Bibliometric Analysis of the Lung Organoids: Trends, Hotspots, and Future Development

introduction: The emergence of 3D culture has provided a platform for organoid generation. As three-dimensional models of self-organizing stem cells, organoids can authentically recapitulate tissue architecture and functionality to a certain extent, along with cell-cell and cell-tissue microenvironment interactions[1, 2]. The lung, being the largest respiratory organ in humans, plays a pivotal role in maintaining physiological homeostasis. Pulmonary diseases including lung cancer, acute respiratory distress syndrome (ARDS), and chronic pulmonary fibrosis significantly impact global health outcomes and impose substantial healthcare burdens[3, 4]. Consequently, research on pulmonary physiology and associated pathologies has become critically important. Lung organoids offer valuable insights into pulmonary developmental processes, while disease-specific models such as lung cancer organoids facilitate investigations into tumor cell interactions and tumor-extracellular matrix crosstalk, establishing platforms for therapeutic screening and toxicological evaluation[5]. In 2010, Nirmalanandhan et al[6]. pioneered the cultivation of lung cancer cells in 3D culture systems for anticancer drug efficacy assessment, marking the nascent stage of lung organoid development despite incomplete characterization of organoid culture protocols. Subsequent years witnessed exponential growth in lung organoid-related research outputs. While existing reviews have summarized current advancements and future directions in lung organoid research[7], comprehensive analyses of evolving research hotspots, international collaborations, and paradigm shifts remain unexplored. A systematic quantitative and qualitative analysis of global lung organoid research, particularly in oncological applications, could provide researchers with critical insights through trend identification, contribution mapping of nations, institutions, authors, and prediction of emerging frontiers. Bibliometric analysis serves as a vital scientific visualization tool that applies statistical principles and mathematical models to quantitatively examine publication patterns within specific disciplines[8]. This methodology not only tracks disciplinary evolution but also identifies research frontiers through knowledge mapping, offering evidence-based guidance for strategic planning. In academic collaboration networks, bibliometric approaches systematically reveal interaction patterns among countries, institutions, and researchers through collaborative network construction, facilitating identification of potential partners and promoting cross-regional innovation[9]. VOSviewer and CiteSpace have emerged as predominant software packages for creating such network visualizations and mapping thematic evolution. This study conducts comprehensive bibliometric analysis using CiteSpace and VOSviewer to elucidate central themes and emerging trends in lung organoid and pulmonary disease research. By focusing on publications from 2010 to 2024, we aim to delineate evolutionary trajectories and contemporary developments in this field. This investigation will synthesize current research priorities and inform future directions, thereby establishing a foundation for subsequent scientific inquiries. materials and methods: 2.1 Data collection The literature data included in this study were obtained from the Web of Science Core Collection (WoSCC) database, with the search conducted on May 1, 2024. A compound search strategy "TS=(lung OR pulmonary OR alveolar) AND TS=(organoids OR organoid OR 3D spheroid)" was implemented to identify relevant publications published between January 2010 and April 2024. A systematic screening process was performed to establish the final research dataset. 2.2 Data analysis The literature search in the WoSCC database retrieved research data including author information, titles, keywords, abstracts, and references. A total of 1721 articles were initially identified. By excluding reviews, conference proceedings, and non-research articles, only original research papers were retained. Subsequent screening based on the relevance of titles and abstracts to the research content was conducted. Ultimately, 1116 articles inconsistent with our research topic were excluded, resulting in 605 original articles. The citation data of these articles were downloaded and saved as "complete records with cited references" in plain text files to facilitate subsequent visual analysis. (As shown in Figure 1) The quantitative variables were analyzed using spreadsheet software (Excel 2021, Microsoft Corporation, Redmond, WA, USA). Visualization and analysis were performed using CiteSpace 6.1.R3 (developed by Chaomei Chen) and VOSviewer 1.68 (developed by Nees Jan van Eck and Ludo Waltman)[10, 11]. VOSviewer 1.68 was employed to calculate publication counts, citation frequencies, and centrality metrics for authors and institutions, while generating keyword co-occurrence networks, reference co-citation networks, and journal co-citation networks. CiteSpace 6.1.R3 was utilized to construct author and institutional collaboration networks, detect keyword bursts and reference citation bursts, and create timeline visualizations of keyword evolution. results: 3.1 General information A literature search identified a total of 1721 articles. After excluding non-research articles, 1265 publications remained. Subsequent exclusion of studies inconsistent with the research focus on lung organoids resulted in 605 final research papers. The successful cultivation of lung-like organs was first reported in 2010, followed by slow but steady progress in related studies during subsequent years. Since 2016, the number of publications related to lung organoid research has increased significantly, indicating growing attention from researchers. Furthermore, the annual citation count exceeded 13798 in 2022, demonstrating intensifying interest in lung organoids. The observed decline in publication and citation numbers for 2024 may be attributed to incomplete statistical data collection (As illustrated in Figure 2). 3.2 National contributions Similar to research progress in pulmonary diseases, lung organoids have attracted extensive attention. A total of 50 countries or regions are closely involved in lung organoid research. A visualization analysis of major countries or regions was conducted to highlight their impact on lung organoid-related research. The United States emerges as the most active contributor to lung organoid studies with 252 published articles, followed by China (132 articles), Germany (52 articles), Japan (52 articles), South Korea (48 articles), the United Kingdom (47 articles), the Netherlands (47 articles), India (25 articles), Italy (24 articles), and Canada (20 articles). In citation rankings, the United States is followed by China, the Netherlands, South Korea, and others. Meanwhile, as depicted in Figure 3, collaborative interactions exist among multiple countries in the field of lung organoid research, with multinational research teams established to further explore new frontiers in this domain. 3.3 Institutional Productivity A total of 1106 institutions have published research on this topic, with 78 institutions contributing more than 5 studies each. The top 5 most cited institutions in this field are Harvard Medical School, University of California, University of Michigan, University of Pennsylvania, and Columbia University. These most contributing institutions are all based in the United States and predominantly represent higher education establishments. Table 1 summarizes the 15 most cited institutions, which are primarily from the United States, China, and Japan. 3.4 Author impact A total of 4710 researchers have published research achievements in this field, with 47 researchers having published over 5 research papers. Spence, Jason R; Dye, Briana R; Morrisey, Edward; Zhou, Su and Miller, Alyssa J are the five most influential scientists. Among them, Spence, Jason R. from the University of Michigan emerges as the most prolific and cited scientist. His publications primarily focus on molecular mechanisms of early lung development, disease modeling and precision medicine applications, as well as recent investigations into regenerative medicine and transplantation potential. This includes CRISPR-Cas9 gene editing for pathogenic mutation correction and assessing post-transplant integration and functional recovery capabilities of organoids. The majority of productive and impactful researchers originate from the United States and China, predominantly affiliated with Harvard Medical School and the University of Chinese Academy of Sciences, respectively. Table 2 summarizes the 15 most cited researchers. 3.5 Keyword clustering and thematic analysis This study extracted a total of 230 keywords related to lung organoids. To visualize research hotspots in this field, we generated a keyword co-occurrence network diagram using VOSviewer software. Based on the network analysis in Figure 4, high-frequency keywords from published articles were categorized into 5 clusters. The green cluster contains primary terminology associated with lung organoid construction, such as stem cells, airway epithelium, and alveoli. The blue cluster explores pathogenesis mechanisms of pulmonary diseases, including pulmonary fibrosis, COPD, and emphysema. The purple cluster primarily focuses on research and applications of lung organoids in COVID-19-related studies. The yellow cluster investigates formation-related pathways and substance release mechanisms of lung organoi