Regenerative methods in osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, which is characterized by anatomical and physiological changes such as cartilage degradation, bone remodeling, osteophyte formation, joint inflammation, and loss of joint function [[1], [2], [3], [4]]. With the entire joint being affected, the main affected structure in OA is the articular cartilage [5]. Due to the aneural and avascular nature of the cartilage, it has a low regenerative capacity and therefore limited repair potential of the joint [6]. Pain, limitation of joint movement, and decreased function in OA seriously reduce the quality of life of patients [7]. Because of the high prevalence of OA worldwide, the medical resources and socioeconomic costs associated with its treatment and management are constantly increasing [8,9].

Despite the socioeconomic impact of OA, the treatment options available to OA patients today are quite limited, and therapeutic approaches are mostly in the form of symptom control. For this purpose, various methods are applied to alleviate the patient's symptoms and reduce the progression of the degenerative process [10]. Self-management programs, pharmacologic therapies, thermal therapies, exercises, intra-articular (IA) injection treatments such as steroids and hyaluronic acid (HA), and surgical treatment methods are among the main methods used in treatment [11].

The growing understanding of the pathogenesis of OA, particularly the role of cytokines, growth factors, and signaling molecules, has opened up new perspectives for cartilage repair and treatment [12]. Because conventional management options are ineffective, current research focuses on identifying biological pathways that cause changes in joint homeostasis and accelerate joint healing [13]. Tissue engineering and regenerative strategies based on biomaterials, cells, and other bioactive molecules have emerged as possibilities for osteoarthritis cartilage repair [14]. The most commonly used restorative methods to treat cartilage defects are stem cell and platelet-rich plasma (PRP) injections, chondrocyte transplantation, or surgical procedures such as microfracture and autologous chondrocyte implantation (ACI) [15,16].

Surgically applied approaches such as ACI and microfracture have some limitations. ACI has variable success and is associated with complications such as inadequate fusion, delamination, and graft failure [14,17,18]. The widespread joint involvement and the inflammatory environment in OA also do not make ACI a viable option [19,20]. In the osteoarthritic environment, implanted chondrocytes may undergo undesirable differentiation or apoptosis, affecting treatment efficacy, besides long-term data on ACI are still limited [21,22]. The quality of cartilage repair performed by the microfracture (MF) method, which is often used for cartilage regeneration in OA, is also variable and inconsistent [[23], [24], [25]]. The ‘fibrocartilage’ that occurs after the MF operation has significantly reduced mechanical properties compared to normal articular cartilage [26].

Due to the limitations of current treatment approaches to address OA, there has been significant interest in cell-based therapies for cartilage regeneration in recent years [27]. Regenerative medicine is a rapidly developing technology that allows the repair, and regeneration of damaged and diseased cells, tissues, and organs of the body [28]. Cell therapy is the insertion of cells into damaged tissue in order to reconstruct cell function, and tissue engineering is the application of cells with a three-dimensional tissue scaffold to create a tissue-like structure for the repair of dysfunctional tissue or organ [29]. In this article, mainly cell-based therapies will be discussed.

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