are still the focus of the research. Hypertrophic scar‐related clinical studies have shifted from isolated and symptomatic therapy to systematic and sequential therapy, which is proven to make substantial breakthroughs in the treatment of pathological scar.

5. LIMITATIONS

Some limitations are inherent and inevitable in our bibliometric analysis. First, because of the inclusion and exclusion criteria and the software we used to analyse, some high‐quality articles, such as non‐English language articles, conference abstracts, letters, or articles from other databases were excluded from the analysis. Second, some landmark or breakthrough findings were proposed in some earlier literature, which gradually became the consensus of the academic community. Therefore, it may be ignored to cite these previous classical research literature in subsequent literature in related fields, resulting in the inaccuracy of citation frequency. Finally, the academic value of an article should be viewed from a diversified perspective, and only the citation frequency and H value could be one‐sided.

6. CONCLUSIONS

In general, this study analyses the literature on pathological scar research published globally in the last 20 years. China is one of the most prolific countries in the world, which indicates its leading position in this field to some extent. However, the quality of research and international academic cooperation needs to be further strengthened. Wound Repair and Regeneration, Burns, Dermatologic Surgery, Plastic and Reconstructive surgery are the main journals that focus on pathological scars, which suggests some new advances and developments can be found in these journals. Bayat A, Ogawa R, Li Y, and Niessen FB are academic leaders and have the most academic influence in this field. Transforming growth factor‐β TGF‐β1 and its related TGF‐β1/Smad signalling pathway is considered to be most closely related to the formation of hypertrophic scar. In the early stage, the research focus was mainly on the diagnosis and treatment of keloid from individual cases. In the later stage, the research focus was on the systematic management of keloid, in which the mechanism research was in‐depth to the molecular level. We expect that our study could provide relevant researchers with a clear understanding of the current status and trends of pathological scar so as to provide guidance for the basic research and clinical treatment of pathological scar.

AUTHOR CONTRIBUTIONS

Shiyi Li and Minliang Chen contributed to the conception and design of the study; Shiyi Li and Hongfan Ding extracted all data and performed the bibliometric analyses. Yi Yang and Boya Yu performed the validation and graphing of the values in the manuscript. Shiyi Li and Hongfan Ding codrafted the paper. All authors read and approved the final manuscript.

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

FINANCIAL DISCLOSURE STATEMENT

All authors have nothing to disclose.

Supporting information

Table S1 The analytic consequence of 128 keywords with at least 15 occurrence times

Click here for additional data file. (33.8KB, docx)

Li S, Ding H, Yang Y, Yu B, Chen M. Global research status of pathological scar reported over the period 2001–2021: A 20‐year bibliometric analysis. Int Wound J. 2023;20(5):1725‐1738. doi: 10.1111/iwj.13988

Shiyi Li and Hongfan Ding contributed equally to the work.

DATA AVAILABILITY STATEMENT

Supporting data can be obtained from the corresponding author.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Table S1 The analytic consequence of 128 keywords with at least 15 occurrence times

Click here for additional data file. (33.8KB, docx)

Data Availability Statement

Supporting data can be obtained from the corresponding author.

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