2.1 Data source and Retrieval strategy

Utilizing the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database, we conducted a comprehensive search for relevant literature. To ensure the accuracy and completeness of the data, we performed both the literature search and data extraction on the same day, thereby minimizing potential biases from database updates. To enhance the precision and breadth of the search, we developed a search strategy based on Medical Subject Headings (MeSH) terms and Entry Terms. The specific search query used was: “articular cartilage∗” AND (repair∗ OR regenerat∗) AND (“knee osteoarthritis” OR “osteoarthritis of knee” OR “osteoarthritis of the knee”), with the search restricted to articles or reviews in English published between 2004 and 2023. After screening and excluding literature unrelated to the research topic, a total of 682 publications were identified for inclusion in the study.

2.2 Bibliometric analysis

We exported the retrieved literature data, saving it in both plain text format (“download_xxx.txt”) and tab-delimited file format. Initially, we imported the plain text file into CiteSpace 6.2. R4 for data deduplication, which revealed no duplicate records. Subsequently, we employed software tools including VOSviewer 1.6.19, CiteSpace 6.2. R4, and Pajek 5.18 for constructing scientific knowledge maps and conducting data statistical analyses. Additionally, the tab-delimited file was uploaded to an online bibliometric analysis platform to generate a knowledge map of country/region collaboration networks. During the VOSviewer analysis, we set the minimum publication thresholds to 5 for countries/regions, 6 for institutions, and 5 for authors. For journals, documents, and authors, we established minimum citation thresholds of 150, 20, and 50, respectively. The minimum frequency threshold for keywords was set to 20. For CiteSpace, the time span was set from January 2004 to December 2023, with time slices of 2 years. Keywords, categories, and references were selected as node types, with the top 50 nodes per time slice used for analysis. All other parameters were maintained at their default settings.

3.1 Analysis of annual publications and citations

This study encompasses a total of 682 relevant publications, the majority of which are research articles focused on specific issues (479 papers, accounting for 70.23 %), while the remainder are review articles summarizing advances in the field (203 papers, accounting for 29.77 %). Collectively, these publications have contributed to the development of the field's knowledge base and have received extensive academic recognition, with a total citation (TC) count of 28,517. The average citation per paper (ACPP) is 41.81, indicating a high overall academic value of these works. The H-index stands at 79, further highlighting the concentration and impact of high-quality research outputs in this domain. Fig. 1 provides a visual representation of the annual publication volume and citation frequency in this research area over the past 20 years. The data demonstrates a marked increase in both annual publication volume and citation frequency. Notably, in the past five years (2019–2023), compared to the previous five years (2004–2008), the annual publication volume has risen by a factor of 8.2–64 articles, while the citation frequency has surged 73.6-fold to 3575 citations. This dramatic growth not only reflects the continuous emergence of research hotspots in the field but also signifies the active engagement and contributions of researchers, collectively driving the rapid advancement and accumulation of knowledge. Furthermore, it underscores the complexity and challenges associated with research problems in this field, highlighting the need for continued efforts and exploration to achieve breakthrough advancements.

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Fig. 1 Trends in publications and citations.

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3.2 Analysis of countries/regions and institutions

This study provides a comprehensive analysis of academic literature produced by 1279 research institutions across 57 countries/regions worldwide. Fig. 2 visually illustrates the evolution of annual publication volumes from the top ten high-output countries/regions. It is evident that the United States has been the principal contributor over the past two decades. In contrast, China initially exhibited a slower research pace, with limited annual publication output. However, thanks to strategic national directives and substantial financial support, China's annual publication volume successfully surpassed that of the United States in 2018 and again in 2021, establishing itself as the most productive nation. Fig. 3 reveals the scientific research interactions among countries/regions through a collaboration network diagram, where the size of the colored blocks reflects the volume of publications and the connecting lines represent collaborative relationships.^10–12 Clearly, both the United States and China not only dominate in terms of publication volume but also demonstrate a superior capacity for building extensive international collaboration networks, with the United States particularly excelling in this regard. Further, Fig. 4A focuses on countries/regions with research outputs meeting a minimum threshold of five publications. By employing various visual elements such as node size, line thickness, and color variation, it multidimensionally showcases each nation's research strength, collaboration intensity, and the timeliness of research.^13–15 The diagram illustrates that traditional research powerhouses such as the United States, the United Kingdom, Germany, and France established a solid theoretical foundation early on. In contrast, China, through recent relentless efforts and notable achievements, has emerged as a leading force driving in-depth development in the field. Fig. 4B reinforces the core positions of the United States and China within the field, highlighting their critical importance on the global research map. Table 1 provides a detailed overview of the research profiles of the top ten high-output countries/regions. The United States leads with 192 publications, commanding an impressive 28.15 % share, firmly holding the top position. China follows closely with 169 publications, contributing 24.78 %, with the two countries collectively accounting for over half of the total publication volume, thus emerging as the dominant forces in the field. Moreover, the United States excels in various metrics including TC, ACPP, H-index, and total link strength (TLS). Particularly, its leading positions in the H-index and TLS not only underscore the broad impact and recognition of its research outputs but also reflect the depth and breadth of its international collaboration network, notably with China, Germany, Switzerland, the United Kingdom, and the Netherlands. This collaborative network has significantly advanced global scientific research. For China, despite achieving publication output comparable to the United States, there remains room for improvement in indicators reflecting academic influence such as ACPP. This suggests that the Chinese research community needs to focus on enhancing research quality and deepening international collaborations while maintaining high growth in publication output. By strengthening exchanges and cooperation with international research institutions, adopting advanced research methodologies and technologies, and improving the innovativeness and impact of research findings, China aims to play a more prominent and leading role on the global research stage.

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Fig. 2 Trends in publications from the top 10 high-yield countries/regions.

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Fig. 3 Knowledge map of national/regional cooperation networks.

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Fig. 4 (A) Time overlay of national/regional cooperation networks. (B) Density map of national/regional cooperation networks.

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In the analysis presented in Fig. 5, we examine the collaborative network structure of institutions that have produced six or more academic outputs and provide a detailed depiction of the distribution of these institutions' average publication times. Furthermore, Table 2 meticulously enumerates the key metrics of the top ten high-output institutions. In the early stages of the discipline's development, pioneering institutions such as the University of California System, Harvard University, Cornell University, Rush University, University of London, and Duke University laid a solid foundation for the field through their early academic contributions. In recent years, institutions from China, including the Chinese University of Hong Kong, Sichuan University, Sun Yat-sen University, and Southern Medical University, have demonstrated a robust upward trajectory, emerging as significant new players in the research domain. Specifically, the University of California System leads with a remarkable 21 publications, accounting for 3.08 % of the total, underscoring its leadership position in the field. It is followed by Harvard University and Utrecht University, which have achieved 17 (2.49 %) and 16 (2.35 %) publications, respectively, consolidating their positions at the academic forefront. The University of California System not only excels in publication volume but also stands out in key metrics such as TC, H-index, and TLS, demonstrating its profound academic impact and extensive international collaboration network. Cornell University, despite ranking seventh in publication volume, achieves the highest ACPP, reflecting the high quality of its research outputs and their broad recognition within the academic community. This establishes Cornell as a core research institution in the field. Notably, the majority of these high-output institutions are located in the United States and China, with the notable performance of U.S. institutions further reaffirming the leadership and outstanding contributions of these two countries in the research domain.

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Fig. 5 Time overlay of institutional collaboration networks.

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3.3 Analysis of authors

A total of 3770 researchers have contributed to the publication of literature in this research domain. Fig. 6A provides a visual representation of the collaboration network among scholars who have each contributed at least five papers, along with the distribution of their average publication times. Table 3 offers a detailed overview of the key information for the top ten most active authors in the field. The data reveals that Koh YG from Yonsei Sarang Hospital in South Korea leads with nine publications, accounting for 1.32 % of the total output, highlighting his exceptional research productivity. He is followed by Link TM from the University of California System, Kim YS from Yonsei Sarang Hospital, and Filardo G from IRCCS Istituto Ortopedico Rizzoli in Italy, each with eight publications, collectively contributing 1.17 % of the total, demonstrating their strong research capabilities. Notably, Koh YG and Filardo G excel not only in publication volume but also in key evaluation metrics such as TC, ACPP, and H-index, underscoring their prominent positions as core scholars in the field. Their research outputs are widely disseminated and deeply impactful, significantly advancing the high-quality development of the discipline. Additionally, Eckstein F from Paracelsus Private Medical University in Austria stands out with the highest TLS, reflecting his remarkable achievement in establishing an extensive academic collaboration network, particularly with scholars such as Wirth W, Majumdar S, Link TM, and Lafeber FPJG. This further solidifies his academic standing in the field. Furthermore, Eckstein F, Wirth W, Majumdar S, Link TM, and Choi YJ laid a solid theoretical foundation through their early research, and their high academic influence continues to resonate. In recent years, scholars like Sato M, Watanabe M, Patel JM, and De Girolamo L have infused new vitality into the field, driving deeper and broader research exploration. It is noteworthy that, although two Chinese scholars have entered the ranks of high-output authors, their ACPP is relatively lower. This suggests potential room for improvement in the international recognition and citation rates of their research outputs, possibly related to factors such as research quality and dissemination strategies. Therefore, it is recommended to enhance support for key domestic researchers in the future, focusing on the cultivation of research talent and the elevation of research quality, to achieve higher levels of scientific breakthroughs and international influence in this field.

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Fig. 6 (A) Time overlay of author's cooperative networks. (B) Author co-citation network knowledge map.

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Fig. 6B provides a profound illustration of the intricate co-citation network among scholars with citation frequencies of 50 or more. In this figure, node size visually represents the number of citations received by the scholars, while the presence of connecting lines between nodes indicates shared citations of their academic work.¹⁶ The color variations of the nodes cleverly delineate their respective academic clusters.^17,18 According to the data presented in Table 4, Koh YG leads with an outstanding 210 citations, followed by Hunter DJ and Brittberg M, who have 155 and 148 citations respectively, underscoring their significant academic impact. This ranking not only highlights the leadership of these scholars within their respective fields but also emphasizes the substantial contribution and value of their research outputs to the academic community. Notably, Koh YG boasts the highest TLS, indicating his pivotal role in establishing an academic community. He has formed close and extensive co-citation connections with several distinguished scholars, including Kim YS, Jo CH, Saw KY, Wakitani S, Orozco L, Brittberg M, Vega A, and Emadedin M, further consolidating the breadth and depth of his academic network. It is noteworthy that, despite China's significant role in global research output, no Chinese scholars appear in this high-frequency citation list. This absence reflects a need for increased international influence and recognition among Chinese scholars. This phenomenon suggests that while pursuing the quantity of research output, there should be a stronger focus on enhancing research quality. By producing innovative and impactful research, Chinese scholars can bolster their presence and influence on the global academic stage, thereby fostering continued prosperity and advancement in their respective fields.

3.4 Analysis of journals

This study conducts a comprehensive analysis of the literature distributed across 267 academic journals, revealing that Osteoarthritis Cartilage stands out with a significant lead in publication volume, contributing 37 articles, which constitutes 5.43 % of the total corpus. This prominence underscores its central position in the field. Following closely is Am J Sport Med, which has published 30 articles, representing 4.40 % of the total, thereby demonstrating substantial academic impact. Int J Mol Sci ranks third with 25 articles, accounting for 3.67 %, thereby further enriching the diversity of the literature. For detailed data, refer to Table 5. It is noteworthy that Osteoarthritis Cartilage not only leads in publication output but also boasts a leading impact factor (IF), highlighting its authoritative status within the academic community. Meanwhile, the Am J Sport Med excels across multiple metrics, including TC, ACPP, and the H-index, reflecting its profound scholarly contribution and broad recognition within the field. The average H-index of these top ten high-output journals is 120.8, with an average IF of 3.72, and all are classified as Q1 or Q2 in the Journal Citation Reports (JCR). This underscores the high quality and extensive dissemination of research findings in this domain. Additionally, a notable feature is that these high-output journals predominantly originate from the United States and Europe, with American journals comprising 60 % of the total. This observation underscores the indispensable role of the United States and Europe, particularly the United States, in advancing knowledge dissemination and academic exchange in this field, with their journal platforms serving as vital avenues for global scholars to share their latest research findings.

Fig. 7 meticulously delineates a complex network of co-citations, focusing on journals cited at least 150 times, and further elucidates the academic interconnections among them. Table 6 distills the core data of the top ten most influential high-citation journals in the field, profoundly revealing their exceptional standing within the academic community. Notably, Osteoarthritis Cartilage, with an impressive citation count of 3,333, firmly maintains its position at the forefront, underscoring its indisputable influence. Following closely are Am J Sport Med and Arthritis Rheum-US, with citation frequencies of 1897 and 1,348, respectively, reflecting their substantial scholarly impact and widespread recognition within the discipline. Remarkably, Osteoarthritis Cartilage not only leads in citation frequency but also excels with the highest TLS value, vividly illustrating its central role in the academic interaction network with numerous prominent journals, including Arthritis Rheum-US, Ann Rheum Dis, Arthritis Res Ther, Am J Sport Med, J Orthop Res, J Bone Joint Surg Am, Arthroscopy, Knee Surg Sport Tr A, and Clin Orthop Relat R. This journal stands as a pivotal node in scholarly communication within the field. Additionally, although Arthritis Rheum-US ranks sixth in citation frequency, it leads in IF, further affirming its prestigious status as a high-quality academic journal. It is noteworthy that all ten leading journals originate from either the United States or Europe, with American journals constituting a significant portion. This phenomenon highlights the crucial role of the United States and European regions, particularly the United States, in advancing knowledge dissemination and academic innovation in this discipline.

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Fig. 7 Journal co-citation network knowledge map.

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Fig. 8 visually represents the intricate citation network architecture between citing and cited journals. The left side of the figure clearly lists journals that serve as sources of citations, while the right side displays the journals frequently cited.^19–21 The figure delineates six prominent citation pathways with vibrant lines, illustrating how research findings from journals in fields such as molecular/biology/genetics, as well as sports/rehabilitation/sport, have become indispensable sources of citations in literature from journals in molecular/biology/immunology, medicine/clinical/healthcare, and neurology/ophthalmology/sports. This analysis offers significant insights for researchers in the academic community: when pursuing the forefront of knowledge within a specific field, a strategic approach is to focus on journals with high citation frequencies and substantial impact. Moreover, when selecting suitable journals for manuscript submission, preference should be given to those that are actively publishing and making notable contributions. This strategy not only optimizes the submission process but also accelerates the recognition and publication of research outcomes, thereby facilitating the rapid advancement of scholarly communication.

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Fig. 8 Journal dual-map overlay.

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3.5 Analysis of subject categories

This study spans a broad range of interdisciplinary fields, encompassing a total of 68 distinct categories. Fig. 9 provides a visual representation of the interdisciplinary interaction network, highlighting categories that appear at least five times or more. The size of the nodes directly reflects the frequency of each discipline's occurrence, while the connecting lines symbolize their close relationships and shared research trends.²² The shading of the nodes subtly indicates the temporal evolution of these disciplines.^23,24 Notably, nodes encircled by a purple halo, with a betweenness centrality (BC) of at least 0.1, occupy a central position in the network and are crucial to its connectivity.^25,26 Further analysis of the data in Table 7 reveals that Orthopedics stands out with an impressive occurrence frequency of 247 times, representing a substantial 36.22 % of the field, thus becoming the most active research focus. This is followed by Sport Sciences and Rheumatology, with frequencies of 109 (15.98 %) and 96 (14.08 %) respectively, forming the foundational pillars of the research domain. When exploring the bridging roles between disciplines, Biochemistry and Molecular Biology leads with a BC score of 1.00, underscoring its irreplaceable role in facilitating interdisciplinary integration. Polymer Science and Engineering Biomedical follow with BC scores of 0.68 and 0.61, respectively, playing pivotal roles in constructing the interdisciplinary research network. Future research strategies should therefore emphasize enhancing these interdisciplinary synergies, aiming not only to broaden the scope of research but also to deepen its layers. By strengthening collaboration and communication across different disciplines, we anticipate advancing the field towards higher quality and more innovative research directions, ultimately contributing more robustly to human health and well-being.

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Fig. 9 Category co-occurrence network knowledge map.

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3.6 Analysis of highly cited references

In the academic realm, frequently cited works are often regarded as seminal contributions within their respective fields. They not only encapsulate core knowledge but also significantly influence subsequent research directions.^27,28Fig. 10 visually presents the intricate co-citation network of literature cited 20 times or more, while Table 8 highlights the top ten influential works, further affirming their exceptional research quality and academic value. These works are all positioned in the Q1 or Q2 quartiles of the JCR, underscoring their distinguished academic status. Foremost among these is the study by Jo CH et al.,²⁹ published in 2014 in Stem Cells, which evaluates the safety and efficacy of autologous adipose-derived mesenchymal stem cells (MSCs) for the treatment of KOA. This research demonstrates that injecting 1.0 × 10⁸ autologous adipose MSCs into the knee significantly improves knee function, alleviates pain, and promotes the regeneration of hyaline cartilage without adverse effects, effectively addressing cartilage defects. Following closely is the pioneering work by Brittberg M et al.,³⁰ published in New Engl J Med in 1994, which validated the effectiveness of autologous chondrocyte implantation in repairing deep cartilage defects of the knee joint through a long-term (average 39 months) follow-up of 23 patients with severe cartilage loss. The 2015 study by Vega A et al.,³¹ published in Transplantation, explores an alternative approach through a randomized, controlled trial assessing the potential and safety of allogeneic MSCs for osteoarthritis treatment. The findings reveal that this therapy is not only efficient and convenient but also effectively alleviates pain and improves cartilage quality, providing a new treatment option for patients with chronic KOA. Additionally, Kellgren JH et al.,³² in their 1957 study published in Ann Rheum Dis, delves into the subjective differences in X-ray interpretation for osteoarthritis assessment, emphasizing the importance of standardized reading processes. Davatchi F et al.,³³ in their 2011 study in Int J Rheum Dis, preliminarily explored the potential of bone marrow MSCs transplantation in reversing the progression of KOA through a small-scale clinical trial. Koh YG et al.^34,35 conducted studies in 2012 (Knee) and 2013 (Arthroscopy) focusing on the application of MSCs derived from the infrapatellar fat pad in treating KOA, demonstrating the safety and efficacy of intra-articular injection therapies, which provide significant pain relief and functional improvement for patients. Orozco L et al.,³⁶ in their 2013 publication in Transplantation, presented a non-surgical, minimally invasive treatment option for chronic knee pain through intra-articular injection of autologous bone marrow MSCs, reiterating the substantial potential of MSCs in regenerative medicine. Wakitani S et al.,³⁷ in their 2002 study published in Osteoarthritis Cartilage, concentrated on the use of autologous cultured bone marrow MSCs for repairing cartilage defects in KOA, further consolidating MSCs' role in cartilage regeneration. Lastly, the 2006 paper by Dominici M et al.,³⁸ published in Cytotherapy, provided critical standardization for mesenchymal stromal cells, defining their biological characteristics, surface markers, and differentiation potentials, laying a solid foundation for further research and broad applications of this cell type.

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Fig. 10 Reference co-citation network knowledge map.

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Collectively, although substantial progress has been registered in the application of MSCs for cartilage regeneration in KOA, several critical obstacles remain. First, pronounced inter-source heterogeneity in proliferative capacity, chondrogenic efficiency, and immunogenicity of MSCs precludes the establishment of a uniform cell-manufacturing protocol and thus compromises both reproducibility and scalable deployment of MSC-based therapies. Second, the majority of current investigations remain confined to efficacy validation—pain reduction and cartilage defect repair—whereas mechanistic insights are largely restricted to the macroscopic concept of paracrine signaling. This mechanistic black box precludes precise patient stratification and hampers the rational genetic engineering of MSCs for enhanced potency. Third, under the emerging paradigm of personalized medicine, a patient-cell-dose matching framework is urgently required; however, existing datasets have yet to integrate radiographic, molecular biomarker, and cellular phenotypic information, thereby obstructing the development of on-demand therapeutic regimens. Finally, the convergence of biomaterials science and regenerative medicine has popularized“MSC + scaffold” strategies in which materials such as hyaluronic acid and collagen provide three-dimensional microenvironments that promote engraftment and chondrogenesis. Nevertheless, most studies have explored only single scaffold–MSC combinations without dissecting the synergistic relationship between scaffold properties (pore size, degradation kinetics) and MSC functionality. These challenges constitute the principal bottlenecks impeding the transition of MSC therapy from bench to bedside. Future investigations must therefore be driven by unmet clinical needs and leverage single-cell multi-omics, artificial intelligence, and gene-editing technologies. A tripartite framework—source standardization, manufacturing harmonization, and mechanistic precision—should be implemented to ensure therapeutic uniformity, while multi-technology integration (MSC + intelligent scaffold + predictive efficacy model) should enable precision therapy, ultimately propelling MSCs from a niche intervention to a broadly applicable clinical modality for patients with degenerative joint disease.

3.7 Analysis of references burst

The phenomenon of references bursts, characterized by a significant increase in citation frequency within a specific time period, serves as a crucial indicator of research hotspots and emerging trends.^39–41 This study establishes a minimum burst duration of five years and identifies a collection of the top thirty documents exhibiting the highest burst intensities, as detailed in Fig. 11. In the figure, the "Strength" metric measures the degree of the burst, with higher values indicating more pronounced bursts; the "Begin" and "End" markers delineate the initiation and cessation years of the bursts, respectively.^42–44 The blue bars represent the time span, while the red bars highlight the duration of the burst.^45–47 Notably, nine documents have continued burst activities into 2023 or later, reflecting current research hotspots and suggesting future directions, thus becoming the focal point of our analysis. Among these nine documents, the leading study is by Jo CH et al.,²⁹ published in 2014 in Stem Cells. This study not only stands out for its peak burst intensity but also leads in citation count, as previously discussed. Following closely is the work by Vega A et al.,³¹ published in 2015 in Transplantation, which ranks high both in burst intensity and citation rate, also elaborated upon earlier. The third-highest burst intensity is observed in the study by Gupta PK et al.,⁴⁸ published in 2016 in Arthritis Res Ther. This research focuses on the in vitro differentiation potential of adult bone marrow-derived mesenchymal stromal cells (Stempeucel®) in cartilage formation, evaluating it through quantitative sulfated glycosaminoglycans and exploring its potential in treating KOA, initially proving the safety and potential efficacy of intra-articular injection while emphasizing the need for further clinical validation. The fourth highest burst intensity is associated with the study by Pers YM et al.,⁴⁹ published in 2016 in Stem Cell Transl Med, which investigates dose escalation strategies for adipose-derived stromal cells in the treatment of KOA. This study evaluates both safety and preliminary efficacy, showing that the therapy is safe and well-tolerated, offering new hope for treatment. In the same year, the research by Lamo-Espinosa JM et al.,⁵⁰ published in J Transl Med, ranks fifth. It explores the potential of combined treatment with bone marrow-derived mesenchymal stromal cells and hyaluronic acid, finding that a single high-dose intra-articular injection of autologous bone marrow-derived mesenchymal stromal cells combined with hyaluronic acid significantly improves clinical and functional outcomes for patients with KOA. The study by Vangsness CT Jr et al.,⁵¹ published in 2014 in J Bone Joint Surg Am, ranks sixth in burst intensity. This research delves into the safety of intra-articular injection of human MSCs and their role in promoting meniscal regeneration, as well as their effects on KOA symptoms, yielding positive results and providing new perspectives for clinical treatment. Additionally, the 2017 study by Jo CH et al.,⁵² published in Am J Sports Med, ranks seventh. It further confirms the mid-term safety and efficacy of autologous adipose-derived MSCs in treating KOA over a two-year follow-up, while also highlighting the need for more research on long-term efficacy. The eighth-highest burst intensity is observed in the 2005 study by Sakaguchi Y et al.,⁵³ published in Arthritis Rheum. This study provides a comprehensive comparison of MSCs from different tissue sources, emphasizing the unique advantages of synovial-derived MSCs in clinical applications. Lastly, the research by Davatchi F et al.,⁵⁴ published in 2016 in Int J Rheum Dis, ranks ninth in burst intensity. This longitudinal study, spanning five years, assesses the long-term effects of MSCs therapy for KOA, revealing the positive impact of early transplantation on long-term prognosis. In summary, these documents offer an in-depth exploration of the application of MSCs from various sources in the treatment of KOA, examining aspects such as safety, efficacy, and long-term outcomes, and providing a wealth of data and insights for research in this field.

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Fig. 11 References burst map.

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Accordingly, future research directions should be prioritized in the following areas to address current gaps and advance translational applications in cartilage regeneration. First, the exploration of alternative stem cell types warrants systematic investigation. Focus should be placed on induced pluripotent stem cells (iPSCs), given their unlimited proliferative capacity and multipotent differentiation potential. Genetic engineering approaches could be employed to optimize chondrogenic differentiation efficiency. Additionally, easily accessible stem cell sources with minimal ethical concerns, such as dental pulp stem cells (DPSCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), should be evaluated. Comparative analyses are recommended to assess differences in chondrorepair capacity, anti-inflammatory efficacy, and in vivo survival duration between these cell types and conventional bone marrow-derived MSCs. Such studies would facilitate the establishment of patient selection criteria based on cell-type specific therapeutic profiles. Second, enhanced integration of tissue engineering strategies is critical. Bioactive scaffold systems with biomimetic architectures should be developed using biocompatible materials including polycaprolactone, hyaluronic acid, and collagen. Three-dimensional bioprinting technologies could enable precise fabrication of scaffolds with cartilage-mimetic microstructures and biomechanical properties. Co-culturing stem cells with these scaffolds in bioreactor systems may create synergistic "cell-scaffold-growth factor" constructs, thereby improving cartilage repair integrity and long-term stability upon implantation.

Third, combinatorial approaches combining gene therapy and stem cell therapy should be investigated. Genetic modulation targeting chondrogenic master regulators (e.g., SOX9, COL2A1) could be achieved through viral vectors (lentivirus, adeno-associated virus) to enhance in vivo chondrogenesis and matrix synthesis. Dose-response and temporal kinetics studies are essential to optimize gene delivery parameters while mitigating risks of dysexpression-induced cellular dysfunction. Finally, methodological refinements in preclinical and clinical research design are required. Multi-center, large-scale randomized controlled trials with extended follow-up periods (≥5 years) should be implemented. Stratified analysis based on patient demographics (age, disease stage, lesion severity) would clarify treatment indication boundaries. Safety endpoints should include monitoring for ectopic calcification/ossification, while efficacy assessment should incorporate both conventional metrics (WOMAC, VAS scores; MRI/X-ray imaging) and novel biomarkers (serum/synovial CTX-II, IL-6 levels). Patient-reported outcome measures (PROMs) should be integrated to comprehensively evaluate quality-of-life improvements.

3.8 Analysis of keywords

In delving into the research dynamics of a specific academic field, the analysis of high-frequency keywords serves as a crucial distillation of the essence of research themes.^55,56 Such analysis is pivotal for grasping the core content and emerging hotspots within the field.^57,58Fig. 12 visually presents a co-occurrence network of keywords that appear at least 20 times, while Table 9 provides a detailed enumeration of the top 20 high-frequency keywords in the domain. These terms not only reflect the breadth and depth of research but also unveil core issues. Notably, keywords such as platelet rich plasma, intraarticular injection, hyaluronic acid, inflammation, regenerative medicine, cartilage regeneration, tissue engineering, management, and efficacy are particularly prominent, indicated by their red nodes in the figure. This prominence suggests that these keywords are currently at the forefront of research, reflecting contemporary research trends. Further, Fig. 13 employs the log-likelihood ratio algorithm to cluster keywords into 23 significantly meaningful labels, and the dynamic evolution of these clusters over time is clearly depicted through a timeline map.⁵⁹ The high quality of clustering is corroborated by metrics such as modularity Q = 0.8592 and weighted mean silhouette S = 0.94, both indicating that the clustering structure is both significant and robust.^60–62 Of particular note is the sustained presence of clusters #5 high tibial osteotomy and #9 platelet rich plasma, which underscores the stability and continuity of recent research focuses. To accurately capture the dynamic changes in research hotspots, we established a threshold of a 2-year burst duration for keywords and identified 30 keywords with high burst intensities (see Fig. 14). The burst activities of these keywords not only reveal the focal points of research during specific periods but also serve as indicators for recent and future research priorities. Specifically, keywords such as management, stem cells, tissue, efficacy, cartilage regeneration, inflammation, extracellular vesicles, regenerative medicine, exosome, and intraarticular injection exhibit burst activities extending into 2023 and beyond, signaling their prominence not only in current research but also as likely leaders in future research directions and trends. In summary, a thorough analysis of keywords enables us not only to discern the accumulation of past research but also to anticipate and guide future scientific trends.

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Fig. 12 Keyword co-occurrence network time overlay map.

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Fig. 13 Keyword timeline map.

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Fig. 14 Keywords burst map.

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3.9 Strengths and limitations

Through the application of bibliometric methodologies, we have conducted a comprehensive and in-depth review and analysis of the application of cartilage regeneration and repair techniques in the field of KOA. Utilizing advanced visualization techniques, we present the essence of the research findings in a clear and intuitive manner. Compared to traditional literature reviews or meta-analyses, this study significantly enhances the breadth of literature coverage and the meticulous handling of data, effectively mitigating the influence of subjective bias on the research outcomes and ensuring the objectivity and reliability of the conclusions. However, it is important to acknowledge several limitations of this study. Firstly, the data source is predominantly restricted to the SCI-Expanded subset of the well-recognized WoSCC database,^63–66 with specific criteria for literature type and language. While this approach aims to enhance data quality and research rigor, it may inevitably result in the exclusion of some relevant studies that meet the criteria, potentially leading to information loss. Nonetheless, this measure ensures a high standard for the analytical foundation and helps concentrate on high-quality research outcomes. Secondly, given that academic impact is often correlated with the cumulative citation count over time, some recent outstanding studies may not yet fully reflect their academic value due to their relatively low citation counts. This limitation affects our ability to comprehensively grasp the latest advancements in research. Additionally, as data for the year 2024 remains incomplete, it was not included in our analysis, which somewhat restricts the timeliness of the study. Despite these limitations, our findings provide significant reference value and guidance, offering valuable insights and inspiration to experts and scholars in the field. The research contributes to the advancement and further exploration of cartilage regeneration and repair techniques in the treatment of KOA.