The Web of Science database core dataset was searched.The search results show that the earliest research in this field appeared in 2003, so the search period starts from 2003, the articles were well-representative and peer-reviewed journal papers. Add search terms to the basic search, select “Article” and “Review” for the document type, “English” for the language, and the search period was selected from 2003 to 01–01 to 2022–09–25. The search formula “TS = (Platelet Rich Plasma OR Platelet-Rich Plasma AND Tendon OR Ligament OR Tendinopathy)” was used in the advanced search section to retrieve a total of 2040 relevant articles. A total of 1,827 documents were included after filtering and excluding conference abstracts, proofreading notices, news, conference papers, and retraction notices by the document types included in the Web of Science database. The retrieved literature records were exported in “plain text” format, including “complete records and references”, and a file was generated for every 500 records, renamed as “download”, and then imported into the “input” folder of citespace software, and finally start the visual analysis. The workflow diagram is shown in Figure 1.

Two reviewers independently read the literature. Articles were initially screened by title and abstract before inclusion and exclusion criteria were applied. During screening, if a dispute arises, a third reviewer is assigned to read the entire paper and make a decision.

CiteSpace 6.1 identifies the information relationship in literature based on relevant information in articles. According to the parameters setting for CiteSpace 6.1 visualization software, 2003–2022 is the period, one year is the time division, the threshold item is selected as “Top N” and set to 50, then select “Pathfinder” as a cut link to simplify the network structure and highlight key features. For the node type, country (region), institution, author, journal, cited author, keyword, and cited literature are selected for co-occurrence analysis and visualization mapping (12). The visualization was done. We also use CiteSpace to explore the rate of change of keywords and key literature proliferation by using the CiteSpace prominence detection function and generate the ranking table of keywords and key literature with high-intensity mutation rates to analyze the current situation and predict prospects (13). The keyword and key literature ranking table are generated to analyze the current status and predict prospects.

In this paper, three scientometric software and Microsoft Excel programs were used to perform the bibliometric analysis: CiteSpace version 6.1R3, VOSviewer version 1.6.18, and the R-Studio-based visualization software R-bibliometrix version 4.6.1. Citespace and VOSviewer were mainly used to visualize and analyze the knowledge structure and evolutionary trends of the scientific literature in a given field (14). In addition, sub-clusters can be extracted from the overall structure of the literature network through cluster analysis to identify research sub-domains, i.e., research hotspots (15). Identification of research frontiers through overlap analysis using R-bibliometrix, VOSviewer, and CiteSpace software can largely predict the research directions that may yield major breakthroughs in the coming years. Through an in-depth review of the results, researchers can quickly grasp the knowledge base and trends in the field to improve their research results and adjust their research strategies.

The Web of Science database is one of the largest citation databases in the world, and the accessibility of this study was obtained through the library of the University of Science and Technology of China. A total of 1,827 papers on using platelet-rich plasma to treat ligament and tendon injuries were retrieved, and Figure 2A shows the annual publication volume in different countries. The number of research papers on using platelet-rich plasma to treat ligament and tendon injuries generally maintained a gradually increasing trend from 2003 to 2022, and in 2010 the field began to grow by leaps and bounds, with nearly three times the number of papers published in 2009. The United States accounts for the largest number of publications per year, followed by China, especially in recent years, with a significant increase year by year.

We discovered substantial connections between the number of publications and the year of publication using a polynomial fit analysis (coefficients of determination (R2) of 0.9432, 0.8844, 0.9835, and 0.7456 for total papers, articles, reviews, and randomized controlled trials, respectively). According to the polynomial fit study, we forecast that there will be around 222 published publications in 2025, comprising of 110 articles, 109 reviews, and 30 randomized controlled trials, as shown in Figure 2B. Overall, the boom in this field in orthopedics and sports medicine has led to an increasing depth of research. However, it can be observed that despite the yearly increase in the number of publications, there still needs to be more high-quality RCT studies.

A total of 68 countries or regions were included in the obtained visualization, among which 14 countries or regions have ≥ 50 articles and the highest number of articles is United States with 678 articles, the second is China with 187 articles, and the third is Italy with 172 articles. The visualization of research countries suggests that the top 3 nations in terms of centrality are United States (0.27), ENGLAND (0.19), and SWITZERLAND (0.17). The graph demonstrates that these 3 nations have had successful research partnerships with other nations, see Figure 2C, Table 1.

Using platelet-rich plasma to treat ligament and tendon injuries is a hot spot for institutional collaborative research. A total of 1,684 nodes, 3,707 connections, and a topological network density of 0.0026 were generated. 1,684 institutions published research on using platelet-rich plasma to treat ligament and tendon injuries, with 14 institutions publishing ≥ 20 articles, the most prolific being Hosp Special Surg (New York Hospital for Special Surgery) with 56 articles, the second being Stanford Univ (Stanford University) with 43 articles, and the third being Univ Pittsburgh (University of Pittsburgh) with 43 articles. Univ Pittsburgh (University of Pittsburgh) with 43 articles; the top 3 institutions in terms of centrality, as suggested by the visualization of research institutions, were Univ Pittsburgh (0.2), Hosp Special Surg (0.13), and Univ Milan (0.13). These three institutions have well-established research collaborations with other institutions. See Figure 2D, Table 1.

The most prominent author was Maffulli N, University of Salerno, Italy (48 articles); the second most frequent author was Murray M, Harvard Medical School, United States (42 articles); the third most frequent author was Andia I, University of Cruces, Spain (34 articles); the highest document centrality was achieved by Zhang J, University of Pittsburgh, United States and Su CA, Case Western Reserve University, United States, both with 0.07 centrality. The highest cited authors are Anitua E of the Eduardo Anitua Institute of Biomedical Research, Spain (478 citations), followed by Mishra A of Stanford University, United States (390 citations) and Anton Anton, The Netherlands. (390 times) and de Vos RJ, Antoniushove Medical Center, The Hague, The Netherlands (389 times). Among the highly prolific posting authors, the research team represented by Italian scholars Maffulli N, Denaro V, and Longo UG has a strong collaborative relationship and forms a research group with a dense aggregation. The results of the members of this team regarding this study are focused on clinical studies and experimental animal models of platelet-rich plasma on tendinopathy; the research team centered on Murray M, Vavken P and Fleming B from Harvard Medical School, United States, whose research area is collagen-platelet-rich plasma hydrocoagulation scaffold promotion on histological repair of central anterior cruciate ligament wounds The research team is centered on Andia I, Sanchez M and Anitua E from the University of Cruces, Spain, whose members are working on the in vitro cellular molecular biology of growth factor (PRGF)-rich preparations on tendon cells, the molecular biology of platelets in healing and tissue regeneration and their potential impact on different disciplines; and the research team is centered on Wang J, Zhang J and Zhang Y of the University of Pittsburgh, United States, the research team whose members' research area is the cellular molecular biology of platelet-rich plasma release agents promoting the differentiation of tendon stem cells into live nature cells. The figure shows that there is some author team collaboration, however it is more pronounced among the high-yield authors and there aren't many authors who are high centrality to the literature, see Figure 3A–C, Table 2.

The distribution of research hotspots in the literature was analyzed, and 25 categories were created from the 1,827 documents that were successfully recovered. Among them, 711 were in the orthopedic category, 534 in the sports science category, and 321 in the surgery category. From the data, it can be seen that using platelet-rich plasma to treat ligament and tendon injuries has been extensively researched and developed in orthopedics, sports science, and surgery, Figure 3D.

The top three journals in terms of the number of articles were AMERICAN JOURNAL OF SPORTS MEDICINE (121 articles, total citations 3854, average citations 31.85), ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY (71 articles, total citations 1119, average citations 15.76) and KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY (53 articles, total citations 484, average citations 9.13). (53 citations, 484 total citations, 9.13 average citations). The top three journals with high H-index for using platelet-rich plasma to treat ligament and tendon injuries were AMERICAN JOURNAL OF SPORTS MEDICINE (16), ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY (17), and JOURNAL OF ORTHOPAEDIC RESEARCH (18); based on the co-citation analysis of journals produced by VOSviewer, platelet-rich plasma The top three cited research studies for the treatment of tendon and ligament injuries were AMERICAN JOURNAL OF SPORTS MEDICINE (1090), JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME (849), and JOURNAL OF ORTHOPAEDIC RESEARCH (770) Figure 4A,B, Table 3. currently, the impact of journals publishing in this research area is high.

The biplot overlay's colored paths connecting journal groups depict the citation relationships between the citing and cited journals, illuminating the knowledge flow and citation trajectory (19). The colored paths indicate that studies published in pharmaceutical/medical/clinical journals typically cite studies published in sports/rehabilitation/exercise, health/nursing/medicine, molecular/biology/genetics, and veterinary/zoology/quarantine.More information about representative citations and cited journals in each cluster can be found in Figure 4C. For instance, the American Journal of Sports Medicine, Arthroscopy, Journal of Bone and Joint Surgery American Volume, Journal of Orthoptera Research, and British Journal of Sports Medicine are the most typical journals in the Sports/Rehab/Exercise cluster.

Keyword analysis plays a key role in summarizing research hotspots and exploring research trends (14). After removing the subject terms related to the search strategy, a topological network density of 0.0094 was developed, resulting in a total of 481 nodes and 1,084 connections, and the keywords with higher co-occurrence are represented in Figure 5A,B, Table 4. The research hotspots at that time are represented by keywords with a higher centrality and frequency. Analysis of popular keywords revealed that research in this field focused on growth factor, mesenchymal stem cell, repair, randomized controlled trial, double blind, injection, in vitro, stem cell, corticosteroid injection, anterior cruciate ligament, rotator cuff repair, proliferation, lateral epicondylitis, injury, management, achilles tendon, and follow up. Figure 5C exhibits the keyword co-occurrence clustering map in this domain. Using the classical LLR algorithm, a total of 13 clusters were formed, and the keyword clustering analysis showed that the homogeneity between research was greater the higher the degree of aggregation (20). The higher the degree of aggregation, the better the homogeneity among studies. The cluster number is inversely proportional to the cluster size, with the largest cluster marked by #0 and so on. The keyword clusters from #0 to #12 were tennis elbow, in vitro, tissue engineering, rotator cuff, platelet-rich plasma, reconstruction, wound healing, cell, growth factor, follow up, achilles tendon, suture repair, and guided tissue regeneration. The clusters #0, #2, #3, #7, #8, #9, and #10 are most intersectingly linked, followed by #2, #9, and #11 intersectingly linked, and #4, #12 intersectingly linked. Keyword co-occurrence and cluster analysis yielded that tennis elbow, in vitro, anterior cruciate ligament, rotator cuff repair, mesenchymal stem cell, growth factor, follow up, achilles tendon, suture repair, and guided tissue regeneration are current research hotspots in this field.

A timeline view of the literature that the Web of Science database has filtered reveals the temporal dynamics of the clustered keywords, Figure 6. Cluster modularity (Q value) = 0.6433 > 0.5, indicating significant cluster structure; cluster Silhouette (S value) = 0.8587 > 0.5, indicating convincing clustering (21). From 2003 to 2005, the keywords repair, expression, growth factor, differentiation, extracellular matrix, cell, platelet-rich plasma, ligament, in vitro, matrix, cruciate ligament reconstruction, plasma-rich, endothelial growth factor, gel, growth factor beta, guided tissue regeneration, proliferation and regenerative medicine received extensive attention; from 2005 to 2010, the keywords treatment, tendinopathy, achilles tendinopathy, gene expression, stem cells, anterior cruciate ligament, tissue engineering, rotator cuff repair, tear, efficacy, tendon repair, surgical treatment, sports medicine, jumpers knee, patellar tendon, in vivo, patellar tendinopathy, reconstruction, graft, mesenchymal stem cells, tendon, platelet-rich plasma, follow up, achilles tendon and injury began to receive attention; 2010 to 2015 chronic achilles tendinopathy, injection, lateral epicondylitis, double blind, tennis elbow, randomized controlled trial, management, corticosteroid injection, hyaluronic acid, pain, stromal cells, fibrin matrix, arthroscopic repair, rotator cuff and anterior cruciate ligament reconstruction are getting attention; 2015 to 2020 intra-articular injection, rotator cuff tear, clinical outcome, meta-analysis, conservative treatment and muscle are getting attention; 2020 to 2022 centrifugal motion, progenitor cells, sodium hyaluronate, platelet-rich fibrin, physical therapy, greater trochanteric pain syndrome, classification, and partial meniscectomy are new terms. It is predicted that using platelet-rich plasma to treat ligament and tendon injuries will continue to be studied in depth around centrifugal exercise therapy, sodium hyaluronate, physical therapy, platelet-rich fibrin for external epicondylitis, ex vivo injection of progenitor cells and mesenchymal stem cells for rotator cuff tears, and classification and follow up related to growth factors.

Among the 20 mutation words with the highest frequency of cited literature screened by the Web of Science database, mutation words represent keywords that are frequently cited during a certain period of time, such that hotspots and trends can be identified. There are 8 mutation words with a mutation period from 2017 to 2022. The strongest mutation was “growth factor beta” (13.98), followed by “efficacy” (13.78), and in third place was “guided tissue regeneration” (13.08). The keywords with high mutation intensity in the past 5 years include: “outcm” (2017–2022), “rotator cuff tear” (2017–2022), patellar tendinopathy” (2018–2020). Figure 7A. Combining the temporal dynamics of the keywords and Burst analysis, it is possible to form a general picture of the development and future research trends in the field of using platelet-rich plasma to treat ligament and tendon injuries. “outcm”, “rotator cuff tear”, “efficacy”, “pain”, “ hyaluronic acid” and “intraarticular injection” all continue to be studied to this day and are likely to remain so.

A total of 1,827 papers were retrieved in this field, with a total citation frequency of 8,136, and the co-citation graph of research literature generated 1,131 nodes and 3,594 connections, with a topological network density of 0.0056. The top 10 rankings of literature with high citation frequency and high centrality are shown in Figure 7B, Tables 5, 6. One of the key markers of the research hotspots is the citation situation and centrality, and by studying the literature that has a lot of citations and centrality. It is possible to comprehend some research findings carefully in order to identify the areas of interest in the field. The top 10 documents with high citation and centrality were read and analyzed.

The key node literature is usually the literature that presents significant theoretical or innovative concepts in the field and is also the literature that is most likely to generate new research hotspots. Based on the analysis of the co-citations of the key nodes and the most frequently cited literature, we can sort out the research hotspots and evolutionary trajectory of platelet-rich plasma in the field of tendon ligament injury treatment. These 20 pieces of literature are the most important classical literature in the study and can represent the key research contents in the field. Based on the classification of research objects, they can be divided into 3 categories: clinical studies, in vitro experimental studies and reviews. The 1st, 2nd, 6th centrality and 1st, 2nd, 3rd, 4th, 5th, 8th, 9th, and 10th citation frequency are clinical studies, the 4th, 9th centrality and 7th citation frequency are in vitro experimental studies, and the 3rd, 5th, 7th, 8th, 10th centrality and 6th citation frequency are review studies. The highly cited literature in clinical studies involved achilles tendinopathy (centrality 1, 2 and cited frequency 1, 5 studies), humeral epicondylitis (centrality 3, 6 and cited frequency 2, 9 studies), rotator cuff tears (cited frequency 3, 4, 8 studies), patellar tendinitis (cited frequency 10 studies) and anterior cruciate ligament tears (centrality 4 studies), respectively. According to research, tennis elbow, rotator cuff tendon damage, achilles tendon tendinopathy, and patellar tendinopathy had the highest prevalence of various tendinopathies (37). The results of the study were consistent with the highly cited literature. The research methods used in the literature were double-blind, randomized controlled method (centrality 6th and cited frequency 2nd and 9th studies) and experimental method (centrality 1st, 2nd and cited frequency 1st, 3rd, 4th, 5th, 8th and 10th studies), and for the assessment of treatment outcomes, most of them used visual analog rating scale as a test indicator, as shown in Table 7 which examines the clinical treatment of tendon ligament injuries in the above mentioned 20 significant literature The additional bioactive compounds, doses, therapies and clinical outcomes of the studies are summarized. The effectiveness of platelet-rich plasma in the treatment of tendon ligament injuries was illustrated by comparing the changes in the values of the visual analog scale through a certain period of follow up. By using platelet-rich plasma for the treatment of different tendinopathies, the results of all clinical studies showed that the use of platelet-rich plasma and its related agents had a better effect on tendon and ligament injuries in terms of long-term prognosis, with significant differences in visual analog score scale values before and after treatment. However, in the study with the 1st literature centrality and 1st citation frequency, the authors found that although there was a significant change in the visual analog score values during the follow up period after the use of platelet-rich plasma, no significant difference was observed when compared with other controls.

Notably, in the 2nd most cited study, the investigators compared autologous platelet-rich plasma with corticosteroid injections for the first time as a treatment option for patients with failed nonsurgical treatment of humeral epicondylitis to investigate the efficacy of platelet-rich plasma vs. corticosteroids in the treatment of chronic epicondylitis. Prior to the publication of this study, corticosteroid injections for tendinopathy had been used as the gold standard for the treatment of epicondylitis, and while this treatment had good short-term efficacy, adverse outcomes were often seen after 12 weeks of follow up (38). A single injection of platelet-rich plasma provided better improvements in pain and dysfunction than corticosteroid injections, and these improvements persisted over time. In addition, in the Cited Frequency 10 study, investigators used multiple injections of platelet-rich plasma as a treatment modality for patients with chronic jumper's knee disease who failed both nonsurgical or surgical treatment, exploring the efficacy of multiple consecutive platelet-rich plasma injections for chronic jumper's knee disease, after the vast majority of previous studies were single injections with little or late onset of treatment effects for chronic tendinopathy (22, 27). Successive PRP injections have shown satisfactory clinical results in difficult cases of chronic refractory tendinopathy after the failure of previous classical treatments. In all clinical trial studies involving rotator cuff tear repair, investigators have used platelet-rich fibrin matrix (PRFM) as an adjunct to repair. Autologous PRFM does not improve the healing of small to medium rotator cuff tears repaired with double-row anchor staples and may even have a negative effect. PRFM promotes pain reduction and recovery of external rotation strength in patients with complete rotator cuff tears repaired with single-row anchor staples.

In an in vitro experimental study, three papers selected complete tears of the anterior cruciate ligament in dogs (centrality study 4) and human tendon cells (centrality study 9 and cited frequency study 7) as subjects respectively. Repaired complete tears of the anterior cruciate ligament in dogs using collagen-PRP stent links, and measured fibronectin, fibrinogen, PDGF-A, TGF-b1, FGF-2, procollagen I, and vWF (revascularization markers) levels were measured in the ACL after a period of repair and compared with the repair of complete tears of the medial collateral ligament, with the aim of investigating whether collagen-PRP hydrogel could partially improve the repair as a temporary replacement scaffold at the ACL wound site. Platelet-rich plasma (centrality study #9), platelet-rich plasma clot releasers, and platelet-poor plasma clot releasers (cited frequency study #7) at different concentrations were selected as culture media for tendon or tendon cells. After a period of culture, the expression of type I collagen, type III collagen, cartilage oligomeric matrix proteins, matrix metalloproteinases, and the expression of proteins or protein genes related to tendon cell anabolism, such as vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor, were measured in tendon or tendon cells, with the aim of studying the cellular, molecular biology related to platelet-rich plasma on tendon cell synthesis.

Cluster analysis based on co-cited literature can present subfields that represent major research hotspots (39). Cluster modularity (Q value) = 0.8231 > 0.5, indicating significant cluster structure; cluster silhouette (S value) = 0.8681 > 0.5, indicating convincing clustering (21). The classical LLR algorithm was used. The classical LLR algorithm was used to form a total of 16 clusters, and the keyword clustering analysis showed that the homogeneity between research was greater the higher the degree of aggregation (20). The cluster number is inversely proportional to the cluster size, and the largest cluster is marked with #0, and so on, Figure 7C. The keyword clusters from #0 to #15 are network meta-analysis, achilles tendinopathy, articular cartilage avulsion, platelet-rich plasma therapy, different platelet-rich plasma concentration, pilot study, chronic patellar tendinosis, collagen hydrogel, musculoskeletal lesion, platelet concentrate graft, shoulder surgeon, new horizons, porcine anterior cruciate ligament, hgf production, lysophosphatidic acid, and connective tissue craft harvesting. In terms of the order of clustering, the top research trends in the field were literature review of network meta-analysis, achilles tendinopathy, different platelet-rich plasma concentrations, pilot studies, and chronic patellar tendinopathy; in terms of lighter colored clusters, the trends in the field were different platelet-rich plasma concentration, pilot study, articular cartilage avulsion, musculoskeletal lesion, and collagen hydrogel.

The citations represent key literature that has been frequently cited over a period of time, thus indicating hot spots and trends, Figure 7D. Among the 25 most frequently cited citations screened by the Web of Science database, the strongest mutation was found by de Vos RJ in 2010, who found that PRP injections did not lead to greater improvement in pain and activity compared to saline injections in patients with chronic achilles tendinopathy treated with centrifugal exercise (41.18), followed by Sanchez M in 2007, who found that the use of a platelet-rich fibrin matrix did not lead to greater improvement in pain and activity. In third place, de Mos M in 2008 found that platelet-rich clot releasers (PRCR) stimulated cell proliferation and total collagen production. Proliferation and total collagen production slightly increased the expression of matrix degrading enzymes and endogenous growth factors. Platelet-rich plasma was found to enhance tendon repair from a cell culture perspective (32.79). The literature can be broadly divided into four parts based on the emergence of the literature, the first part focusing on the in vitro cellular molecular biology of platelet-rich plasma and its preparations on tendon and ligament cells (2003–2014) (33, 40–42) The second part focuses on the comparative efficacy of platelet-rich plasma and its preparations on specific tendon and ligament injuries (chronic epicondylitis, rotator cuff repair, jumper's knee, chronic achilles tendinopathy) (based on intention-to-treat principles) and longer-term follow up studies (≥1 year) after treatment (2011–2016) (30, 35, 43); the third part focuses on a large sample size double-blind clinical randomized controlled study of the efficacy of platelet-rich plasma and its preparations in tendon injuries (2014–2019) (27, 44); Part IV focuses on a meta-analysis of the efficacy of platelet-rich plasma on tendon and ligament healing and an investigation of the efficacy of sequential multiple injections of PRP on tendon or ligament healing (2017-present) (18, 45) Based on a careful reading of the high-burst citations, it is possible to foresee future research trends exploring the efficacy of platelet-rich plasma and its preparations on tendon and ligament healing, longer follow up, network meta-analyses based on a large body of literature, studies on the efficacy of multiple consecutive injections of PRP on tendon or ligament healing, the role of PRP in acute, chronic and Severe tendon and ligament healing, comparative studies of the optimal concentration of PRP for injection time or residence time at the site of injury, studies of standardized doses and composition of PRP and formulations, and studies of the effects of injectable agents and injection site PH.

A two-dimensional matrix is used to illustrate the thematic maps created with the R-Bibliometrix software. The x-axis and y-axis, respectively, indicate the two dimensions of matrix centrality and density. The y-axis represents density, or the centrality of the subject, while the X-axis represents centrality, or the salience of the subject. Thus, the upper right quadrant refers to motor themes that are both important and well developed, the upper left quadrant refers to niche themes that have been well developed but are not important to the current field, the lower left quadrant refers to emerging or declining themes that are not well developed and may have just emerged and perhaps are about to disappear, and the lower right quadrant refers to basic topics that are important to the field but have not been well developed. It generally refers to the basic themes, Figure 8. One can find one keyword bubble for tendinopathy and lateral epicondylitis in the motor theme quadrant; two keyword bubbles for platelet lysate, proliferation, mesenchymal stromal cells and osteogenic differentiation, periodontal ligament stem cells in the niche theme quadrant; two keyword bubbles for clinical trials and achilles tendinopathy, plantar fasciitis, allografts in the emerging or declining theme quadrant; and two keyword bubbles of tissue engineering, regenerative medicine, stem cells, and platelet-rich plasma, growth factors, PRP in the basic theme quadrant; the keyword bubble of periodontal regeneration, platelet-rich fibrin, and guided tissue regeneration spanning both the motor theme and the niche theme; and the keyword bubble of tendon, horse, and ligament spanning both the motor theme and the basic theme. Based on the quadrant where the key bubbles are located, it can be speculated that tendinopathy, lateral epicondylitis, horses, guided tissue regeneration, and ligaments are the hotspots of research in this field; while achilles tendinopathy, plantar fasciitis, allograft, and clinical trial themes may be developed or disappear in the future, while in the direction of tissue engineering, regenerative medicine, horses, stem cells and platelet-rich plasma, growth factors, and PRP themes need to be more in-depth research.

Since its discovery, platelet-rich plasma has been widely used in the fields of dentistry, orthopedics, ophthalmology, and otorhinolaryngology, especially in the direction of orthopedics and sports medicine research gradually increased, often applied to fracture non-healing, tendon and ligament injuries, osteoarthritis, muscle injuries, etc., especially in refractory tendinopathy and ligament degenerative lesions, with better clinical efficacy (46, 47).

Platelet-rich plasma injections are a common clinical treatment for chronic tendinopathies. According to statistics, approximately more than 86,000 athletes in Europe and the United States receive platelet-rich plasma treatment for tendon, ligament, or muscle injuries each year (48). The reason for this is that platelet-rich plasma is thought to contain concentrated amounts of a variety of growth factors, including platelet-derived growth factor, transforming growth factor beta and insulin-like growth factor, which have the ability to promote tendon healing (49, 50). Platelet-rich plasma is largely prepared from the patient's own plasma in clinical applications and has an excellent safety profile, with few adverse effects in published randomized controlled clinical trials (51). Many platelet-rich plasma kits are commercially available for use in orthopedic clinics. In addition, platelet-rich plasma is non-invasive in its injectable form and can be easily administered in the clinical setting (16). Researchers have mostly studied the efficacy of platelet-rich plasma in tendinopathies using a randomized controlled clinical trial approach, with a particular focus on the treatment of humeral epicondylitis (35) ZHANG et al. (52) used data from United States. health insurance agencies to count patients treated with platelet-rich plasma injections across the United States between 2010 and 2011 and found that the main tendinopathies treated with platelet-rich plasma injections included rotator cuff injuries, humeral epicondylitis, and plantar fasciitis.

Platelet-rich plasma is often used in combination therapy for tendon ligament injuries and is often combined with physiotherapy based on a centrifugal exercise in platelet-rich plasma injections for rotator cuff injuries (31), humeral epicondylitis (30), Achilles tendinopathy (22), and patellar tendinopathy (36), with good clinical outcomes. Platelet-rich plasma combined with stenting techniques to promote ACL injury repair has also been studied to a small extent (25). In recent years, platelet-rich plasma combined with mechanical stimulation for tendon ligament injuries has gradually gained attention. Currently, animal studies have shown that mechanical stimulation combined with platelet-rich plasma can effectively promote early healing of the bony-tendon interface after rotator cuff injury (53).

Although platelet-rich plasma is widely used in the treatment of tendon ligament injuries, there are many conflicting results reported on the therapeutic effects of platelet-rich plasma.DRAGOO et al. (8) Injected platelet-rich plasma combined with centrifugal exercise accelerated the recovery of patellar tendinitis in patients with patellar tendinitis.BOESEN et al. (54) evaluated patients' pain scores (VISA-A) before and 6, 12, and 24 weeks after injection, and found that platelet-rich plasma combined with centrifugal training for chronic achilles tendinopathy was more effective in reducing pain, improving mobility, reducing tendon thickness and intra-tendon vascular density. In contrast, de Vos RJ et al. (24) used a randomized control method to randomize 54 patients (>2 months duration) with chronic mid-portion achilles tendinopathy into two groups after platelet-rich plasma or saline injection combined with 12 weeks of centrifugal exercise training. Patient pain scores (VISA-A) were assessed before and 6, 12, and 24 weeks after injection, and showed that platelet-rich plasma injection did not improve patient pain scores compared with placebo. For this contradictory result to occur, it may be closely related to some influencing factors.

The research hotspot regarding platelet-rich plasma in the treatment of tendinopathies since 2003 has transitioned from the study of the effect of platelet-rich plasma on disease treatment alone to the study of the biological mechanisms of platelet-rich plasma in tendinopathies. Platelet-rich plasma contains many different growth factors and cytokines. Numerous in vitro and animal model studies have shown that platelet-rich plasma positively affects tendon healing by releasing these bioactive proteins to promote collagen expression, angiogenesis and cell migration, differentiation, and proliferation and to increase extracellular matrix production. Platelet-rich plasma contains cytokines that activate multiple cellular transduction pathways, and some of these signaling molecules located downstream of individual receptors can inhibit or further enhance the activation of other pathways regulated by different receptors. For example, in mediating inflammation for pain relief, platelet-rich plasma contains interleukin 1β and interleukin 10, which are known to be inflammation-activating factors in intracellular signaling pathways, and the interleukin 10 signaling pathway can inhibit interleukin 1β-activated pathways and reduce the expression of pro-inflammatory genes (86). ZHANG (87) found that hepatocyte growth factor in platelet-rich plasma antagonized interleukin 1β and inhibited the expression of cyclooxygenase 1, cyclooxygenase 2, prostaglandin E2 synthase genes and prostaglandin E2 production in patellar tendon cells, thereby modulating the local inflammatory response and reducing pain. In addition, hepatocyte growth factor in platelet-rich plasma inhibits the inflammatory response of the diseased tendon by increasing the expression of IκBα (88). In terms of promoting stem cell migration, differentiation, and cellular proliferation, platelets secrete platelet-derived growth factor B, fibroblast growth factor β, chemokine CXCL (89), VEGF, endothelial growth factor, hepatocyte growth factor (40), and many other cytokines, which can provide the initial signal for stem cell migration, increase circulating system-derived cells in tendons, and promote cellular behaviors such as proliferation and differentiation. The activation of signaling pathways and cellular responses in platelet-rich plasma during the treatment of tendinopathies still needs to be studied in more depth.