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. 2023 Apr 14:14:1109456.
doi: 10.3389/fendo.2023.1109456. eCollection 2023.

Mapping intellectual structure and research hotspots in the field of fibroblast-associated DFUs: a bibliometric analysis

Yushu Zhu  1   2 , Jianyu Lu  1   2 , Siqiao Wang  3 , Dayuan Xu  1   2 , Minjuan Wu  1   2 , Shuyuan Xian  3 , Wei Zhang  1   2 , Xirui Tong  1   2 , Yifan Liu  4 , Jie Huang  1   2 , Luofeng Jiang  1   2 , Xinya Guo  1   2 , Sujie Xie  1   2 , Minyi Gu  1   2 , Shuxin Jin  1   2 , Yicheng Ma  1   2 , Runzhi Huang  1   2 , Shichu Xiao  1   2 , Shizhao Ji  1   2
Affiliations

Mapping intellectual structure and research hotspots in the field of fibroblast-associated DFUs: a bibliometric analysis

Yushu Zhu et al. Front Endocrinol (Lausanne). .

Abstract

Background: Diabetic foot ulcers (DFUs) are one of the most popular and severe complications of diabetes. The persistent non-healing of DFUs may eventually contribute to severe complications such as amputation, which presents patients with significant physical and psychological challenges. Fibroblasts are critical cells in wound healing and perform essential roles in all phases of wound healing. In diabetic foot patients, the disruption of fibroblast function exacerbates the non-healing of the wound. This study aimed to summarize the hotspots and evaluate the global research trends on fibroblast-related DFUs through bibliometric analysis.

Methods: Scientific publications on the study of fibroblast-related DFUs from January 1, 2000 to April 27, 2022 were retrieved from the Web of Science Core Collection (WoSCC). Biblioshiny software was primarily performed for the visual analysis of the literature, CiteSpace software and VOSviewer software were used to validate the results.

Results: A total of 479 articles on fibroblast-related DFUs were retrieved. The most published countries, institutions, journals, and authors in this field were the USA, The Chinese University of Hong Kong, Wound Repair and Regeneration, and Seung-Kyu Han. In addition, keyword co-occurrence networks, historical direct citation networks, thematic map, and the trend topics map summarize the research hotspots and trends in this field.

Conclusion: Current studies indicated that research on fibroblast-related DFUs is attracting increasing concern and have clinical implications. The cellular and molecular mechanisms of the DFU pathophysiological process, the molecular mechanisms and therapeutic targets associated with DFUs angiogenesis, and the measures to promote DFUs wound healing are three worthy research hotspots in this field.

Keywords: bibliometric analysis; diabetic foot ulcers (DFUs); fibroblast; pathophysiological process; therapeutic targets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Central countries/regions of fibroblast-related DFUs research production and collaboration. The USA and China were the most two influential and contributing countries in fibroblast-related DFUs research. (A) The top 20 countries/regions of fibroblast-related DFUs research with the highest number of publications. (B) Countries/Regions production and collaboration world map of fibroblast-related DFUs research. (C) Single-country and multi-country publications for the top 20 most productive countries/regions.
Figure 2
Figure 2
The Journal of Wound Repair and Regeneration was a critical pathway to access the research frontiers and crucial information of fibroblast-related DFUs research. (A) Core journals of fibroblast-related DFUs research based on Bradford’s Law. (B) The top 20 journals on fibroblast-related DFUs research with the highest number of publications. (C) The six highest yielding journals growth of fibroblast-related DFUs research from 2000 to 2022.
Figure 3
Figure 3
Analysis of high frequency keywords and four research hotspots based on the keyword co-occurrence analysis. (A) Top 10 most frequent keywords growth of fibroblast-related DFUs research from 2000 to 2022. (B) Visualized word cloud map based on the top 50 most frequent keywords for fibroblast-related DFUs research. (C) Visualized keywords co-occurrence network for fibroblast-related DFUs research. Each node indicates a keyword, and the connecting lines between nodes denote the intimacy between keywords. The four clusters were red, blue, green, and purple.
Figure 4
Figure 4
Relationship between high-impact literature and historical evolution and hotspots. (A) The top 20 most global cited documents of fibroblast-related DFUs research. (B) Visualized historical direct citation network based on the evolution trend of fibroblast-related DFUs research from 2000 to 2022. Each node represents a piece of literature, and the lines between the nodes indicate the citation relationships between publications.
Figure 5
Figure 5
Exploring research status of various hot topics on fibroblast-related DFUs, sketching historical trajectories and revealing research frontiers. (A) Thematic map for fibroblast-related DFUs research. The horizontal coordinate refers to the relevance degree (centrality), and the vertical coordinate represents the development degree (density). Motor themes in the first quadrant represents core themes with high centrality and maturity, niche themes in the second quadrant represent isolated themes with increased maturity, the third quadrant represents emerging or declining themes with low centrality and high maturity, and basic themes in the fourth quadrant means popular themes with low maturity. (B) Trend topics map for fibroblast-related DFUs research. Showing trends in the occurrence of high frequency keywords for fibroblast-related DFUs research.
Figure 6
Figure 6
The molecular mechanisms of fibroblast and keratinocyte pathophysiological process in DFUs.The persistent non-healing of DFU wounds is the result of a combination of factors leading to a constant and excessive chronic inflammatory response. In the microenvironment of diabetic wounds, perturbations are associated with hyperglycaemia, advanced glycation end products, oxidative stress and impaired angiogenesis. These factors comprise impaired fibroblasts and disruption of their proliferation, migration, secretion of extracellular matrix and differentiation into myofibroblasts. Meanwhile, there is keratinocyte migration and proliferation, reduced angiogenesis, chronic Inflammation, and abnormal expression of MMPs. Resulting in a constant and excessive chronic inflammatory response, disrupting epithelial cell formation and eventual wound closure. Ultimately leading to the development of chronic non-healing wounds.
Figure 7
Figure 7
The molecular mechanisms of macrophage pathophysiological process in DFUs. Macrophages play a crucial role in routine wound healing, promoting angiogenesis, collagen deposition and wound closure. Over-activation of M1 macrophages and impaired transition from M1 to M2 phenotype are essential differences between normal and diabetic wound healing. In normal wounds, macrophages clear pathogens and cellular debris by activating a pro-inflammatory phenotype. As the inflammatory phase progresses, macrophages shift from pro-inflammatory phenotype to pro-repair phenotype. As a result, it stimulates the proliferation, differentiation and migration of keratinocytes, fibroblasts and endothelial cells by secreting cytokines and growth factors, which directly or indirectly regulate the proliferative phase of the repair process. However, in the microenvironment of diabetic wounds, perturbations associated with hyperglycaemia, advanced glycation end products, oxidative stress and impaired angiogenesis induce disturbances in the immune microenvironment of diabetic wounds, leading to phenotypic dysregulation as well as quantitative, functional, and epigenetic alterations in traumatic macrophages. As a result, M1 polarization is enhanced and the switch from M1 to M2 is severely impaired. This culminates in a situation where lower numbers of M2 macrophages and higher M1/M2 ratios release low levels of growth factors. Meanwhile, the diabetic microenvironment resulted in macrophage sensitivity to pro-inflammatory cytokines and stimulated macrophages to secrete pro-inflammatory cytokines such as IL-1, IL-6, MMP9, and TNF-a. This further exacerbates the vicious cycle of M1 macrophage polarization and chronic inflammation, causing stagnation of the inflammatory phase. Which created an excess inflammatory cytokines microenvironment, ultimately contributed to impaired fibroblast and keratinocyte migration and delayed wound healing.
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