This work was supported by Shanghai Critical Clinical Specialties Construction Project (Grant Number: Shslczdzk04001); the Sailing program of Shanghai Science and Technology Commission (Grant Number: 22YF1444300); Projects within the budget of Shanghai University of Traditional Chinese Medicine (Grant Number: 2021LK091).

Standardized Tuina Manipulation for Knee Osteoarthritis in Rats

<ol>
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The authors declare that they have no competing interests.

This study provides a protocol for Tuina manipulation on KOA rats. Through pain behavior tests and histomorphological findings, it suggested that such a series of Tuina manipulation applied to KOA rats could reduce synovial inflammation and cartilage apoptosis, which could be a reference of Tuina manipulation on animal models of KOA.
There are several critical procedures during the protocol. First, it&#39;s important to choose an appropriate method for inducing the KOA model. There are various...

Knee osteoarthritis (KOA) is a degenerative disease mainly manifested in joint pain. Fibrosis, cracking, ulceration, and loss of articular cartilage are the main causes of this disease1. KOA has a high prevalence and may result in a profound impact on the daily life of patients, causing disability in severe cases. Among people aged 45-84 years, the prevalence of KOA increases with age, and the prevalence among people aged 85 years and above is 15%, with a predominance in women2,3. In addition, KOA might bring a serious economic burden on both the individual and the society. A survey showed that direct health care costs on KOA per capita reached up to $8,858 &#177; $5,120 per year4. With the aging of society, KOA has become a worldwide health problem and a major social issue, as well as a topical issue for scientific research.
Evidence-based studies have shown the effectiveness of Tuina manipulation in treating KOA5. Tuina manipulation could relieve pain and improve dysfunction in KOA patients, the mechanism of which is related to anti-inflammatory effects6,7. Scholars found that Tuina manipulation effectively inhibited the expression of inflammatory factors interleukin (IL)-&#946; and 5-hydroxytryptamine and slowed down the degeneration of articular cartilage in a rabbit KOA model8. It suggested that Tuina could promote blood circulation and metabolism at the lesion site, which helped clear inflammatory factors such as IL-1, IL-6 and tumor necrosis factor (TNF)-&#945;, thereby alleviating the clinical symptoms of KOA9. In addition, the passive movement of the joint through Tuina manipulation can promote the penetration and diffusion of synovial fluid into the articular cartilage and improves tissue nutrient metabolism10. Other studies suggested that Tuina manipulation can effectively improve the biomechanical indexes in KOA patients11. Manipulations applied on soft tissues can improve stress distribution over limbs and enhance balance function12,13. At the same time, with some joint adjustment manipulations, the alignment of the lower limbs can also be adjusted to correct abnormal gaits14,15.
The mechanism of action of Tuina manipulation in treating KOA remains to be explored, and therefore, an experimental study is necessary. The key to the application of Tuina in experimental animals is the standardization of modeling, animal fixation and intervention methods16. The modeling method determines whether the experimental animal can exhibit the characteristics of the disease. Meanwhile, appropriate fixation methods can facilitate the intervention of the Tuina manipulation and better reflect the effect of Tuina. The standardization of intervention methods is the most difficult part of Tuina manipulation. In 2010, the basic system of Chinese acupuncture standards mentioned the acupuncture point standards for experimental animals, providing the possibility for acupuncture and Tuina operations in animal experiments17. However, there are still difficulties in standardizing Tuina manipulation. There are multiple types of Tuina manipulation18. The choice of the specific manipulation mainly depends on the disease to be treated and the therapeutic theories the performer prefers. In the study of Tuina for KOA, more attention has been paid to the point-pressing manipulation (pressing the specific acupoints with the thumb or elbow), Yizhichan pushing manipulation (a pushing manipulation by wiggling the thumb), and press and kneading manipulation (which refers to pressing and kneading the specific area of the body surface by finger or palm)19. Press and kneading manipulation is one of the most widely used Tuina manipulations, which combines pressing and kneading to move the subcutaneous tissue20. Press and kneading manipulation applied on acupoints can promote blood circulation and relieve pain and represents the therapeutic effect of Tuina on KOA19.
In this protocol, the operation of press and kneading manipulation on KOA rats will be described in detail, including selected acupoints, intensity and frequency of the manipulation and the body position of the rat, so as to provide a reference for future research.

<table><tbody><tr><td>absolute ethanol</td><td>Supelco</td><td>PHR1070</td><td>For making specimen</td></tr><tr><td>ALMEMO admeasuring apparatus</td><td>ahlborn</td><td>2450-1</td><td>For Mechanical Withdrawal Threshold test</td></tr><tr><td>Anti-Digoxin antibody</td><td>Sigma-Aldrich</td><td>SAB4200669</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Anti-IL-1 beta</td><td>abcam</td><td>ab283818</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>DAB Substrate kit</td><td>Solarbio</td><td>DA1010</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Denture base materials</td><td>Shanghai New Century</td><td>20000356</td><td>For model making</td></tr><tr><td>eosin</td><td>bioswamp&amp;nbsp;</td><td>PAB180016&amp;nbsp;</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Finger pressure recordings</td><td>Suzhou Changxian Optoelectronic Technology</td><td>CX1003w</td><td>For Tuina manipulation</td></tr><tr><td>formic acid solution</td><td>Sigma-Aldrich</td><td>695076</td><td>For decalcification</td></tr><tr><td>H2O2</td><td>Sigma-Aldrich</td><td>386790-M</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>hematoxylin</td><td>bioswamp&amp;nbsp;</td><td>PAB180015</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Isoflurane</td><td>Shanghai Yuyan Scientific Instrument Company</td><td>S10010533</td><td>For gas anesthesia</td></tr><tr><td>neutral resins</td><td>bioswamp&amp;nbsp;</td><td>PAB180017</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Paraformaldehyde Fix Solution</td><td>Sigma-Aldrich</td><td>100496</td><td>For histology</td></tr><tr><td>PBS</td><td>Sigma-Aldrich</td><td>P3813</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Plantar Test Apparatus</td><td>IITC Life Science</td><td>/</td><td>For Paw Withdrawal Latency test</td></tr><tr><td>plaster of Paris bandage</td><td>WANDE</td><td>20150023</td><td>For model making</td></tr><tr><td>Proteinase K</td><td>Sigma-Aldrich</td><td>124568</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>TNF Alpha Monoclonal antibody</td><td>Proteintech</td><td>60291-1-Ig</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>TUNEL&amp;nbsp;</td><td>Servicebio</td><td>GDP1042</td><td>For HE stain IHC or TUNEL</td></tr><tr><td>Wax</td><td>Sigma-Aldrich</td><td>327204</td><td>For making specimen</td></tr><tr><td>xylene</td><td>Shanghai Sinopharm Group</td><td>100092</td><td>For making specimen</td></tr></tbody></table>

tuina manipulation to reduce inflammation and cartilage loss in knee osteoarthritis rats

Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its mechanism. Therefore, the manipulation of animal models of knee osteoarthritis is critical. This protocol provides a standard process for Tuina manipulation on KOA rats and a preliminary exploration of the mechanism of Tuina for KOA. The press and kneading manipulation method (a kind of Tuina manipulation that refers to pressing and kneading the specific area of the body surface) is applied on 5 acupoints around the knee joint of rats. The force and frequency of the manipulation were standardized by finger pressure recordings, and the position of the rat during manipulation is described in detail in the protocol. The effect of manipulation can be measured by pain behavior tests and microscopic findings in synovial and cartilage. KOA rats showed significant improvement in pain behavior. The synovial tissue inflammatory infiltration was reduced in the Tuina group, and the expression of tumor necrosis factor (TNF)-&#945; was significantly lower. Compared to the control group, chondrocyte apoptosis was less in the Tuina group. This study provides a standardized protocol for Tuina manipulation on KOA rats and preliminary proof that the therapeutic effects of Tuina may be related to reducing synovial inflammation and delayed chondrocyte apoptosis.

Pain behavior tests 
The MWT results showed that the MWT of the right hind limb after modeling was significantly lower than before (p&#60;0.05). Compared with the control group, the MWT of rats was significantly elevated after Tuina (p&#60;0.05; Figure 5 and Table 2).
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/65451/65451fig05.jpg" /> 
Figure...

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Author Spotlight: Understanding the Mechanism of Tuina Manipulation in Rats 

We present a protocol for Tuina manipulation performed on plaster-immobilized-induced knee osteoarthritis rats. Based on the preliminary results, it suggested that the efficacy of the method relied on the reduction of inflammation and cartilage loss.

Tuina Manipulation to Reduce Inflammation and Cartilage Loss in Knee Osteoarthritis Rats

Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its ...

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Medicine

1.8K Views.  Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine. We present a protocol for Tuina manipulation performed on plaster-immobilized-induced knee osteoarthritis rats. Based on the preliminary results, it suggested that the efficacy of the method relied on the reduction of inflammation and cartilage loss.

Video: Author Spotlight: Understanding the Mechanism of Tuina Manipulation in Rats 

Preparation, Procedures and Evaluation of Platelet-Rich Plasma Injection in the Treatment of Knee Osteoarthritis

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department. Existing non-surgical treatments have a limited effect on the repair of cartilage and on bone regeneration. Platelet-rich plasma (PRP) is an autologous bioactive substance that can repair cartilage injury and accelerate bone regeneration effectively. However, reporting of PRP preparation protocols in clinical studies is highly inconsistent, with the majority of studies providing insufficient information to allow the protocol to be reproduced. We describe a repeatable method of preparing PRP visually, the treatment of KOA using PRP intra-articular injection, and methods of evaluating the outcome. PRP was prepared using manual double centrifugation. The PRP layer was extracted from peripheral blood and used for knee joint cavity injection. Evaluations included assessments of blood platelet concentrations and clinical outcomes. Preparation of PRP by manual centrifugation requires less apparatus and is less costly than plasma filtration or centrifugation using equipment. The centrifugation time of our double centrifugation method was 6 and 5 minutes for the respective centrifugations at forces of 800 and 1400 x g, respectively, to allow for the consistent preparation of standardized PRP. However, a manual method is susceptible to operator error, and PRP batch preparation is not available. Intra-articular injection of PRP proved to be an effective treatment for knee osteoarthritis. The entire treatment procedure took less than 30 minutes, the blood platelet concentration of PRP could be standardized, and treatment was proven to be effective when evaluated by follow-up.

Knee osteoarthritis is frequently seen in the orthopedic department. We introduce in detail the entire knee osteoarthritis treatment process with platelet-rich plasma injection, including preparation, procedures, and evaluation.

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department. Existing non-surgical treatments have a limited ...

Using a Knee Arthrometer to Evaluate Tissue-specific Contributions to Knee Flexion Contracture in the Rat

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ROM is called a joint contracture and results in increased morbidity. Due to the difficulty of reversing established knee contractures, early detection is important, and hence, knowing risk factors for their development is essential. The rat represents a good model with which the effect of an intervention can be studied due to the similarity of rat knee anatomy to that of humans, the rat's ability to tolerate long durations of knee immobilization in flexion, and because mechanical data can be correlated with histologic and biochemical analysis of knee tissue.
Using an automated arthrometer, we demonstrate a validated, precise, reproducible, user-independent method of measuring the extension ROM of the rat knee joint at specific torques. This arthrometer can be used to determine the effects of interventions on knee joint ROM in the rat.

The goal of the protocol is to measure the extension range of motion of the rat knee. The effects of various diseases that increase the stiffness of the knee joint and the effectiveness of treatments can be quantified.

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ...

The Lower Body Positive Pressure Treadmill for Knee Osteoarthritis Rehabilitation

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.

Here, based on a clinician&#8217;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in ...

Three-Dimensional Finger Motion Tracking during Needling: A Solution for the Kinematic Analysis of Acupuncture Manipulation

Three-dimensional (3D) motion tracking has been used in many fields, such as the researches of sport and medical skills. This experiment aimed to use 3D motion tracking technology to measure the kinematic parameters of the joints of fingers during acupuncture manipulation (AM) and establish three technical indicators "amplitude, velocity and time". This method can reflect the operation characteristics of AM and provide quantitative parameters along three axes of multiple finger joints. The current evidence shows that the method has great potential for future applications such as the study of the dose-effect relationship of acupuncture, teaching, and learning of AM, and the measurement and preservation of famous acupuncturists' AM.

This experimental method describes a solution for the kinematic analysis of acupuncture manipulation with three-dimensional finger motion tracking technology.

Three-dimensional (3D) motion tracking has been used in many fields, such as the researches of sport and medical skills. This experiment aimed to use 3D ...

Destabilization of the Medial Meniscus and Cartilage Scratch Murine Model of Accelerated Osteoarthritis

Osteoarthritis is the most prevalent musculoskeletal disease in people over 45, leading to an increasing economic and societal cost. Animal models are used to mimic many aspects of the disease. The present protocol describes the destabilization and cartilage scratch model (DCS) of post-traumatic osteoarthritis. Based on the widely used destabilization of the medial meniscus (DMM) model, DCS introduces three scratches on the cartilage surface. The current article highlights the steps to destabilize the knee by transecting the medial meniscotibial ligament followed by three intentional superficial scratches on the articular cartilage. The possible analysis methods by dynamic weight-bearing, microcomputed tomography, and histology are also demonstrated. While the DCS model is not recommended for studies that focus on the effect of osteoarthritis on the cartilage, it enables the study of osteoarthritis development in a shorter time window, with special focus on (1) osteophyte formation, (2) osteoarthritic and injury pain, and (3) the effect of cartilage damage in the whole joint.

The present protocol describes the controlled microblade scratches on the surface of the articular cartilage after destabilizing the mouse knee by cutting the medial miniscotibial ligament. This animal model presents an accelerated form of osteoarthritis (OA) suitable for studying osteophyte formation, osteosclerosis, and early-stage pain.

Osteoarthritis is the most prevalent musculoskeletal disease in people over 45, leading to an increasing economic and societal cost. Animal models are ...

FSN Therapy for Knee Osteoarthritis Pain Management

Fu's Subcutaneous Needling for Knee Osteoarthritis Pain

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting effects in soft tissue injuries, particularly in painful musculoskeletal conditions, by providing stimulation primarily in the subcutaneous area. Osteoarthritis (OA) is the most common joint disease in adults worldwide and is often accompanied by a painful syndrome of structural changes in the peripheral joints of the knee. However, the etiology of OA pain is not fully understood, though myofascial trigger points (MTrPs) are commonly found in the lower limb muscles (so-called "tightened muscles") of patients with knee OA. 
FSN has been used in many fields for the treatment of acute pain problems and can relieve muscle contraction from MTrPs, thereby improving the local circulation. This study recruited patients with pain from knee OA into an FSN group or a transcutaneous electrical nerve stimulation (TENS) group with three treatment sessions and a follow-up over the course of 2 weeks. The results showed that FSN was effective in treating soft tissue pain around the knee with OA. This study aimed to establish and visualize three key technical indicators during FSN therapy, including the FSN needle insertion point and layer; the frequency and duration of the swaying movement; and the manipulation of the reperfusion approach. These findings have great potential for future applications in myofascial pain treatment, especially for pain management. Following this protocol could enhance FSN skills.

Author Spotlight: Fu's Subcutaneous Needling for Knee Osteoarthritis Pain  

We present a protocol for using Fu's subcutaneous needling for knee osteoarthritis pain, which combines swaying movement and reperfusion approach techniques. This protocol has great potential for future applications in myofascial pain treatment and could enhance Fu's subcutaneous needling (FSN) manipulation skills.

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting ...

Tuina Therapy for Frozen Shoulders in a Rat Model

Tuina in a Frozen Shoulder Rat Model: An Efficient and Reproducible Protocol

Frozen shoulder (FS) is a common condition with no defined optimal therapy. Tuina therapy, a traditional Chinese medicine (TCM) technique used to treat FS patients in Chinese hospitals, has demonstrated excellent results, but its mechanisms are not fully understood. Building on a previous study, this work aimed to develop a Tuina protocol for an FS rat model. We randomly divided 20 SD rats into control (C; n = 5), FS model (M; n = 5), FS model Tuina treatment (MT; n = 5), and FS model oral treatment (MO; n = 5) groups. This study used the cast immobilization method to establish the FS rat model. The effect of Tuina and oral dexamethasone on the glenohumeral range of motion (ROM) was evaluated, and the histological findings were assessed. Our study showed that Tuina and oral dexamethasone were able to improve shoulder active ROM and preserve the structure of the capsule, with Tuina therapy proving to be more effective than oral dexamethasone. In conclusion, the Tuina protocol established in this study was highly effective for FS.

Author Spotlight: Investigating the Effectiveness of Tuina Therapy for Frozen Shoulder 

This study develops an efficient and reproducible Tuina protocol for treating frozen shoulder established in a rat model. This approach will help to study the Tuina therapy treatment method for frozen shoulders.

Frozen shoulder (FS) is a common condition with no defined optimal therapy. Tuina therapy, a traditional Chinese medicine (TCM) technique used to treat FS ...

Treating Knee Osteoarthritis with Tuina in a Rabbit Model

Tuina Intervention in Rabbit Model of Knee Osteoarthritis

Knee osteoarthritis (KOA) is mainly characterized by degenerative changes in the knee joint's cartilage and surrounding soft tissues. The efficacy of Tuina in treating KOA has been confirmed, but the underlying mechanism needs to be investigated. This study aims to establish a scientifically feasible KOA rabbit model treated with Tuina to reveal the underlying mechanisms. For this, 18, 6-month-old normal-grade male New Zealand rabbits were randomly divided into sham, model, and Tuina groups, with 6 rabbits in each group. The KOA model was established by injecting 4% papain solution into the knee joint cavity. The Tuina group was intervened with Tuina combined with the knee joint rotary correction method for 4 weeks. Only the standard grasping and fixation were performed in sham and model groups. At the end of the 1-week intervention, the knee joint range of motion (ROM) was observed, and cartilage hematoxylin-eosin (HE) staining was done. The study shows that Tuina could inhibit chondrocyte apoptosis, repair cartilage tissue, and restore knee joint ROM. In conclusion, this study demonstrates the scientific feasibility of Tuina treatment for KOA model rabbits, highlighting its potential application in the study of KOA and similar knee joint-related conditions.

Author Spotlight: Using a Rabbit Model to Explore the Efficacy of Tuina in Treating Knee Osteoarthritis 

The protocol describes a method for Tuina intervention in a rabbit model of knee osteoarthritis.

Knee osteoarthritis (KOA) is mainly characterized by degenerative changes in the knee joint's cartilage and surrounding soft tissues. The efficacy of ...

A Reproducible Cartilage Impact Model to Generate Post-Traumatic Osteoarthritis in the Rabbit

Post-traumatic osteoarthritis (PTOA) is responsible for 12% of all osteoarthritis cases in the United States. PTOA can be initiated by a single traumatic event, such as a high-impact load acting on articular cartilage, or by joint instability, as occurs with anterior cruciate ligament rupture. There are no effective therapeutics to prevent PTOA currently. Developing a reliable animal model of PTOA is necessary to better understand the mechanisms by which cartilage damage proceeds and to investigate novel treatment strategies to alleviate or prevent the progression of PTOA. This protocol describes an open, drop tower-based rabbit femoral condyle impact model to induce cartilage damage. This model delivered peak loads of 579.1 &plusmn; 71.1 N, and peak stresses of 81.9 &plusmn; 10.1 MPa with a time-to-peak load of 2.4 &plusmn; 0.5 ms. Articular cartilage from impacted medial femoral condyles (MFCs) had higher rates of apoptotic cells (p = 0.0058) and possessed higher Osteoarthritis Research Society International (OARSI) scores of 3.38 &plusmn; 1.43 compared to the non-impacted contralateral MFCs (0.56 &plusmn; 0.42), and other cartilage surfaces of the impacted knee (p &lt; 0.0001). No differences in OARSI scores were detected among the non-impacted articular surfaces (p &gt; 0.05).

The open medial femoral condyle impact model in rabbits is reliable for studying post-traumatic osteoarthritis (PTOA) and novel therapeutic strategies to mitigate PTOA progression. This protocol generates an isolated cartilage defect of the posterior medial femoral condyle in rabbits using a carriage-based drop tower with an impactor head.

Post-traumatic osteoarthritis (PTOA) is responsible for 12% of all osteoarthritis cases in the United States. PTOA can be initiated by a single traumatic ...

Therapeutic Potential of Tuina Massage for Knee Osteoarthritis

Tuina Intervention in Sodium Monoiodoacetate Injection-Induced Rat Model of Knee Osteoarthritis

Knee osteoarthritis (KOA), a common degenerative joint disorder, is characterized by chronic pain and disability, which can progress to irreparable structural damage of the joint. Investigations into the link between articular cartilage, muscles, synovium, and other tissues surrounding the knee joint in KOA are of great importance. Currently, managing KOA includes lifestyle modifications, exercise, medication, and surgical interventions; however, the elucidation of the intricate mechanisms underlying KOA-related pain is still lacking. Consequently, KOA pain remains a key clinical challenge and a therapeutic priority. Tuina has been found to have a regulatory effect on the motor, immune, and endocrine systems, prompting the exploration of whether Tuina could alleviate KOA symptoms, caused by the upregulation of inflammatory factors, and further, if the inflammatory factors in skeletal muscle can augment the progression of KOA.
We randomized 32 male Sprague Dawley (SD) rats (180-220 g) into four groups of eight animals each: antiPD-L1+Tuina (group A), model (group B), Tuina (group C), and sham surgery (group D). For groups A, B, and C, we injected 25 &#181;L of sodium monoiodoacetate (MIA) solution (4 mg MIA diluted in 25 &#181;L of sterile saline solution) into the right knee joint cavity, and for group D, the same amount of sterile physiological saline was injected. All the groups were evaluated using the least to most stressful tests (paw mechanical withdrawal threshold, paw withdrawal thermal latency, swelling of the right knee joint, Lequesne MG score, skin temperature) before injection and 2, 9, and 16 days after injection.

Author Spotlight: Treating Knee Osteoarthritis with Tuina - A New Perspective 

This protocol describes the methods of Tuina intervention in sodium monoiodoacetate injection-induced rat model of knee osteoarthritis (KOA), which provides a reference for the application of Tuina in KOA animal models. This protocol also studies the effective mechanism of Tuina for KOA, and the results will help promote its application.

Knee osteoarthritis (KOA), a common degenerative joint disorder, is characterized by chronic pain and disability, which can progress to irreparable ...