Exosomes promote diabetic wound healing: a visual analysis of research hotspots and evolutionary trends

Abstract

BACKGROUND: Diabetes wound is one of the serious complications of diabetes patients, and its complex pathological mechanism and clinical treatment dilemma is still a major challenge. In recent years, exosomes have become a new focus in the field of diabetes wound research because they play a key role in intercellular communication, immune regulation, and tissue repair. OBJECTIVE: To investigate the research hotspots and evolutionary trends of exosomes in diabetic wound healing. METHODS: A systematic search was conducted in the Web of Science core collection to identify English literature focusing on exosomes in diabetic wound healing and published between the inception of the database and December 31, 2024. The annual publication volume was analyzed to track changes over time. Visual analyses using VOSviewer and CiteSpace software were performed on the retrieved literature to examine key aspects such as authors, countries, institutions, journals, and keywords, providing insights into the current research landscape and evolving hot topics in exosomes for diabetic wound healing. RESULTS AND CONCLUSION: From 2014 to 2024, a total of 424 publications on exosome-promoted diabetic wound healing were produced, contributed by 2,883 authors from 46 countries and featured in 199 journals. In the realm of exosome-promoted diabetic wound healing, China had the highest number of publications, followed by the United States. The journals 'Journal of Nanobiotechnology' and 'Advanced Healthcare Materials' published the most papers and had high influence. Author Chen Zhenbing and Huazhong University of Science and Technology were the most productive author and institution, respectively, but the researcher clusters have not yet reached a certain scale, and future collaboration needs to be strengthened. Global research focus mainly concentrated on 10 thematic clusters including adipose stem cells, diabetic wounds, diabetic wound healing, wound healing, endoplasmic reticulum stress, microvesicles, collagen, proteomics, and diabetic foot infection. The research hotspots in this field are undergoing a transition from molecular mechanisms to systematic interventions. Future research hotspots will focus on angiogenesis, macrophages, antibacterial, and hydrogels. On this basis, integrating multidisciplinary technologies to achieve more effective precision treatment and optimize management strategies for diabetic wounds.

1. Introduction

Diabetic wounds are a serious chronic complication that significantly impacts patients across different countries, ages, and genders, consuming substantial global health resources [1-2]. Normally, the wound healing process involves four stages: hemostasis, inflammation, proliferation, and remodeling [3]. However, due to the long-term hyperglycemic environment in diabetic patients, wounds exhibit persistent inflammation, impaired angiogenesis, and dysregulated extracellular matrix remodeling, leading to impaired healing [4-6]. Consequently, diabetic wounds often fail to heal spontaneously. Diabetic foot ulcers are the most severe type of diabetic wounds. According to statistics, the incidence of diabetic foot ulcers in diabetic patients ranges from 7.2% to 15%, with 50%-60% of ulcers developing secondary infections that may require amputation in severe cases. The 5-year mortality rate for patients with diabetic foot ulcers is approximately 30%, and for those undergoing amputation, the mortality rate exceeds 70% [7]. This phenomenon imposes a huge burden on patients and healthcare systems, especially as the number of diabetic patients continues to rise.

Exosomes are cell-derived nanovesicles that carry proteins, lipids, nucleic acids, and other substances, secreted by cells under physiological and pathological conditions [4,8-9]. Recent studies have shown that exosomes can improve wound healing by accelerating angiogenesis, collagen deposition, and re-epithelialization, offering great promise for diabetic wound treatment [10-12]. For instance, SONG et al. [13] demonstrated that adipose-derived stem cell exosomes effectively reduce inflammation and promote angiogenesis, thereby accelerating diabetic wound healing. Notably, in the field of wound repair, the combination of exosomes with biomaterials has become a research hotspot. Exosomes can serve as carriers of bioactive molecules and, when modified or loaded into biomaterials, can modulate the microenvironment and activate wound repair mechanisms [14-15]. WENG et al. [16] showed that a multifunctional hydrogel dressing loaded with mesenchymal stem cell exosomes and macrophage exosomes significantly promoted diabetic wound healing through synergistic anti-inflammatory, antioxidant, pro-angiogenic, and macrophage immune-regulating mechanisms. LI et al. [17] designed an anti-swelling hydrogel system with functionalized gold nanorods and M2 macrophage-derived exosomes, achieving antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic effects via near-infrared photothermal synergy, with promising results in diabetic oral mucosal ulcers and full-thickness skin defect models. Furthermore, overexpression of exosomal contents (e.g., miRNAs) is also an important direction in tissue engineering research. HUANG et al. [18] showed that engineered exosomes overexpressing miR-31-5p effectively promoted angiogenesis, fibrogenesis, and re-epithelialization by targeting hypoxia-inducible factor inhibitor and epithelial membrane protein 1.