## 1 Introduction  
Wound healing is a complicated biological process consisting of a coordinated series of cellular and molecular activities to restore tissue integrity and function following an injury [1]. The wound-healing process is uniquely challenged in the oral cavity, particularly within gingival tissues, by constant microbial exposure and mechanical stress, presenting clinical hurdles for successful outcomes in periodontal surgery and implant therapy [2]. Human gingival fibroblasts (HGnFs) play a key role in this process by producing extracellular matrix, inflammation regulation and tissue remodeling [3,4].  
A major challenge in the management of periodontal wounds is the equilibrium between infection control and tissue regeneration. Conventional antiseptics, such as chlorhydine gluconate, are commonly utilized for their antibacterial qualities; nevertheless, their cytotoxic effects on fibroblasts and other oral cells might compromise fibroblast viability and potentially impede wound healing [5,6]. Consequently, there is an increasing demand for alternative strategies to manage infection and support cellular health and regenerative potential.  
Recently, oxygen-based therapies have gained interest in regenerative medicine due to oxygen's critical role in cellular metabolism and wound-healing phases, such as hemostasis, inflammation, proliferation and remodeling [7, 8, 9]. In the initial stages of wound healing, oxygen supports immune defense through oxidative bursts, while in later phases, it stimulates fibroblast proliferation, collagen synthesis, angiogenesis and matrix maturation [10,11]. Topical oxygen therapy, which refers to the direct application of oxygen onto the wound surface, may overcome local hypoxia associated with gingival inflammation and microvascular impairment [12, 13, 14]. Oxygen facilitates gingival repair by improving microcirculation and fostering tissue regeneration [14]. Furthermore, this method allows for controlled delivery with potentially fewer systemic side effects.  
Oxygen fluid (blue(r)m), a stable oxygen-releasing liquid formulation, is one of the emerging topical oxygen therapy methods that has the potential to promote oral wound healing. This is due to its simplicity of application and the potential for consistent coverage [7, 8, 9]. However, data on its biological impact on gingival fibroblasts remain limited. Preliminary studies in other cell types and tissue models suggest dose-dependent effects, wherein sub-inhibitory doses may preserve or enhance wound-healing functions, underlining the importance of dose optimization for periodontal applications [10,15].  
The wound-healing process is complicated by oxidative stress. Reactive oxygen species (ROS) can be elevated by excessive oxygen, which can lead to oxidative stress and the impedance of cellular processes [16]. Excessive ROS may induce apoptosis and chronic inflammation, whereas physiological ROS levels facilitate signaling for cell migration and proliferation [16,17].  
In addition to oxidative stress, the healing process is significantly influenced by the modulation of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-\(\alpha\)), as well as enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) [18, 19, 20, 21]. Therefore, it is imperative to comprehend the influence of these factors on gingival fibroblasts in order to evaluate the clinical viability of topical oxygen fluid.  
This study aimed to evaluate the impact of oxygen fluid (blue(r)m) at varying concentrations on the cellular expression of inflammatory mediators, oxidative stress, HGnF viability and proliferation. This study attempted to address a critical lacuna in periodontal regenerative research.