A total of 8,243 articles were collected from the Web of Science database. Among them, book chapters (57 articles), proceeding papers (29 articles), early access publications (12 articles), meeting abstracts (9 articles), editorial materials (24 articles), retracted publications (14 articles) and others (2 articles) were excluded. Additionally, 26 non-English studies were excluded. Finally, 8,070 articles met the inclusion criteria for the Web of Science database (Figure 1). We summarized the global literature trends (Figure 2A). From 2013 to 2015, the annual publication counts steadily increased from 496 to 672. After 2016, the annual count fluctuated, peaking at 872 publications in 2020. Despite a slight decline in subsequent years, the overall trend in cumulative publications shows continuous growth, surpassing 8,000 by 2023. The top five countries with the highest number of articles are China (3,006 articles, 37.249%), the USA (1,668 articles, 20.669%), South Korea (545 articles, 6.753%), Germany (462 articles, 5.725%), and Japan (457 articles, 5.663%) (Table 1).

We collected a total of 8,070 articles involving 38,062 authors and visualized their collaboration networks (Figure 3A), emphasizing the co-authorship connections among the top seven authors (Figure 3B). The collaborative relationships between key authors were further analyzed using CiteSpace (Figure 3C). By examining the co-cited authors, we identified “Caplan A. I.,” “Dominici M.,” “Friedenstein A. J.,” “Liu Y.,” and “Pittenger M. F.” as the top five authors with the highest total connection strength, suggesting they may be central figures in the field (Figure 3D). Citation bursts, which indicate periods of frequent citations, revealed that these authors have experienced significant attention over time, serving as an important metric for their impact. The top 20 most-cited authors demonstrated the strongest citation bursts in publications related to mesenchymal stem cell applications (Figure 3E). “Amini Ami R.” ranked first with a burst strength of 29.34, followed by “Hare J. M.” with a burst strength of 22.25. Notably, “Pittenger M. F.” had the longest duration of citation bursts, spanning over 8 years (2015–2023). Interestingly, our analysis of the top 10 authors with the most publications revealed that nine out of the 10 are based in China (Table 2). Additionally, we summarized the top 10 funding agencies supporting research in this field (Table 3).

In the co-authorship countries visualization shown in Figure 4A, it can be observed that the United States (strength = 579) has the highest total connection strength, followed by China (strength = 443), Germany (strength = 175), and Japan (strength = 121). In terms of publication output, China leads with 3,006 articles, followed by the United States (1,668 articles), South Korea (545 articles), Germany (462 articles), and Japan (457 articles) (Table 1). There is a relatively close collaboration among China, the USA, South Korea, Germany, and Japan (Figure 4B). Table 4 lists the top 10 institutions publishing the most related literature, with Shanghai Jiao Tong University ranked first, followed by Sichuan University and the Chinese Academy of Sciences. These results are also reflected in Figure 4C. Among these institutions, there are relatively close connections between the Chinese Academy of Sciences, Shanghai Jiao Tong University, Sun Yat-sen University, Southern Medical University, and Sichuan University (Figure 4D).

In this study, we identified 10 key research fields related to the topic (Table 5). Among these, Cell Biology had the highest number of publications (2,273 papers, H-index = 111), followed by Materials Science (2,197 papers, H-index = 126) and Engineering (1,762 papers, H-index = 108). The top 10 journals by publication volume were also identified, with Stem Cell Research and Therapy leading with 237 articles (impact factor = 7.1, 2023), followed by the International Journal of Molecular Sciences with 228 articles (impact factor = 4.9, 2023), and Acta Biomaterialia with 195 articles (impact factor = 9.4, 2023). Other notable journals included Biomaterials (192 articles, impact factor = 12.8, 2023) and Stem Cells International (162 articles, impact factor = 3.8, 2023). Interestingly, the publication numbers across these journals were relatively similar (Table 6).

We conducted a visual analysis of reference citations across journals (Figure 5A) and performed co-clustering analysis using CiteSpace (Figure 5B). Key research hotspots identified include “mesenchymal stem cells,” “graphene oxide,” and “bone tissue engineering.” Using VOSviewer, we visualized the citation relationships among journals (Figure 5C), with the top five journals by total link strength being Biomaterials (2,717,148), Acta Biomaterialia (1,173,617), Stem Cells (895,597), PLoS One (841,759), and Tissue Engineering Part A (807,800). Additionally, we highlighted the top 15 journals with the highest citation rates in publications related to mesenchymal stem cell therapy for bone regeneration (Figure 5D).

Figure 4E shows the citation frequency by different countries and regions, with China leading at 2,432,564 citations, significantly ahead of the USA (2,344,484 citations), South Korea (661,042 citations), Italy (678,669 citations), and Germany (838,267 citations). Among the top 10 countries and regions with the highest average citation frequency (Table 1) (Figure 2B, 2C), the USA has the highest average citation frequency (48.04 citations), followed by England (45.85 citations), Italy (45.35 citations), India (38.38 citations), and South Korea (38.11 citations). We also analyzed the top 10 countries with the highest H-index in related publications (Figure 2D), with China (H-index = 130) and the USA (H-index = 125) leading, followed by South Korea (H-index = 72), Italy (H-index = 68), and Germany (H-index = 65).

We conducted a keyword network visualization of the collected articles (Figure 6A). Among the 19,426 keywords, the top five with the highest total connection strength are “mesenchymal stem cells” (total link strength = 24,809), “differentiation” (total link strength = 16,154), “regeneration” (total link strength = 15,189), “in vitro” (total link strength = 14,407), and “bone-marrow” (total link strength = 12,233). We also visualized these keywords based on their average publication year (Figure 6B). Using CiteSpace, we created a visualization of these keywords (Figure 6C) and performed cluster analysis to establish a visual clustering of keywords (Figure 6D). Finally, we identified the 20 keywords with the most significant citation growth, finding that “extracellular vesicles” had the most significant citation growth strength (strength = 43.93, 2021–2023) (Figure 6E).

A total of 128 out of the 261,144 cited references meet the threshold of being cited at least 80 times (Figure 7A). Among the top 5 most cited review articles (Table 7), “Clinical trials with mesenchymal stem cells: an update” was cited 1,023 times (24), followed by “Materials design for bone-tissue engineering” cited 1,016 times (25) and “Alginate-based biomaterials for regenerative medicine applications” cited 907 times (26). In the top 5 most cited research articles (Table 8), “Bone substitutes in orthopaedic surgery: from basic science to clinical practice” was cited 772 times (27), “Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial” was cited 651 times (28) and “Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression” was cited 577 times (29). We performed co-cited references visualization for this field using CiteSpace (Figure 7B) and conducted a cluster visualization analysis of the references (Figure 7C) and found that “extracellular vesicles,” “cardiac regeneration,” and “bone tissue engineering” are hot topics in the references.

Our team conducted a bibliometric analysis of papers published between 2013 and 2023 to explore the progress and future directions in the field of mesenchymal stem cells for bone regeneration. During this period, the global number of papers on this topic showed a fluctuating upward trend, with a peak of 872 papers published in 2020. Although the number of papers published annually has generally increased, this trend was not statistically significant. On a global scale, China and the United States published far more papers than other countries/regions, together accounting for more than 50% of the total papers published in this field worldwide. Interestingly, we found that nine out of the top 10 authors with the highest citation counts were all from China. Furthermore, not only did China publish more papers than the U.S., but its H-index also surpassed that of the U.S., reflecting the significant contributions made by Chinese researchers in this field. However, in terms of average citation count, China ranked 7th, indicating that while China has a large number of papers, the academic impact of each paper is relatively lower. It is also worth noting that only four Chinese institutions appeared in the top 10 institutions by publication volume. This suggests that to enhance a country’s academic standing, it is not only necessary to establish top-tier research institutions and increase research investment but also to focus on improving research quality and avoiding an overemphasis on quantity.

Among the top 10 journals in this field, the leading ones focus on Cell Biology, Materials Science, Engineering, and Research Experimental Medicine. “Cell Biology” and “Materials Science” not only publish a large number of articles but also have high H-indices. This indicates that in this field, authors are more inclined to focus on cell biology and materials, which are highly relevant to the topic.

Highly explosive keywords can predict emerging directions. The current network reflects all keywords included in publication titles or abstracts, which we divide into two parts: mesenchymal stem cells and bone regeneration by tissue engineering.

Based on the above analysis and illustrations, we can observe that over the past 10 years, mesenchymal stem cell (MSC) therapy in the field of bone regeneration has mainly gone through a process from basic research to applied research, and then to clinical application. Early research by scientists was primarily focused on the basic characteristics and differentiation mechanisms of cells, which laid a solid foundation for future studies. During the mid-term phase, the focus shifted towards exploring methods to optimize differentiation and proliferation conditions. With the continuous advancement of technology, researchers have increasingly concentrated on clinical applications and personalized treatment strategies. For instance, they have utilized various technologies to enhance the targeting of MSCs and have developed personalized stem cell treatments tailored to the individual, aiming to improve therapeutic outcomes.

Despite some progress, several challenges remain in using MSCs for bone regeneration therapy. Firstly, issues related to cellular aging and functional decline during in vitro expansion affect not only MSCs derived from patients but also allogeneic MSCs from healthy donors (61). Secondly, the immune response is another critical issue, as the efficacy of MSC transplantation is significantly influenced by the patient’s immune status, and allogeneic MSC transplantation may trigger immune rejection (62). Additionally, although technical advancements have improved cell viability, the post-implantation survival rate remains a pressing issue.

To overcome these challenges, future research needs to further explore and develop new strategies and methods. This includes improving in vitro expansion techniques to minimize cellular aging, optimizing immunomodulatory strategies to reduce the risk of immune rejection, and enhancing the survival rate and functionality of MSCs in vivo. Through these efforts, MSC targeted therapies are expected to achieve safer and more effective applications in the field of bone regeneration.

This study employed bibliometric and visualization analysis methods to explore the literature on mesenchymal stem cell therapy for bone regeneration over the past 10 years. While our findings are comprehensive and objective, there are inevitable limitations. Firstly, we used only the Web of Science Core Collection (WOSCC) for literature retrieval, excluding other databases such as PubMed, Scopus, Cochrane, and Embase. Although WOSCC is a widely used authoritative comprehensive database, this may have led to the omission of some relevant literature, resulting in potential selection bias. Secondly, we excluded non-English literature and non-research/review articles, which may overlook relevant studies published in other languages. Chinese publications, in particular, have made significant contributions in this field. Review and research articles are valuable publication types, each with its unique role and value. Therefore, we did not separately discuss research and review articles. Furthermore, we did not include articles published after January 2024, which may introduce a degree of predictive bias in the relevance analysis. Lastly, we did not consider the quality of the publications in certain analyses, treating high-quality and low-quality publications equally.