Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory joint disease [1], affecting approximately 5 in every 1000 individuals and leading to significant joint damage and disability [2]. While RA can involve multiple organs and tissues, its primary impact is on the joints, where it causes inflammatory synovitis. This condition often results in articular cartilage degradation and the infiltration and proliferation of synovial tissue within the joints [3]. If left untreated, the inflammatory process becomes chronic, with recurrent flare-ups that may persist for days, months, or even years [4]. The indirect costs of RA, primarily due to lost work capacity, are estimated to be nearly three times higher than the direct costs of treatment [5].

Despite significant medical advancements, the precise etiology of RA remains unclear. However, in recent decades, inflammatory processes, pathophysiology, and both genetic and autoimmune factors—particularly at sites of inflammation and infection—have been identified as key contributors [6]. These factors activate immune cells, including monocytes, synovial fibroblasts, and macrophages, which in turn stimulate antigen-specific T-helper (CD4+ T) cells [7]. The primary mediators of RA, such as interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-α), are released following CD4+ T-cell activation [8,9]. Additionally, B cells are stimulated to produce antibodies against citrullinated proteins. Notably, anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) can be detected in individuals up to a decade before the onset of clinical symptoms [10,11].

Rheumatoid factor (RF), the first identified biomarker for RA, consists of antibodies that target the crystallizable fragment (Fc) region of IgG [12]. Its sensitivity in detecting RA ranges from 41 to 66 % in the early stages of the disease and from 62 to 87 % in more advanced cases [13]. The complex interactions among various effector cells and cytokines contribute to joint damage in the synovial membrane and articular tissues [14]. Additionally, oxidative stress and inflammation are believed to play a significant role in RA pathophysiology, as evidenced by elevated oxidative stress markers and decreased antioxidant levels in RA patients [15,16].

Currently, a wide range of treatment options is available for RA, encompassing both symptomatic and disease-modifying approaches. Symptomatic treatments include nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs), which help manage inflammation and alleviate symptoms. In contrast, disease-modifying strategies aim to alter the disease course using disease-modifying antirheumatic drugs (DMARDs), which are classified into conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs. These therapies suppress autoimmune responses and slow or prevent joint degeneration [17]. However, despite significant research expanding treatment options, many RA patients experience limited therapeutic efficacy or adverse side effects [18]. Therefore, our objective is to develop a treatment capable of regenerating the tissues and cartilage damaged by RA. This approach seeks not only to alleviate pain and halt further tissue destruction but also to actively restore damaged structures while minimizing the side effects associated with current therapies.

Numerous studies have demonstrated the beneficial effects of laser therapy in promoting bone regeneration [19]. These lasers function without generating heat, utilizing emission spectra ranging from red to near-infrared and operating at powers below 500 mW [20]. Since 1981, low-level laser therapy (LLLT) has been employed in clinical settings to treat inflammatory disorders [21], effectively reducing swelling [22], alleviating inflammation [23], and providing pain relief [24]. Consequently, low-intensity laser therapy is commonly recommended as part of physical therapy protocols for arthritis management [25]. However, the application of femtosecond lasers in this context is not established.

A femtosecond laser (FSL) is a specialized laser that emits ultra-short pulses of light, each lasting just one femtosecond (10−15 s) [19]. This places it within the category of ultrashort-pulsed lasers, which also includes picosecond lasers. These rapid pulses are typically generated through passive mode-locking [26]. The extremely short duration of FSL pulses minimizes shock waves, allows for highly focused micrometer-scale targeting, and prevents thermal buildup, thereby reducing collateral damage to surrounding tissues [27]. Research has shown that femtosecond laser irradiation at wave lengths of 380, 400, 420, and 440 nm significantly inhibits T47D breast cancer cell growth, with 400 nm exhibiting the strongest effect [28]. However, there is no current research supporting the use of FSL in treating RA. Thus, in our study, we aimed to investigate the therapeutic efficacy of femtosecond laser, at a wavelength of 830 nm, on a rheumatoid arthritis rat model by detecting its antioxidant, anti-inflammatory, and regenerative effects on the histological features of the ankle.