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1.Introduction

Body articulation or joint-related diseases often lead to difficulties in mobility and even

paralysis in some instances, seriously affecting the quality of life in patients. Among various joint-

related diseases, osteoarthritis (OA) is one of the most common degenerative diseases of the

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skeletal system, affecting around 85 million people globally every year . Notably, the articular

cartilage plays a crucial role in the lubrication and protection of the joint. The development of OA

is manifested by the gradual loss of the articular cartilage and the densification of the underlying

subchondral bone, leading to osteophyte formation and subchondral sclerosis, or even chondrocyte

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apoptosis and synovial effusion . Several treatment strategies include the most common joint

replacement surgical procedure, which, however, are sophisticated and complicated and often

suggested at the advanced pathophysiological stage patients. In addition, chemotherapeutic

assistance is provided by prescribing steroids and nonsteroidal anti-inflammatory drugs (NSAIDs)

for OA patients. However, the prescribed medication is just a symptomatic pain relief, which is

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short-lived and transient, requiring long-term therapeutic strategies for OA therapy . Moreover, it

should be noted that most of the currently available drug candidates are still lethargic. Hence,

extensive research has been conducted to develop highly efficient, cost-effective, and non-invasive

treatment strategies for OA therapy 9,10 .

Moreover, it is inevitable to establish screening models for the rapid development of

chemotherapeutic drugs. In this vein, highly efficient preclinical models are required to achieve

high-throughput drug screening and enable precise and accurate investigation of OA pathology 11-

13 . There exist several in vivo models of replicating OA disorder with nearly clinically relevant

features. However, these models suffer from several limitations of cost, long period for model

development, and handling challenges. Numerous in vitro models have been developed to address

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