The challenge of healing diabetic skin wounds presents a significant hurdle in clinical practice and scientific research. In response to this pressing concern, we have developed a temperature-sensitive, in situ-forming hydrogel comprising poly(n-isopropylacrylamide₁₆₆-co-n-butyl acrylate₉) -poly(ethylene glycol) -poly(n-isopropylacrylamide₁₆₆-co-butyl acrylate₉) copolymer, denoted as PEP, in combination with zinc oxide nanoparticles, forming what we refer to as PEP-ZnO hydrogel. The antimicrobial properties of the PEP-ZnO hydrogel against methicillin-resistant Staphylococcus aureus were rigorously assessed by using the bacteriostatic banding method. In vitro evaluations encompassed examinations of hemocompatibility and biocompatibility. The study further employed a diabetic Sprague-Dawley (SD) rat whole-layer trauma model for comprehensive in vivo analyses. In vivo healing assessments revealed the potential of the PEP-ZnO hydrogel, characterized by increased collagen deposition and enhanced vascularization at the trauma site, thus significantly expediting the healing process. Collectively, these findings endorse the PEP-ZnO hydrogel as a safe and effective dressing for addressing chronic wounds in diabetic patients. This hydrogel not only holds promise for improving the quality of life for diabetic individuals grappling with chronic wounds but also represents a noteworthy advancement in wound care.

Osteoarthritis (OA) is a chronic disease primarily characterized by degenerative changes in articular cartilage and synovitis, for which there are currently no targeted or curative therapies available in clinical practice. In recent years, the in-depth analysis of OA using single-cell sequencing and immunomics technologies has revealed the presence of multiple immune cell subsets, as well as different differentiation states within the same subset, in OA. Through immune-immune and immune-joint tissue interactions, these cells collectively promote or inhibit the progression of arthritis. This complex immune network, where “friends and foes coexist,” has made targeted therapeutic strategies aimed at directly eliminating immune cells challenging, highlighting the urgent need for a detailed review of the composition, distribution, functional heterogeneity, therapeutic potential, and potential risks of immune subsets within the joint. Additionally, the similarities and differences between OA and rheumatoid arthritis (RA) in terms of diagnosis and immunotherapy need to be precisely understood, in order to draw lessons from or reject RA-based immunotherapies. To this end, this review summarizes the major triggers of inflammation in OA, the differentiation characteristics of key immune cell subsets, and compares the similarities and differences between OA and RA in diagnosis and treatment. It also outlines the current immunomodulatory strategies for OA and their limitations. Furthermore, we provide a detailed and focused discussion on immune cells that act as “friends or foes” in arthritis, covering the M1/M2 polarization of macrophages, functional heterogeneity of neutrophils, unique roles of dendritic cells at different maturation states, the balance between pro-inflammatory T cells and regulatory T cells (Tregs), and the diverse functions of B cells, plasma cells, and regulatory B cells (Bregs) in OA. By interpreting the roles of these immune cells, this review clarifies the dynamic changes and interactions of immune cells in OA joints, providing a theoretical foundation for more precise targeted interventions in future clinical practice.

Objective: The objective of this study was to characterize the activation and differentiation of B cells in the synovium of osteoarthritis (OA) and to explore the underlying molecular mechanisms. Methods: Peripheral blood and synovial samples from OA patients at different stages were collected, and flow cytometry was employed to analyze the activation and differentiation of B cells. Immunofluorescence staining of joint synovium from OA mice at different stages was conducted to assess mice joint synovium B cell activation and differentiation. Co-culture experiments of synovial fibroblasts with B cells were performed to investigate the influence of synovial cells on B cell activation and differentiation. Finally, transcriptome analysis was utilized to identify potential key molecules and pathways. Results: In OA patients, the infiltration, activation, and differentiation of B cells in synovium and peripheral blood exhibited distinct characteristics. Specifically, the proportion of activated CD86+ B cells and the differentiation marker HLA-DR+ increased with disease severity, whereas the proportion of the differentiation marker IgM decreased. The proportion of CD38+ B cells also decreased with increasing severity, although this change lacked statistical significance. Immunofluorescence staining of CD19+ and CD86+ cells in mice indicated increased expression with greater OA severity. Co-culture experiments demonstrated that OA synovial fibroblasts promoted B cell activation and differentiation, as evidenced by higher expression levels of CD86+ and HLA-DR+ in the OA group compared to controls. Additionally, the proportion of naive B cells decreased as disease severity progressed. Conclusion: Synovial fibroblasts in OA have been shown to promote the differentiation and activation of B cells, indicating that B cells play a significant role in the pathogenesis of synovium inflammation in OA.

Background: Osteoarthritis (OA) pathogenesis involves age-related immune dysregulation, yet non-invasive diagnostic tools and mechanistic insights remain limited. Methods: We integrated transcriptomic profiling of four OA-affected joint tissues with machine learning to identify potential peripheral blood biomarkers. Weighted gene co-expression network analysis was employed to explore gene modules and pathways associated with OA. Single-cell RNA sequencing was performed on 217 983 joint cells to delineate B cell differentiation trajectories. Flow cytometry was used to validate age-associated B cell imbalances in peripheral blood. Results: We identified five peripheral blood biomarkers: MAPK1, MAP3K8, ING1, LDLR, and NUP153 in distinguishing OA patients from controls (the area under the curve [AUC] = 0.966). Importantly, these markers exhibited age-specific expression profiles; ING1, NUP153, and MAP3K8 were elevated, while MAPK1 was reduced in elderly compared to younger OA patients. A refined predictive model based on these age-specific markers demonstrated superior performance specifically for elderly Knee OA (KOA, AUC: 0.8 vs. 0.7 for younger KOA). These biomarkers correlated with immune cell infiltration and inflammatory cytokines. In osteoarthritic joint tissues, B cells predominantly originated from subchondral bone and synovium. Single-cell analysis identified age-specific B cell differentiation patterns, with elderly KOA patients enriched in an activated B cell cluster (C1). Furthermore, B cells from elderly KOA patients showed altered energy metabolism and increased proportions in peripheral blood, and functionally promoted chondrocyte damage. Conclusion: Our findings establish a novel blood-based diagnostic framework for OA and uncover aging-driven B cell remodeling as a key contributor to elderly OA pathogenesis. These findings offer non-invasive diagnostics and immunomodulatory targets for age-specific OA therapy.