Polyhydroxyalkanoates (PHAs) are storage granules found in bacteria that are essentially hydroxy fatty acid polyesters. PHA molecules appear in variety of structures, and amongst all types of PHAs, polyhydroxybutyrate (PHB) is used in versatile fields as it is a biodegradable, biocompatible, and ecologically safe thermoplastic. The unique physicochemical characteristics of these PHAs have made them applicable in nanotechnology, tissue engineering, and other biomedical applications. In this review, the optimization, extraction, and characterization of PHAs are described. Their production and application in nanotechnology are also portrayed in this review, and the precise and various production methods of PHA-based nanoparticles, such as emulsion solvent diffusion, nanoprecipitation, and dialysis are discussed. The characterization techniques such as UV-Vis, FTIR, SEM, Zeta Potential, and XRD are also elaborated.

Osteoarthritis (OA) is a low-grade inflammatory disorder of the joints that causes deterioration of the cartilage, bone remodeling, formation of osteophytes, meniscal damage, and synovial inflammation (synovitis). The synovium is the primary site of inflammation in OA and is frequently characterized by hyperplasia of the synovial lining and infiltration of inflammatory cells, primarily macrophages. Macrophages play a crucial role in the early inflammatory response through the production of several inflammatory cytokines, chemokines, growth factors, and proteinases. These pro-inflammatory mediators are activators of numerous signaling pathways that trigger other cytokines to further recruit more macrophages to the joint, ultimately leading to pain and disease progression. Very few therapeutic alternatives are available for treating inflammation in OA due to the condition’s low self-healing capacity and the lack of clear diagnostic biomarkers. In this review, we opted to explore the immunomodulatory properties of mesenchymal stem cells (MSCs) and their paracrine mediators-dependent as a therapeutic intervention for OA, with a primary focus on the practicality of polarizing macrophages as suppression of M1 macrophages and enhancement of M2 macrophages can significantly reduce OA symptoms.

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin−1β (IL−1β) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL−1β induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease.

Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by cartilage degeneration and synovial inflammation. Paracrine interactions between chondrocytes and macrophages play an essential role in the onset and progression of OA. In this study, in replicating the inflammatory response during OA pathogenesis, chondrocytes were treated with interleukin-1β (IL-1β), and macrophages were treated with lipopolysaccharide and interferon-γ. In addition, a coculture system was developed to simulate the biological situation in the joint. In this study, we examined the impact of hyaluronic acid (HA) viscosupplement, particularly Hyruan Plus, on chondrocytes and macrophages. Notably, this viscosupplement has demonstrated promising outcomes in reducing inflammation; however, the underlying mechanism of action remains elusive. The viscosupplement attenuated inflammation, showing an inhibitory effect on nitric oxide production, downregulating proinflammatory cytokines such as matrix metalloproteinases (MMP13 and MMP3), and upregulating the expression levels of type II collagen and aggrecan in chondrocytes. HA also reduced the expression level of inflammatory cytokines such as IL-1β, TNF-α, and IL-6 in macrophages, and HA exerted an overall protective effect by partially suppressing the MAPK pathway in chondrocytes and p65/NF-κB signaling in macrophages. Therefore, HA shows potential as a viscosupplement for treating arthritic joints.

Inflammatory disorders encompass a range of conditions, including osteoarthritis (OA), characterized by the body’s heightened immune response to diverse stimuli. OA is a prevalent degenerative joint disease characterized by the progressive deterioration of joint cartilage and subchondral bone, leading to pain, limited mobility, and physical disability. Synovitis, the inflammation of the synovial membrane, is increasingly recognized as a critical factor in OA pathogenesis and progression. This study evaluates the therapeutic potential of cinnamaldehyde (CA), a bioactive compound derived from cinnamon, on synovial and articular inflammation in OA. Given CA’s established anti-inflammatory, antioxidant, and antibacterial properties, this research explores its specific impact on OA and synovitis. The cytotoxicity of CA was assessed using a CCK-8 assay in human IL-1β pretreated chondrocytes and synoviocytes, which serve as in vitro models of OA and synovitis. The study further examined the effects of CA on the expression of proinflammatory cytokines, including IL-6, COX-2, and TNF-α, utilizing multiple analytical techniques. Additionally, the production of matrix metalloproteinases (MMP-3 and MMP-13) and the activation of the NF-κB signaling pathway, particularly the phosphorylation of p65 (pp65), were investigated. The role of the NF-κB inhibitor 5HPP-33 and its downstream effects on gene expression, including COX-2 and IL-6, as well as the MAPK pathway components (p38, ERK, and JNK), were also explored. An MEK inhibitor (U0126) was employed to assess its downstream impact on COX-2 and IL-6 expressions. The results demonstrated that CA significantly inhibited the expression of proinflammatory cytokines and suppressed NF-κB activation in IL-1β pretreated chondrocytes and synoviocytes. These findings suggest that CA, in a dose-dependent manner, may serve as an effective therapeutic agent for preventing OA and synovitis, offering valuable insights into its potential role in managing synovial inflammation and OA.