Definition of Synovial Mesenchymal Stem Cells for Meniscus Regeneration by the Mechanism of Action and General Amp1200 Gene Expression.

The quality control (QC) of pharmaceutical-grade cell-therapy products, such as mesenchymal stem cells (MSCs), is challenging. Attempts to develop such products have been hampered by difficulties defining cell-type-specific characteristics and therapeutic mechanisms of action (MoAs). Although we have developed a cell therapy product, FF-31501, consisting of human synovial MSCs (SyMSCs), it was difficult to find specific markers for SyMSCs and to define the cells separately from other MSCs. The purpose of this study was to create a method for identifying and defining SyMSCs from other tissue-derived MSCs and to delve deeper into the mechanism of action of SyMSC-induced meniscus regeneration. Specifically, as a cell-type-dependent approach, we constructed a set of 1143 genes (Amp1200) reported to be associated with MSCs and established a method to evaluate them by correlating gene expression patterns. As a result, it was possible to define SyMSCs separately from other tissue-derived MSCs and non-MSCs. In addition, the gene expression analysis also highlighted TNSF-15. The in vivo rat model of meniscus injury found TNSF-15 to be an essential molecule for meniscus regeneration via SyMSC administration. This molecule and previously reported MoA molecules allowed an MoA-dependent approach to define the mechanism of action for SyMSCs. Therefore, SyMSCs for meniscus regeneration were defined by means of two approaches: the method to separate them from other MSCs and the identification of the MoA molecules. These approaches would be useful for the QC of cell therapy products.

The applied study to improve the treatment of knee sports injuries in ultimate frisbee players based on personalized exercise prescription: a randomized controlled trial.

Objective: Ultimate frisbee can lead to severe sports injuries, especially joint injuries in the lower limbs, such as knee meniscus injuries. This study examines the impact of personalized exercise therapy on knee meniscus injuries in ultimate frisbee players in the Lingnan region of China. Methods: Seventy-six patients with confirmed meniscal injuries participated in the study, divided into an intervention group (n = 38) and a control group (n = 38). The control group received standard treatment, including drug therapy and physical therapy. The intervention group received standard treatment plus a personalized exercise regimen based on FITT-VP (frequency, intensity, time, type, volume, and progression) principles, incorporating strength training, aerobic exercise, flexibility training, neuromuscular training, and aquatic exercise. This program was monitored and adjusted over a six-month period through both online and offline methods. The primary outcomes were joint range of motion (ROM), thigh circumference atrophy index (TCAI), Lysholm Rating Scale (LRS) scores, and visual analog scores (VAS). The secondary outcome was the International Knee Documentation Committee (IKDC) score. Data were collected before the intervention, and at 1 month and 6 months after the intervention. Statistical analysis was conducted using SPSS 24.0 and GraphPad 10.0, with a significance level set at α = 0.05. Results: After 1 month, the intervention group showed significantly better results in ROM (116.67 ± 9.063), LRS score (86.316 ± 3.750), and IKDC score (80.473 ± 5.421) compared to the control group (111.784 ± 4.778, 82.579 ± 3.818, and 77.684 ± 4.430, respectively) (p < 0.05). The TCAI (3.219 ± 1.889) and VAS score (1.921 ± 0.673) in the intervention group were significantly lower than those in the control group (5.228 ± 2.131 and 2.710 ± 1.112, respectively) (p < 0.01). After 6 months, the differences in LRS and VAS scores between the groups were not significant. However, the intervention group continued to show significant improvements in ROM (134.934 ± 3.011), TCAI (1.107 ± 1.158), and IKDC score (93.315 ± 1.847) compared to the control group (125.395 ± 18.554, 4.574 ± 1.109, and 87.789 ± 4.437, respectively) (p < 0.05). Conclusion: Personalized exercise prescriptions offer significant therapeutic and rehabilitative benefits for ultimate frisbee players with knee meniscus injuries. This approach helps to reduce symptoms, alleviate pain, and improve joint function, muscle strength, and athletic performance after sports-related injuries.

Meniscus Injuries in Soccer.

Soccer is considered the most popular sport in the world. The game involves frequent agile maneuvers, such as rapid accelerations/decelerations and pivoting, and carries an inherent risk of high-speed collisions, which can lead to lower extremity injury. Knee and meniscus injuries can cause significant pain and disability, precluding participation in the sport. Understanding the diagnosis and management of meniscal injuries in soccer players is essential to the care of these athletes. This paper reviews meniscal anatomy, biomechanics, and mechanisms of injury; discusses the work-up, diagnosis, and management of meniscus injuries; and reports on rehabilitation, return to sport, and outcomes after meniscal injuries in soccer players.

Evaluation of orthobiological ozonized platelet-rich plasma therapy post-arthroscopic suturing and lone partial meniscectomy in the treatment of meniscal tears within degenerative knee osteoarthritis.

BACKGROUND: Knee joint osteoarthritis (OA)-related meniscal tears are still sometimes treated in centers by arthroscopic partial meniscectomy (APM), which is then followed by a solitary physical therapy regimen. OBJECTIVE: The present study was conducted to compare the efficacy of intra-articular injection of ozonized platelet-rich plasma (PRP) and hyaluronic acid following arthroscopic suturing, and APM to treat meniscal tear degenerative type. METHODS: In a randomized trial of prospective comparative research, 104 patients, all of whom had meniscal tears due to OA of the knee, were randomly divided into two groups. The participants in Group A (55 patients) were given intra-articular ozonized PRP and hyaluronate therapeutics, following arthroscopic suturing of meniscal tear treatment (ASMT) of degenerative knee joint OA. Group B (49 patients) was prepared for APM alone. Both groups were followed by physical therapy and a follow up visit throughout 12, 24, and 36 months. The WOMAC and Lequesne scores were evaluated. RESULTS: At every follow up visit for 6, 12, and 24, months, there was a significant decline in the mean of WOMAC and Lequesne scores in Groups A and B relative to baseline. Additionally, Group A significantly (P<0.0001) outperformed Group B at 12, 24, and 36 months for both Lequesne's and WOMAC scores. There were infection, stiffness, and widespread OA knee degeneration detected in Group B while no serious adverse effects were observed in Group A. CONCLUSION: The study's findings demonstrated that physical and intra-articular orthobiological ozonized PRP and hyaluronate therapies were more effective than APM in treating degenerative knee joint OA.

Skeletal Stem Cell-Derived Exosomes Promote Meniscal Tear Healing and Ameliorate Secondary Osteoarthritis.

BACKGROUND: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region. HYPOTHESIS: Local delivery of skeletal stem cell (SSC)-derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression. STUDY DESIGN: Controlled laboratory study. METHODS: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (GCON) and group treated with exosomes (GExosome). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms. RESULTS: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro (P < .01). The GExosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the GCON at 8 weeks postoperatively (P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the GCON, meniscal tissue in the GExosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the GCON than in the GExosome (P < .05). Compared with the GCON, the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family. CONCLUSION: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components. CLINICAL RELEVANCE: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region.

Emerging biologic augmentation strategies for meniscal repair: a systematic review.

BACKGROUND: Meniscal repair should be the gold standard. However, the meniscus is poorly vascularized and even an excellent meniscus repair may not heal. Therefore, numerous studies and systematic reviews have been carried out on platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and fibrin clots for meniscal augmentation, but the results remain controversial. This systematic review aimed to identify other emerging strategies for meniscal repair augmentation and to assess whether there are different avenues to explore in this field. METHODS: A systematic literature review was conducted in August 2022. PubMed, Ovid MEDLINE(R) all, Ovid All EBM Reviews, Ovid Embase and ISI Web of Science databases were searched. In Vivo animal and human studies concerning the biological augmentation of meniscal lesions by factors other than PRP, MSCs or fibrin clots were included. Cartilage-only studies, previous systematic reviews and expert opinions were excluded. All data were analyzed by two independent reviewers. RESULTS: Of 8965 studies only nineteen studies covering 12 different factors met the inclusion criteria. Eight studies investigated the use of growth factors for meniscal biologic augmentation, such as vascular endothelial growth factor or bone morphogenic protein 7. Five studies reported on cell therapy and six studies focused on other factors such as hyaluronic acid, simvastatin or atelocollagen. Most studies (n = 18) were performed on animal models with gross observation and histological evaluation as outcomes. Polymerase chain reaction and immunohistochemistry were also common. Biomechanical testing was the object of only two studies. CONCLUSIONS: Although several augmentation strategies have been attempted, none has yielded conclusive results, testifying to a lack of understanding with regard to meniscal healing. More research is needed to better understand the pathways that regulate meniscus repair and how to act positively on them. LEVEL OF EVIDENCE: Systematic review of case-control and animal laboratory studies.

Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol.

INTRODUCTION: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. METHODS AND ANALYSIS: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ISRCTN87336549.

Long-term effects of exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear: A meta-analysis of randomized controlled trials.

BACKGROUND: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression. RESULTS: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods. CONCLUSION: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM.

Hypermobile lateral meniscus: A systematic review of current treatment options.

PURPOSE: The reliable data on the incidence of hypermobile lateral meniscus (HLM) and its clinical manifestations, diagnostic methods and therapeutic approaches are limited. This systematic study aimed to review available treatment options for HLM and the outcomes of each approach. METHODS: A systematic search was performed in four electronic databases (PubMed, EMBASE, Scopus, Web of Science) to identify studies in which arthroscopically confirmed cases of HLM were treated surgically or nonsurgically, and the required data comprising study characteristics, patient data, treatment approaches and outcome measures were extracted from eligible studies. RESULTS: Twenty studies with a total of 212 patients (138 males and 74 females) and 219 knees were included. The most frequently reported symptoms were locking sensations, knee pain, giving way and snapping. Treatments used by the studies were: radiofrequency energy in two studies; arthroscopic partial meniscectomy in one study; open surgery in two studies; and arthroscopic meniscal repair in 17 studies. Eleven studies used an all-inside repair method and an inside-out meniscal repair was reported in eight studies. Three studies reported the usage of posterior arthroscopy for therapeutic or diagnostic approaches. Evaluation of symptom resolution was the main outcome measurement for which almost all of the studies stated relief of symptoms after intervention. CONCLUSION: Despite the lack of definite consensus about the most appropriate intervention for HLM, therapeutic preference was directed towards arthroscopic all-inside and inside-out repair techniques. Although the surgeon's decision remains the key factor in choosing the most suitable treatment option for each individual, posterior arthroscopic meniscal repair may be considered as a better option for HLM treatment according to the findings of this review. LEVEL OF EVIDENCE: Level IV.

Early Surgery Versus Exercise Therapy and Patient Education for Traumatic and Nontraumatic Meniscal Tears in Young Adults-An Exploratory Analysis From the DREAM Trial.

OBJECTIVE: To compare the effect of early meniscal surgery versus exercise and education with the option of later surgery on pain, function, and quality of life in young patients with a meniscal tear, taking symptom onset into account. DESIGN: Randomized controlled trial. METHODS: In a randomized controlled trial (the "Danish RCT on Exercise versus Arthroscopic Meniscal surgery for young adults" [DREAM] trial), 121 patients aged 18-40 years with a magnetic resonance imaging-verified meniscal tear were randomized to surgery or 12 weeks of supervised exercise and patient education. For this exploratory study, the analyses were stratified by symptom onset (traumatic/nontraumatic). The main outcome was the difference in change after 12 months in the mean score of 4 Knee injury and Osteoarthritis Outcome Score subscales (KOOS4) covering pain, symptoms, function in sport and recreation, and quality of life. RESULTS: Forty-two patients (69%) in the exercise therapy group and 47 (78%) in the surgery group were categorized as having a traumatic tear. We observed no difference in change in the KOOS4 after 12 months between the 2 treatment groups for either traumatic tears (18.8 versus 16.0 in the surgery versus exercise therapy groups; adjusted mean difference, 4.8 [95% confidence interval, -1.7 to 11.2]) or nontraumatic tears (20.6 versus 17.3 in the surgery versus exercise therapy groups; adjusted mean difference, 7.0 [95% confidence interval, -3.7 to 17.7]). CONCLUSION: In patients with traumatic and nontraumatic meniscus tears, early meniscal surgery did not appear superior to exercise and education in improving pain, function, and quality of life after 12 months. Further research is needed to confirm the clinical applicability of these findings. J Orthop Sports Phys Ther 2024;54(5):1-10. Epub 22 February 2024. doi:10.2519/jospt.2024.12245.

Physical Therapist Interventions Versus or Combined With Surgical Treatment in Nontraumatic Degenerative Meniscal Pathology: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: This study aimed to synthesize the evidence from randomized clinical trials in people with nontraumatic degenerative meniscal pathology by comparing physical therapist interventions versus or combined with arthroscopic partial meniscectomy (APM). METHODS: Seven electronic databases were searched. Methodological quality was evaluated using the Physiotherapy Evidence Database scale. Data synthesis was performed with random-effects network meta-analysis, and results were summarized using the standardized mean differences. RESULTS: From 2103 studies, 10 randomized clinical trials comprising 1411 individuals were included. Ninety percent of the selected randomized clinical trials were classified as good quality according to the Physiotherapy Evidence Database scale. All interventions (physical therapist interventions, APM, and APM plus physical therapist interventions) showed reduced pain and physical impairments at 3-month follow-up. However, when a physical therapist intervention was included, greater reductions in pain at rest (APM vs physical therapist interventions: 0.73 [95% CI = 0.20 to 1.26]; APM vs APM plus physical therapist interventions: 0.59 [95% CI = 0.15 to 1.03]) and greater increases in the strength of knee extensor muscles (APM vs physical therapist interventions: 0.44 [95% CI = 0.07 to 0.80]; APM vs APM plus physical therapist interventions: 0.73 [95% CI = 0.29 to 1.16]) were observed at 3 months. By contrast, no differences were found between treatments beyond 3 months. CONCLUSION: Physical therapist interventions based on exercise programs demonstrate superior short-term outcomes in pain reduction and knee extensor strength compared to surgical treatment. IMPACT: For nontraumatic degenerative meniscal pathology, conservative treatment utilizing a physical therapist intervention approach should be prioritized as the first choice over surgical treatment. It offers comparable or superior short-term pain reduction and strength improvements, with a lower risk of side effects. In cases where surgery is deemed necessary, including postsurgical, physical therapist interventions are highly recommended to enhance muscle strength and alleviate pain.

Evaluation and Treatment of Knee Pain: A Review.

Importance: Approximately 5% of all primary care visits in adults are related to knee pain. Osteoarthritis (OA), patellofemoral pain, and meniscal tears are among the most common causes of knee pain. Observations: Knee OA, affecting an estimated 654 million people worldwide, is the most likely diagnosis of knee pain in patients aged 45 years or older who present with activity-related knee joint pain with no or less than 30 minutes of morning stiffness (95% sensitivity; 69% specificity). Patellofemoral pain typically affects people younger than 40 years who are physically active and has a lifetime prevalence of approximately 25%. The presence of anterior knee pain during a squat is approximately 91% sensitive and 50% specific for patellofemoral pain. Meniscal tears affect an estimated 12% of the adult population and can occur following acute trauma (eg, twisting injury) in people younger than 40 years. Alternatively, a meniscal tear may be a degenerative condition present in patients with knee OA who are aged 40 years or older. The McMurray test, consisting of concurrent knee rotation (internal or external to test lateral or medial meniscus, respectively) and extension (61% sensitivity; 84% specificity), and joint line tenderness (83% sensitivity; 83% specificity) assist diagnosis of meniscal tears. Radiographic imaging of all patients with possible knee OA is not recommended. First-line management of OA comprises exercise therapy, weight loss (if overweight), education, and self-management programs to empower patients to better manage their condition. Surgical referral for knee joint replacement can be considered for patients with end-stage OA (ie, no or minimal joint space with inability to cope with pain) after using all appropriate conservative options. For patellofemoral pain, hip and knee strengthening exercises in combination with foot orthoses or patellar taping are recommended, with no indication for surgery. Conservative management (exercise therapy for 4-6 weeks) is also appropriate for most meniscal tears. For severe traumatic (eg, bucket-handle) tears, consisting of displaced meniscal tissue, surgery is likely required. For degenerative meniscal tears, exercise therapy is first-line treatment; surgery is not indicated even in the presence of mechanical symptoms (eg, locking, catching). Conclusions and Relevance: Knee OA, patellofemoral pain, and meniscal tears are common causes of knee pain, can be diagnosed clinically, and can be associated with significant disability. First-line treatment for each condition consists of conservative management, with a focus on exercise, education, and self-management.

Treatment strategies for meniscal lesions: from past to prospective therapeutics.

Menisci play an important role in the biomechanics of knee joint function, including loading transmission, joint lubrication, prevention of soft tissue impingement during motion and joint stability. Meniscal repair presents a challenge due to a lack of vascularization that limits the healing capacity of meniscal tissue. In this review, the authors aimed to untangle the available treatment options for repairing meniscal tears. Various surgical procedures have been developed to treat meniscal tears; however, clinical outcomes are limited. Consequently, numerous researchers have focused on different treatments such as the application of exogenous and/or autologous growth factors, scaffolds including tissue-derived matrix, cell-based therapy and miRNA-210. The authors present current and prospective treatment strategies for meniscal lesions.

One of the most common knee injuries, especially in athletes, is a meniscal tear. There are two wedge-shaped pieces of fibrocartilage that act as shock absorbers between the thighbone and shinbone (menisci). The menisci help to transmit weight from one bone to another and play an important role in knee stability. The challenge for researchers and clinicians is to repair meniscal injuries, despite the lack of vascularization. The authors discuss the available approaches for repairing meniscal tears. Non surgical and surgical procedures are reviewed, clarifying their clinical outcomes. Other approaches to tissue engineering are also discussed. Using the patient's cells may be a potential strategy to repair meniscal injuries and improve the durability of the knee joint.

Meniscus Root Tears: A Clinical Review.

ABSTRACT: Meniscus root tears are important to recognize early given their potentially devastating consequences on joint health. This injury results in the lost ability of the meniscus to transfer axial loads into hoop stress; therefore, it is functionally equivalent to a complete meniscectomy. This causes rapid progression of osteoarthritis and increased need to total knee arthroplasty in a previously healthy joint. Despite these consequences, root tears have only been discussed in the orthopedic literature in the last 10 to 15 years and have not been routinely integrated into nonoperative sports medicine education. It is important for all nonoperative sports medicine providers to properly diagnose and triage this injury early in its course to maximize joint preservation efforts. The goal of this manuscript is to review the anatomy, presentation, natural history, imaging, and treatment options for meniscal root tears.

Comparative clinical outcomes of different therapies for traumatic meniscal tears in adults: A protocol for systematic review and network meta-analysis.

BACKGROUND: Meniscus tears are usually classified as degenerative or traumatic tears according to their pathogenesis. At present, traumatic meniscal tears are generally believed to have high healing potential. In recent years, multiple treatments have been described for traumatic meniscal tears, such as the inside-out technique, outside-in technique, all-inside technique, biological augmentation of meniscal repair, meniscectomy, and non-surgical treatment. However, the functional recovery of the knee joint and healing of the meniscus after treatment are quite different from the results reported in the literature, which requires more reliable evidence-based medical findings. This study will evaluate evidence from multiple types of research comparing different therapies for traumatic meniscal tears in adults. METHODS: We will search the EMBASE, Cochrane Library (the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials [CENTRAL], Cochrane Methodology Register), PubMed, Web of Science (Science and Social Science Citation Index), China Knowledge Network, CBM, Wanfang data, and VIP electronic databases from their inception to August 10, 2021, with no language restrictions. We will also manually search Baidu and Google Scholar to identify randomized controlled studies, non-randomized controlled studies, and cohort studies on the treatment of traumatic meniscal tears. Two researchers will independently screen the literature, extract the data, and evaluate the quality of the studies. Software programs, including Microsoft Access, Excel, Stata (Version 15), WinBUGS (Version 1.4.3), and ADDIS (Version 1.16.8), were used to analyze and manipulate the data. RESULTS: In this study, the main outcomes were physical function and healing rate, based on the Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm Knee Scoring Scale, Knee Injury and Osteoarthritis Outcome Score, Functional Recovery Scale, and clinical healing rate. The secondary indexes included total cost, cost-effectiveness ratio, incremental cost-effectiveness ratio, Tegner activity scale score, visual analogue scale, numerical rating scale, and meniscal tear complications. CONCLUSIONS: This systematic review will provide reliable evidence-based findings for the clinical application of different therapies for traumatic meniscal tears in adults.

Early Surgery or Exercise and Education for Meniscal Tears in Young Adults.

BACKGROUND: Surgery is commonly used to treat meniscal tears; however, to our knowledge, no randomized controlled trials (RCTs) have compared surgery with nonsurgical alternatives in young adults. We hypothesized that early meniscal surgery would be superior to a strategy of exercise and education with the option of surgery later if needed. METHODS: In this pragmatic parallel-group RCT, we enrolled young adults (18-40 years of age) with magnetic resonance imaging­verified meniscal tears eligible for surgery from seven Danish hospitals. Patients were randomly assigned (1:1) to surgery (partial meniscectomy or meniscal repair) or 12-week supervised exercise therapy and education with the option of surgery later if needed. The primary outcome was the difference in change from baseline to 12 months in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, ranging from 0 (worst) to 100 (best). RESULTS: We enrolled 121 young adults (mean age, 29.7 years; 28% were female). In total, 107 participants (88%) completed the 12-month follow-up; 16 participants (26%) from the exercise group crossed over to surgery, while 8 (13%) from the surgery group did not undergo surgery. Intention-to-treat analysis showed no statistically significant difference in change between groups from baseline to 12 months in KOOS4 scores (19.2 vs. 16.4 in the surgery vs. exercise groups; adjusted mean difference, 5.4 [95% confidence interval, −0.7 to 11.4]). No difference in serious adverse events was observed (four vs. seven in the surgery and exercise groups, respectively; P=0.40). Per-protocol and as-treated analyses yielded similar results. CONCLUSIONS: Our results suggest that among young, active adults with meniscal tears, a strategy of early meniscal surgery is not superior to a strategy of exercise and education with the option of later surgery. Both groups experienced clinically relevant improvements in pain, function, and quality of life at 12 months, and one of four from the exercise group eventually had surgery. (Funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand; ClinicalTrials.gov number, NCT02995551.)

Arthroscopic Partial Meniscectomy versus Physical Therapy for Degenerative Meniscal Tear: a Systematic Review.

BACKGROUND: Meniscal tears are commonly observed in patients with knee osteoarthritis (OA), however, clinical significance of such lesions detected by magnetic resonance imaging is in many cases unclear. This study aimed to determine the clinical effectiveness of arthroscopic partial meniscectomy (APM) compared with non-operative care in patients with knee OA. METHOD: We used existing systematic reviews with updates of latest studies. Three randomized controlled studies were selected, where two studies compared the effects of APM plus physical therapy (PT) with PT alone and one compared APM alone and PT alone. While 1 study exclusively included OA patients, 2 studies included 21.1 and 12% of patients with no radiographic OA. Patients with knee locking were unanimously excluded. RESULTS: Upon comparison of APM plus PT and PT alone, there was no significant difference observed in knee function, physical activity, or adverse events. Knee pain was observed to be significantly lower in the APM plus PT group at 6 months, but there was no difference between the two groups at 12 and 24 months. With respect to the comparison between APM alone and PT alone, PT was non-inferior based on the criteria for knee function during 24 months; however, knee pain was significantly reduced in the APM alone group. CONCLUSIONS: Our study showed that knee pain was significantly improved in the APM group compared to non-operative care group at 6 months and over 24 months. Our result was based on only 3 randomized controlled trials (RCTs) revealing a significant knowledge gap, hence demanding more high-quality RCTs in OA patients. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020215965.

Effects of Platelet-Rich Plasma and Bone Marrow Mesenchymal Stem Cells on Meniscal Repair in the White-White Zone of the Meniscus.

OBJECTIVE: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. RESULTS: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group. CONCLUSION: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury.

In Vivo Studies of Mesenchymal Stem Cells in the Treatment of Meniscus Injury.

This review summarizes the literature of preclinical studies and clinical trials on the use of mesenchymal stem cells (MSCs) to treat meniscus injury and promote its repair and regeneration and provide guidance for future clinical research. Due to the special anatomical features of the meniscus, conservative or surgical treatment can hardly achieve complete physiological and histological repair. As a new method, stem cells promote meniscus regeneration in preclinical research and human preliminary research. We expect that, in the near future, in vivo injection of stem cells to promote meniscus repair can be used as a new treatment model in clinical treatment. The treatment of animal meniscus injury, and the clinical trial of human meniscus injury has begun preliminary exploration. As for the animal experiments, most models of meniscus injury are too simple, which can hardly simulate the complexity of actual meniscal tears, and since the follow-up often lasts for only 4-12 weeks, long-term results could not be observed. Lastly, animal models failed to simulate the actual stress environment faced by the meniscus, so it needs to be further studied if regenerated meniscus has similar anti-stress or anti-twist features. Despite these limitations, repair of the meniscus by MSCs has great potential in clinics. MSCs can differentiate into fibrous chondrocytes, which can possibly repair the meniscus and provide a new strategy for repairing meniscus injury.

Ultrasound-Guided Meniscal Injection of Autologous Growth Factors: A Brief Report.

Meniscal degeneration is a common finding even in young patients' knees, and it is regarded as a predictor for the onset of early osteoarthritis (OA). When symptomatic, it represents a challenge since arthroscopic surgery provides unpredictable results: recent evidence has shown that partial meniscectomy is not better than conservative management up to 2 years of follow-up, and the removal of meniscal tissue may accelerate OA progression toward OA. Intra-articular injection of corticosteroids or hyaluronic acid may help in providing temporary symptomatic relief, but no influence should be expected on the quality of the meniscal tissue. Biologic agents have been adopted to treat a variety of degenerative musculoskeletal pathologies, and the use of platelet-derived growth factors (GFs) has become routine. Preclinical studies have documented that platelet-derived GFs may play a beneficial role in stimulating meniscal repair and regeneration by triggering anabolic pathways and stimulating local mesenchymal stem cells from synovium. Furthermore, also mechanical stimulation (e.g., arthroscopic trephination or percutaneous needling) in the red-red or red-white zone may further promote tissue healing. The purpose of the present brief report is to describe the clinical outcomes at 18 months' follow-up in a cohort of patients affected by symptomatic medial meniscus degeneration and treated by percutaneous needling plus intra- and perimeniscal injection of autologous conditioned plasma (ACP). The procedure was shown to be safe and provided significant pain reduction and improvement in subjective scores. This treatment option deserves further investigation in a comparative setting, to establish whether it could offer advantage over isolated intra-articular injections.