Quantitative analysis of basic informationAnnual publication trend

The number of publications published in the hydrogel biomedical application sector between 1973 and 2024 was recorded in this study. The yearly publication volume data in this discipline indicate an increasing number of publications annually, as Fig. 1 illustrates. As early as 1973, researchers directed their attention towards this field. Subsequently, starting in 2003, there was a steady rise in the number of articles published in this field. However, it was after 2009 that a significant surge in publications occurred, and post-2015 witnessed an exponential rise, indicating a notable shift in researchers’ focus toward this area of study. Remarkably, 294 papers were published in this discipline in 2021, which is an astounding increase of 78 articles over the previous year and a noteworthy rise. Looking ahead to the first year of 2024 alone, already eleven articles have been published thus far, demonstrating its sustained activity. We predict that in 2024, there will be more published papers than 400, which is a demonstration of the researchers’ persistent concern in pursuing and discovering the research potential in this discipline, especially considering the recent quick expansion.

Fig. 1

Annual publication output in the hydrogel biomedical application field from 1973 to 2024

Analysis of published journals

In the literature we selected, we identified the top 10 journals (Table 1) based on their prolific publication records.

Acta Biomaterialia topped the list with 302 articles, Biomaterials came in second with 298 publications, and Frontiers in Bioengineering and Biotechnology came in tenth with 68 publications. In addition to having the second-largest number of articles, biomaterials had the greatest impact factor (14 in 2022) and the highest CiteScore (23.4 in 2022). Biomaterials’ h-index was 418. The h-index is a quantitative metric that assesses the scholarly output of a journal by quantifying the number of highly cited papers and their citation impact. Journals with higher h-indices are generally considered to possess greater academic influence. Biomaterials is a globally recognized journal that focuses on the scientific exploration and clinical applications of biomaterials. Its primary objective is to comprehensively address the multifaceted aspects associated with the utilization of biomaterials in clinical practice, encompassing original research papers, authoritative reviews, and opinion papers. Among the top ten journals, half of them were published by the Elsevier publishing unit. It is evident that Elsevier exhibited a profound interest in this field and in the future, there will be opportunities for researchers who hammered at this domain to consider submitting their articles to the numerous journals of Elsevier.

According to Fig. 1, most works have been published in the past two decades, but there are significant differences in output between these periods. We analyzed the number of articles published by the top 10 journals during 2004–2013 and 2014–2024. Figure 2 illustrates the output of these top 10 journals across 2004–2013, 2014–2024, and overall. Figure 3 reveals that all 10 journals have published significantly more articles in the recent decade (2014–2024), indicating that the application of hydrogels in biomedicine has become a hot research field. Among these journals, Pharmaceutics, Bioactive Materials, and Frontiers in Bioengineering and Biotechnology are particularly noteworthy, as they only began publishing articles in this field after 2017.

Table 1 Top 10 journals with publication output from 1973 to 2024Fig. 2

Publication outputs of the Top 10 journals in the hydrogel biomedical application field during 2004 ~ 2013, 2014 ~ 2024 and overall

Fig. 3

Top 10 publication output journals in the hydrogel biomedical application field in the past 52 years

Cooperative relationship networkCountry cooperation network

We carried out a thorough statistical analysis of the publications from different nations (regions) and organizations. Through our investigation, we successfully identified nations and institutions that exhibited a substantial volume of published papers while exerting significant influence within hydrogel biomedical application field. Furthermore, we meticulously examined the collaborative relationships established among these entities. Articles regarding hydrogel biomedical appliocation were published by 2706 institutions in 79 countries and regions between 1973 and 2024. The top 10 nations were as follows: USA, China, South Korea, Germany, UK, Italy, India, Japan, Canada, and Iran. The top 20 institutions were displayed in Fig. 4. The statistics show that, with 946 papers published and 33.05% papers of all, the USA had the greatest number of articles published. China was not far behind, 791 articles accounts for 27.61% of the entire counts of articles. This indicates that USA and China had leader position in the field of hydrogel biomedical application.

By further analyzing the outputs of the top 20 countries during 2004–2013 and 2014–2024, we present the results in Figs. 5 and 6. Notably, the United States, China, and South Korea have consistently ranked as the top three countries in hydrogel research over the past two decades. This trend aligns with their positions in terms of total publication output over the last 52 years. However, a significant shift has occurred in recent years, particularly within the last decade, where Chinese authors have experienced a remarkable surge in article publications, establishing China as the leading country in terms of sheer volume. Notably, all three countries have seen a substantial increase in published documents in the past ten years compared to the previous decade. Consequently, it is evident that hydrogel applications in biomedicine have become a prominent subject during this period.

Fig. 4

Top 20 countries in the field of hydrogel biomedical application

Fig. 5

Top 20 countries in the field of hydrogel biomedical application during 2004 ~ 2013

Fig. 6

Top 20 countries in the field of hydrogel biomedical application during 2014 ~ 2024

The cooperative relationship between countries was analyzed using the CiteSpace software (Fig. 7). The size of the node corresponds to the citation number of published papers, while the strength of cooperation is indicated by connecting lines between nodes. From nodes’ size, we can have strong evidence which can support the conclusion that the USA and China have incredible influence in this field. As a measure of how strongly a node is connected to other nodes in the network, centrality is an important standpoint in cooperative networks. A high degree of centrality indicates that important nodes have a big impact on the connections within the network. The nodes with purple circle contour have strong centrality. Among these countries, England and Canada held the prominent central position, this shows they both maintained close collaboration. Additionally, India also established robust collaborative partnerships. It is noteworthy that despite the USA and China ranked first and second in terms of paper publication and citation counts, their centrality scores were relatively low, indicating limited international collaboration. This observation may be attributed to their advanced research capabilities.

Fig. 7

Network diagram of national cooperation in the field of hydrogel biomedical application

Institutional Cooperation Network

According to the statistical results of publication numbers and CiteSpace analysis, it is evident that the top 2 institutions in terms of publications are Chinese, thereby emphasizing China’s leadership position in this field (Table 2; Fig. 8). The Chinese Academy of Sciences secured the first rank with a total of 51 publications. Among the top ten institutions in terms of publication amount, four are Chinese institutions. Additionally, four other institutions in the top 10 are from the United States. Hence, both China and the United States wield crucial influence in this field. Although Chinese institutions published marginally more articles than their American counterparts, the disparity was not statistically significant. In the future, Chinese researchers must continue to pursue further studies in this domain to sustain their global leadership position.

Table 2 Top 10 institutions with the counts of publications from 1973 to 2024

In terms of inter-institutional collaboration, we used CiteSpace to identify the top ten institutions based on their citation counts, the results are shown in Table 3. The table illustrates that six out of the ten institutions are affiliated with the United States, they are the University of California System, Harvard University, University of Texas System, University System of Ohio, Stanford University, and Massachusetts Institute of Technology (MIT). The remaining four originate from China, they are the Chinese Academy of Sciences, Shanghai Jiao Tong University, Sichuan University, and Zhejiang University. Both American and Chinese researchers held prominent positions in this field, as their scholarly articles have garnered substantial citations from researchers worldwide.

Table 3 Top 10 institutions with the counts of citations from 1973 to 2024Fig. 8

Institutional cooperation network in the field of hydrogel biomedical application

As previously mentioned, centrality serves as an indicator of the nodes’ influence within the network. We utilized CiteSpace to generate a ranked list of the top ten nodes based on their centralities. The results are shown in Table 4. The majority of institutions exhibiting a high degree of centrality are located in the United States, with only Fudan University from China ranking among the top 10. It is evident that despite Chinese institutions having a substantial number of publications and citations, their impact on inter-agency collaboration remains limited. In the future, China’s numerous research institutions must engage in sincere collaborations aimed at achieving mutual benefits and gradually enhancing their academic influence.

Table 4 Top 10 institutions with the centralitiesAuthor cooperation network

The analysis of the author’s collaboration network revealed that there were a total number of 13,643 researchers who contributed to the investigation of this network in hydrogel biomedical applications. In addition, we can see the rank of the top 20 writers in Table 5 60% of the authors in the table are from the USA, 15% of the authors are from China and 15% of the authors are from Korea. The aforementioned observation provides additional substantiation for the prominent position held by scholars hailing from both the United States. The top 20 scholars all published more than 10 articles. The first one is Professor Burdick Jason A. He is a professor from the University of Colorado Boulder, who published 22 articles in this field. His research fields encompass the development of injectable hydrogels for disease therapy, bioprinting tissue models for therapeutic drug screening, and fabricating fibrous scaffolds for tissue repair.

We analyzed the number of articles published by the top 20 authors during 2004–2013 and 2014–2024. Figure 9 shows the outputs of these top 20 authors for 2004–2013, 2014–2024, and overall. The data presented in Fig. 9 demonstrate that most of the top 20 authors have made significant contributions to the relevant literature within the past decade. Notably, three Chinese authors, Chen Xuesi, Guo Baolin, and He Chaoliang, have published papers on the biomedical applications of hydrogels from 2017 to 2023, indicating their active engagement in this research area for approximately five to six years. This observation aligns with previous studies reporting an increase in articles by Chinese researchers after 2016. Additionally, Professor Tabata Yasuhiko from Japan, Professor Song Soo-Chang and Professor Park Ki Dong from South Korea, and Professor Shea Lonnie D. and Professor West Jennifer L. from the United States have made substantial contributions between 2004 and 2013 regarding the biomedical applications of hydrogels, highlighting Japan, South Korea, and the USA as pioneering nations that laid a solid foundation for subsequent investigations.

Table 5 Top 20 authors in the field of hydrogel biomedical application (1973–2024)Fig. 9

Outputs of the top 20 authors during 2004 ~ 2013, 2014 ~ 2024 and overall

We determined the dispersion and distribution of academics’ collaboration networks by examining their cooperative relationship. (Fig. 10). In contrast to the cohesive national and institutional collaborative networks, the authors’ collaborative networks exhibited a dispersed pattern. A limited number of scholars maintained a closely-knit cooperative relationship primarily based on geographical proximity. For example, Burdick Jason A from the University of Pennsylvania and Reis Rui L from the University of Minho both had strong cooperation with other researchers, and their articles were often referenced. It is worth noting that Burdick Jason A mostly cooperated with researchers from the USA, while Reis Rui L largely cooperated with researchers from Portugal. Tabata Yasuhiko from Kyoto University mostly cooperated with researchers from Japan and Song Soo-Chang from Korea Institute of Science and Technology cooperated with researchers from Korea. The cooperation among authors was predominantly influenced by geographical proximity, as researchers tend to collaborate more frequently with colleagues from their own country. In the future, we anticipate an upsurge in innovative collaborations across nations.

Fig. 10

Network diagram between authors in the field of hydrogel biomedical application

Analysis of discipline evolution

Through comprehensive analysis across various disciplines, we established an intricate network of hydrogel biomedical applications. Figure 11 visually depicts the progression of both mainstream and interdisciplinary fields in this domain, underscoring the extensive coverage of hydrogel biomedical applications across multiple areas. This can be attributed to their significant impact and widespread research focus. Engineering and Biomedical are the main subjects, this is because we are concerned with the biomedical application of hydrogel. The second is Materials Science and Biomaterials, this is because hydrogels belong to a special kind of material, and the advancement of biomaterials has the potential to broaden the scope of hydrogel applications in the field of biomedicine. Pharmacology & Pharmacy and Biotechnology & Applied Microbiology are also important disciplines in this field. From this, it can be inferred that the biomedical application of hydrogels is closely intertwined with pharmacology due to their exceptional performance as drug carriers.

Fig. 11

Disciplinary network in the field of hydrogel biomedical application from1973 to 2024

Moreover, hydrogels exhibit diverse applications in various biotechnologies and demonstrate promising potential against microbial infections. The disciplines that occurred from 1973 to 2024 are included in Fig. 12, which amply illustrates the diverse nature of hydrogel biomedical applications. According to the data, there is a discipline burst in the field of hydrogel biomedical application every 1 ~ 2 years on average; nevertheless, the duration of the developing disciplines burst prior to 2005 is very long. However, the duration of disciplines burst after that is much shorter. This indicates that over the past ten years, there was a growing frequency in the emergence of novel disciplines and continuous identification of research frontiers. Consequently, researchers are urged to diligently monitor the research frontiers to avoid overlooking current trends. Among them, burst disciplines DERMATOLOGY, GENETICS & HEREDITY, PHARMACOLOGY & PHARMACY and FOOD SCIENCE & TECHNOLOGY maintain the longest duration, which is about 10 years, the shortest is ONCOLOGY, CELL BIOLOGY, and CARDIAC & CARDIOVASCULAR SYSTEM, which lasted only one year. The focus of these disciplines lies in the specialized domains of hydrogel medical applications, resulting in a limited number of research innovations. Consequently, the majority of valuable research content will be thoroughly investigated within a span of one to two years.

Fig. 12

Brust disciplines in the field of hydrogel biomedical application during 1973 ~ 2024

Analysis of hotspot evolutionKeywords co-occurrence analysis

Keyword co-occurrence serves as an effective means to reflect the research hotspots within a specific field, while emergent keywords can indicate cutting-edge topics. When analyzing the dispersion of keywords, our initial focus lies on examining the phenomenon of keyword co-occurrence. As depicted in Fig. 13, diverse nodes represent various keywords, with node size denoting the number of associated articles, and lines between nodes representing relationships among these keywords. The intricate interconnections among nodes suggest complex associations. The top ten keywords include delivery, controlled release, in vitro, scaffolds, nanoparticles, differentiation, extracellular matrix, hyaluronic acid, tissue, and mesenchymal stem cells. Among them, delivery is the one with the biggest node and the most intricate web of connecting links.

Subsequently, we performed keyword co-occurrence analysis on literature spanning the periods 2004 ~ 2013 and 2014 ~ 2024, respectively, yielding the depicted results in the Figs. 14 and 15. The top ten keywords in Fig. 14 include drug delivery, controlled release, in vitro, hydrogel, scaffold, growth factor, matrix, differentiation, in vivo and hyaluronic acid. The top ten keywords in Fig. 15 include drug delivery, controlled release, scaffold, in vitro, nanoparticles, hydrogel, injectable hydrogels, stem cell, mesenchymal stem cell and differentiation. Drug delivery and controlled release are frequently mentioned in the three images, indicating that drug delivery has always been a key application field for hydrogels. Additionally, scaffolds are also prominently featured, demonstrating the widespread use of hydrogels in biological scaffold production. In the past decade, new keywords such as nanoparticles have emerged within the top ten, suggesting the emergence of new research areas. For future biomedical research on hydrogel applications and development of new hydrogels, greater attention should be given to nano-hydrogel development and application as well as injectable hydrogels. Furthermore, in the field of hydrogel applications, more emphasis should be placed on utilizing novel hydrogels with stem cells, particularly mesenchymal stem cells.

Fig. 13

Co-occurrence keyword network in the field of hydrogel biomedical application. (1973 ~ 2024)

Fig. 14

Co-occurrence keyword network in the field of hydrogel biomedical application. (2004 ~ 2013)

Fig. 15

Co-occurrence keyword network in the field of hydrogel biomedical application. (2014 ~ 2024)

Keywords cluster analysis

Cluster analysis of keywords was performed on all articles (1973 ~ 2024) within the hydrogel biomedical application field (Fig. 16). Keywords exhibiting similarities were grouped, while distinct clusters were formed for each keyword. The number of keywords within each cluster decreased as the sub-cluster number increased, with each cluster comprising multiple closely associated terms. Furthermore, co-occurring keywords were categorized into 20 sub-clusters, denoted by numbers ranging from 0 to 19, including #0 stem cells, #2 tissue engineering, #3 wound dressing, #4 cartilage regeneration, #5 bone generation, #6 hyaluronic acid, #7 drug delivery, #8 antibacterial property, #9 controlled release, #10 wound healing, #11 combination therapy, #12 myocardial infarction, #13 culture, #14 nucleus pulposus, #15 volumetric muscle loss, #16 diabetic wound healing, #17 gellan gum, #18 nerve regeneration, #19 osteogenesis.

We also performed cluster analysis on literature spanning the periods 2004–2013 and 2014–2024. Figures 17 and 18 present the results. The keywords in articles published during 2004–2013 can be grouped into 15 clusters: #1 drug delivery system, #1 controlled release, #2 bone formation, #3 intervertebral disc, #4 tissue engineering, #5 hyaluronic acid, #6 drug delivery, #7 nucleus pulposus, #8 alginate, #9 chitosan, #10 cell delivery, #11 biodegradable polymers, #12 drug release, #13 release, #14 myocardial infarction. For the period 2014–2024, the keywords can be grouped into 17 clusters: #0 tissue engineering, #1 bone regeneration, #2 wound healing, #3 vascular endothelial growth factor, #4 combination therapy, #5 drug delivery, #6 myocardial infarction, #7 hyaluronic acid, #8 spinal cord injury, #9 adipose-derived stem cells, #10 three-dimensional bioprinting, #11 extracellular matrix, #12 thermos-responsive gels, #13 composite hydrogel, #14 peritoneal metastases, #15 skin fibroin, #16 mesenchymal stromal cells. Through tertiary cluster analysis, we identified recurring labels for hydrogel applications, including tissue engineering, controlled release, drug delivery, and hyaluronic acid. These reiterated labels accurately reflect the principal domains where hydrogels are employed. Notably, wound healing and bone regeneration have emerged as significant applications in the past decade. These two areas encompass numerous keywords, indicating a heightened research focus on utilizing hydrogels for these purposes in recent years. This also suggests potential directions for future investigations.

Fig. 16

Co-occurrence clustering keyword network in the field of hydrogel biomedical application. (1973 ~ 2024)

Fig. 17

Co-occurrence clustering keyword network in the field of hydrogel biomedical application. (2004 ~ 2013)

Fig. 18

Co-occurrence clustering keyword network in the field of hydrogel biomedical application. (2014 ~ 2024)

Bursting keywords are frequently referenced over a specific period. CiteSpace can identify bursting keywords, which serve as a foundation for assessing the forefront of research. We used Fig. 19 to show our results. The timeline is depicted by a green line, with the bold red section indicating the temporal phase of the keyword outbreak. It signifies the year when the keyword originated, ceased, and its duration of prominence. The top 25 keywords based on their duration include controlled release (1998 ~ 2013), microspheres (2003 ~ 2012), growth factor (2004 ~ 2012), surface (2005 ~ 2013), in vivo (2006 ~ 2010), gene therapy (2007 ~ 2013), gene delivery (2008 ~ 2018), progenitor cells (2009 ~ 2016), protein delivery (2010 ~ 2013), transplantation (2011 ~ 2014), block copolymers (2012 ~ 2014), regenerative medicine (2014 ~ 2018), biomedical application (2016 ~ 2018), microenvironment (2017 ~ 2020), photothermal therapy (2020 ~ 2024), antioxidant (2020 ~ 2024), oxidative stress (2020 ~ 2024), inflammation (2021 ~ 2024), PH (2021 ~ 2024), injectable hydrogels (2021 ~ 2022), photodynamic therapy (2021 ~ 2022), injury (2021 ~ 2024), antibacterial (2022 ~ 2024), 3d bioprinting (2022 ~ 2024) and adhesive (2022 ~ 2024).

Fig. 19Analysis of co-citationAnalysis of author co-citation

We utilized CiteSpace software to analyze a total of 2862 articles published between 1973 and 2024, employing a time slice of one year. From each time slice, we selected the most frequently cited or referenced entries. Figure 20 presents the co-citation network diagram of the author, comprising 1320 nodes and 4353 lines. These nodes represent the references under analysis while the lines depict co-citation relationships among documents. Larger nodes indicate studies that have been cited more frequently over time. The amounts of citations in various periods are indicated by the color and thickness of the circles within the nodes. The colors of the lines match the time slices exactly; the more recent years are represented by warmer hues and the earlier years by cooler hues. The first-ranked authors are PEPPAS NA et al. with a citation number of 278, followed by LEE KY et al. with a citation number of 214, BURDICK JA et al. with a citation number of 155, and HOFFMAN AS with a citation number of 149.

Nicholas A. Peppas is a distinguished chair professor at the University of Texas at Austin. He spearheaded groundbreaking advancements in biomaterials, nanomaterials, polymer physics, drug delivery, and bio-nanotechnology through his multidisciplinary approach. Professor Peppas established fundamental principles and a rational design methodology for biomedical systems while also developing controlled-release devices and models for drug and protein diffusion in biological tissues. His exceptional contributions to the fields of biomaterials, controlled drug release, and bio-nanotechnology have earned him global recognition as one of the foremost scientists in these areas.

Fig. 20

Author co-citation analysis in the hydrogel biomedical application field

Analysis of document co-citation

We used CiteSpace software to analyze a total of 2862 articles published between 1973 and 2024, with a time slice of one year. Figure 21 shows the visualization analysis results. Table 6 shows the Top 10 ranked articles by co-citation counts. The top-ranked document by citation counts is Jin Qu’s article with 48 citation counts: “Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility, and compressibility as wound dressing for joints skin wound healing” (DOI: https://doi.org/10.1016/j.biomaterials.2018.08.044). The first author is Jin Qu from the State Key Laboratory for Mechanical Behavior of Materials, Frontier Institute of Science and Technology, Xi’an Jiao Tong University, China. In this article, the authors introduce an injectable hydrogel possessing antibacterial adhesion properties and appropriate mechanical properties, which can serve as a wound dressing for joint or skin healing. A series of hydrogels were synthesized by cross-linking dynamic Schiff bases and co-polymer micelles within a single system and mixture of quaternized chitosan (QCS) and benzaldehyde-terminated PluronicF127 (PF127-CHO) under physiological conditions in this study. These hydrogels exhibited desirable tensile and compressive properties, with a semblable modulus compared to that of human skin, excellent adhesion, and rapid self-healing ability. Moreover, they also demonstrated favorable hemostatic characteristics and excellent biocompatibility. Additionally, curcumin was incorporated into the hydrogel matrix, displaying remarkable antioxidant capacity along with pH-responsive release behavior. In vivo experiments conducted on a full-thickness skin defect model revealed that the curcumin-loaded hydrogel significantly accelerated the wound healing process while promoting increased thickness of granulation tissue deposition and collagen synthesis; furthermore, it upregulated vascular endothelial growth factor (VEGF) levels in the treated area. Consequently, this antibacterial adhesive hydrogel dressing possessing self-healing capability alongside superior mechanical properties exhibits immense potential for application in joint skin wound healing [21].

Fig. 21

Document co-citation analysis in hydrogel biomedical application

Table 6 Top 10 co-cited documents in hydrogel biomedical applicationAnalysis of patents

The patent data comes from the incoPat technology innovation information platform of Beijing IncoPat Co., Ltd., which is the first patent database in China with independent intellectual property rights. The search mode used was: “TIAB=(hydrogel?) AND (USETT-CLASS1-CN=(“Medicine and medical treatment”)) AND ((USETT-CLASS1-CN=(“disease”))”. We searched 3,469 patents from 1982 to 2024 and visualized the results.

Application trend analysis

Figure 22 depicts the trend in the number of patent applications, providing a macro-level understanding of their popularity fluctuations over different time periods. The term “number of applications” refers specifically to patents that have been published. It is important to note that general invention patents are disclosed between 3 and 18 months after application, while utility model and design patents are typically disclosed approximately 6 months after application. Overall, the number of patent applications related to hydrogel biomedical applications has shown a growth trend, which can be categorized into three stages: slow development (1982–1995), rapid development (1996–2011), and sustained growth (2012–2024)

The initiation of patent applications related to hydrogel biomedical applications dates back to 1982. From 1982 to 1995, the annual global count for such patent applications remained relatively low, with fewer than 30 filings per year, reflecting a slow pace in technological advancements and a lack of significant industrial scale formation. Since 1996, there has been a substantial increase in the annual global filing rate for patents related to hydrogel biomedical applications. As technology progressed, awareness regarding intellectual property protection among technical experts gradually developed, leading to increased demand. The peak in annual global patent application filings related to hydrogel biomedical applications was observed in 2011, with 183 submissions. From 2012 onwards, the yearly count for global patent applications consistently exceeded 100 as technology matured and stable growth persisted. Particularly during the period from 2012 to 2017, numerous patents emerged within this field, driving technological advancements. Staying updated on these trends will facilitate targeted technological innovation.

Fig. 22