A comparison of different physical stimulation combined with platelet-rich plasma for the treatment of knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Platelet-rich plasma (PRP) contains various growth factors and inflammatory regulators, which can effectively reduce inflammation in joints and promote tissue repair. Multiple studies have proved its effectiveness in the treatment of knee osteoarthritis (KOA). Low-intensity focused ultrasound (LIFU) and transcutaneous electrical nerve stimulation (TENS) are non-invasive and safe physical therapy methods for KOA. This study is the first to propose the treatment of KOA with physical stimulation after PRP treatment, and to observe the clinical efficacy of the treatment method. METHODS: This is a protocol paper that outlines a randomized controlled trial, patients will be assigned randomly to the PRP group, PRP+LIFU group, PRP+TENS group, and PRP+LIFU combined TENS group. The patients will be followed at 12-week and 24-week time points to evaluate the primary and secondary outcomes of the study. The primary outcome is the VAS pain score. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Knee Documentation Committee scores (IKDC). After baseline examination, all patients will sign a written informed consent for study participation after a full explanation of the treatment protocol. We have planned a total of 120 patients (30 patients per group). DISCUSSION: The objective of this clinical trial is to evaluate the effect of different physical stimulation after PRP treatment for KOA. The data will be published after the completion of the study. TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trials Registry. REGISTRATION NUMBER: ChiCTR2200065119 (registered date: 10/28/2022).

Exoskeleton-Assisted Walking for Pulmonary and Exercise Performances of SCI Individuals.

OBJECTIVE: To determine whether exoskeleton-assisted walking (EAW) improves pulmonary ventilation function, motor function and related body structure, and activities equivalently as the conventional exercise program for people with spinal cord injury (SCI). METHODS: Forty participants (7 females and 33 males; age 37.1±12.0 years) with thoracic SCI were randomized into two groups and undertook 16 sessions of 50-60 min training (4 days/week). Participants in the EAW group received EAW trainings, such as assisted standing, walking, and climbing the stairs. The control group received a conventional exercise program. Outcomes were measured at baseline and upon completion of treatment. RESULTS: After trainings, the EAW group improved more than the control group in the forced vital capacity (FVC, 0.53 L [0.01-1.06 L]), predicted FVC% (19.59 [6.63-32.54]) and forced expiratory volume in 1s (0.61 L [0.15-1.07 L]), basic activities of daily living (BADL) (19.75 [10.88-28.62]), and distal femoral cartilage. Participants in the EAW group completed 6-minute walk test with median 17.3 meters while wearing the exoskeleton. There was no difference in trunk and lower extremity motor function, bone mineral density, and adverse events ( P > 0.05). CONCLUSION: In people with lower thoracic neurological level of SCI, EAW training has potential benefits to facilitate pulmonary ventilation function, walking, BADL and thickness of cartilage comparing to a conventional excise program. SIGNIFICANCE: This study provided more evidence for using EAW in clinic, and partly proved EAW had equivalent effects as conventional exercise program, which may combine with conventional exercise program for reducing burden of therapists in the future.

Pulsed electromagnetic fields for the management of knee osteoarthritis: multicentre, randomised, controlled, non-inferiority trial protocol.

INTRODUCTION: Pulsed electromagnetic field (PEMF) is an available treatment for knee osteoarthritis (KOA), which is the most common cause of pain and disability. Nonetheless, whether the clinical effects are like that of most used drugs is unclear. Thus, this study aims to determine the effect of PEMF on pain relief by comparing them with the positive drug (celecoxib). Furthermore, this clinical trial aims to evaluate the effect of PEMF on function and quality of life with a long-term follow-up. METHODS AND ANALYSIS: This two-armed, non-inferiority, randomised, controlled trial will be conducted in the outpatient physiatry/physiotherapy clinic or inpatient ward of 17 hospitals in China. A total of 428 individuals will be included who are more than 40 years of age with diagnosed KOA. The participants will be randomly allocated to the PEMF group: receiving a 6-week PEMF (15 Hz, 30 mT) at a frequency of 40 min per day, 5 days per week plus sham drug (n=214), or drug group: receiving a 6-week celecoxib 200 mg combined with sham PEMF (n=214). Clinical outcomes will be measured at baseline (T0), mid-term of intervention (T1), post-intervention (T2), 10, 18 and 30 weeks (T3-5) of follow-up after randomisation. The primary outcome will be the Western Ontario and McMaster Universities (WOMAC) pain index. The secondary outcomes will be WOMAC function and stiffness, pain measured by numerical rating score, quality of life, 6-minute walk test, pain catastrophising scale and responder index. ETHICS AND DISSEMINATION: The trial is performed following the Declaration of Helsinki. The study protocol and consent form have been approved by the Ethics Committee on Biomedical Research of West China Hospital of Sichuan University (#2021-220). All patients will give informed consent before participation and the trial is initiated after approval. Results of this trial will be disseminated through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100052131.

The Effect of Different Frequencies of Pulsed Electromagnetic Fields on Cartilage Repair of Adipose Mesenchymal Stem Cell-Derived Exosomes in Osteoarthritis.

BACKGROUND: The intra-articular injection of mesenchymal stem cell (MSC)-derived exosomes has already been proved to reverse osteoarthritic cartilage degeneration. Pulsed electromagnetic field (PEMF) has been found to regulate the biogenic function of MSCs. However, the effect of PEMF on MSC-derived exosomes has not yet been characterized. The aim of this study was to elucidate the regulatory role of different frequencies of PEMF in promoting the osteoarthritic cartilage regeneration of MSC-derived exosomes. METHODS: The adipose tissue-derived MSCs (AMSCs) were extracted from the epididymal fat of healthy rats and further exposed to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. The chondrocytes were treated with interlukin-1ß (IL-1ß) and the regenerative effect of co-culturing with PEMF-exposed AMSC-derived exosomes was assessed via Western blot, quantitative polymerase chain reaction, and ELISA assays. A rat model of osteoarthritis was established by anterior cruciate ligament transection (ACLT) surgery and received 4 times intra-articular injection of PEMF-exposed AMSC-derived exosomes once a week. After 8 weeks, the knee joint specimens of rats were collected for micro-computed tomography and histologic analyses. RESULTS: PEMF-exposed AMSC-derived exosomes could be endocytosed with IL-1ß-induced chondrocytes. Compared with the AMSC-derived exosomes alone, the PEMF-exposed AMSC-derived exosomes substantially suppressed the inflammation and extracellular matrix degeneration of IL-1ß-induced chondrocytes as shown by higher expression of transcripts and proteins of COL2A1, SOX9, and ACAN and lower expression of MMP13 and caspase-1. Of these, the 75-Hz PEMF presented a more significant inhibitive effect than the 15-Hz and 45-Hz PEMFs. Furthermore, the intra-articular injection of 75-Hz PEMF-exposed exosomes could obviously increase the number of tibial epiphyseal trabeculae, lead to a remarkable decrease in Osteoarthritis Research Society International score, and upregulate the COL2A1 and ACAN protein level of the degenerated cartilage. CONCLUSION: The present study demonstrated that PEMF stimulation could effectively promote the regeneration effects of AMSC-derived exosomes on osteoarthritic cartilage. Compared with other frequency parameters, the PEMF at a frequency of 75 Hz showed a superior positive effect on AMSC-derived exosomes in suppressing the IL-1ß-induced chondrocyte inflammation and extracellular matrix catabolism, as well as the osteoarthritic cartilage degeneration.

Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis.

Osteoarthritis, as a degenerative disease, is a common problem and results in high socioeconomic costs and rates of disability. The most commonly affected joint is the knee and characterized by progressive destruction of articular cartilage, loss of extracellular matrix, and progressive inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored as a new regenerative treatment for knee osteoarthritis in recent years. However, the detailed functions of MSC-based therapy and related mechanism, especially of cartilage regeneration, have not been explained. Hence, this review summarized how to choose, authenticate, and culture different origins of MSCs and derived exosomes. Moreover, clinical application and the latest mechanistical findings of MSC-based therapy in cartilage regeneration were also demonstrated.

Exoskeleton-assisted walking improves pulmonary function and walking parameters among individuals with spinal cord injury: a randomized controlled pilot study.

BACKGROUND: Exoskeleton-assisted walking (EAW) is expected to improve the gait of spinal cord injury (SCI) individuals. However, few studies reported the changes of pulmonary function (PF) parameters after EAW trainings. Hence, we aimed to explore the effect of EAW on PF parameters, 6-min walk test (6MWT) and lower extremity motor score (LEMS) in individuals with SCI and to compare those with conventional trainings. METHODS: In this prospective, single-center, single-blinded randomized controlled pilot study, 18 SCI participants were randomized into the EAW group (n = 9) and conventional group (n = 9) and received 16 sessions of 50-60 min training (4 days/week, 4 weeks). Pulmonary function parameters consisting of the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow (FEF), peak expiratory flow, and maximal voluntary ventilation, 6MWT with assisted devices and LEMS were reported pre- and post-training. RESULTS: Values of FVC (p = 0.041), predicted FVC% (p = 0.012) and FEV1 (p = 0.013) were significantly greater in EAW group (FVC: 3.8 ± 1.1 L; FVC% pred = 94.1 ± 24.5%; FEV1: 3.5 ± 1.0 L) compared with conventional group (FVC: 2.8 ± 0.8 L; FVC% pred = 65.4 ± 17.6%; FEV1: 2.4 ± 0.6 L) after training. Participants in EAW group completed 6MWT with median 17.3 m while wearing the exoskeleton. There was no difference in LEMS and no adverse event. CONCLUSIONS: The current results suggest that EAW has potential benefits to facilitate PF parameters among individuals with lower thoracic neurological level of SCI compared with conventional trainings. Additionally, robotic exoskeleton helped walking. TRIAL REGISTRATION: Registered on 22 May 2020 at Chinese Clinical Trial Registry (ChiCTR2000033166). http://www.chictr.org.cn/edit.aspx?pid=53920&htm=4 .

Conservative treatment of partial-thickness rotator cuff tears and tendinopathy with platelet-rich plasma: A systematic review and meta-analysis.

OBJECTIVE: To assess the effect of platelet-rich plasma as a conservative therapy in individuals with partial-thickness rotator cuff tears or tendinopathy on pain, and function. DATA SOURCES: Embase, MEDLINE, CENTRAL, Web of Science, CINAHL, PEDro, and the grey literature (to 31 March 2021). METHODS: Randomized controlled trials in English that reported short-term (6 ± 1 months), or long-term (⩾1 year) outcomes (shoulder pain or function) were conducted. Two independent reviewers screened the literature, completed the assessment of the Cochrane's risk of bias and extracted the data. Mean difference or standardized mean difference was used for continuous data. Heterogeneity was identified with I2 test. RESULTS: A total of 11 studies were eligible, and nine studies (n = 629) were included in this meta-analysis, that showed statistically significant short-term effects of platelet-rich plasma on pain relief (MD = -1.56; 95% CI -2.82 to -0.30), Constant-Murley score (MD = 16.48; 95% CI 12.57 to 20.40), and Shoulder Pain and Disability Index (MD = -18.78; 95% CI -36.55 to -1.02). Nonetheless, no long-term effect was observed on pain and function, except Constant-Murley score (MD = 24.30; 95% CI 23.27 to 25.33). The results of minimal important difference reached the minimal clinically important difference, except American Shoulder and Elbow Surgeons. For subgroup analysis, differences of pain relief were statistically significant in platelet-rich plasma-treated groups with double centrifugation, single injection, and post-injection rehabilitation. CONCLUSION: Our results suggested platelet-rich plasma had positive effects on pain relief and functional improvement for partial-thickness rotator cuff tears and rotator cuff tendinopathy, although the effects may not last for a long time.

The safety and feasibility of a new rehabilitation robotic exoskeleton for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI): an observational study.

STUDY DESIGN: A pre-post observational study. OBJECTIVES: To evaluate the safety and feasibility of a new rehabilitation robotic device for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI). SETTING: Three hospitals in Sichuan Province, China. METHODS: Individuals aged 15-75 years with an SCI between vertebrae six (T6) and lumbar 1 (L1) and complete motor paralysis participated in an exoskeletal-assisted walking (EAW) programme (2 weeks, 5 days/week, 30 min/day). Data were collected pre-, mid- (week 1) and post-intervention (week 2). RESULTS: Twenty-eight individuals (mean age = 41.3, 71% males) participated in the EAW programme. The distance walked during the 6-min walking test (6MWT) increased relative to that at baseline, during week 1 (13.0 ± 5.3 m) and week 2 (16.2 ± 5.3 m) when wearing the exoskeleton. The walking speed during the 10-m walking test (10MWT) increased from 0.039 ± 0.016 to 0.045 ± 0.016 m/s. The Hoffer walking ability grade, the Spinal Cord Independence Measure (SCIM), and the Walking Index for SCI II (WISCI II) changed after 2 weeks of EAW. No improvement in lower extremity motor score (LEMS) was observed. The rates of adverse events and serious adverse events were 21% and 4%, respectively. CONCLUSIONS: The EAW programme with the new robotic exoskeleton provided potential meaningful improvements in mobility for individuals with SCI and had few adverse events.