Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation and progressive bone destruction. Transcriptomic profiling identified hyperactivated B cells as key contributors to osteoimmune dysregulation, supporting localized B cell intervention as a therapeutic strategy. Here, an injectable thermosensitive hydroxypropyl chitin hydrogel incorporating Cu/Zn-doped bioactive glass particles, termed BG@HPCH, was developed for localized metalloimmunotherapy. BG incorporation improved the shear-thinning behavior, thermosensitive gelation, storage modulus, and stability of the hydrogel. In vitro, ionic release from BG@HPCH selectively reduced pathogenic B cell survival while preserving mesenchymal stem cell (MSC) viability. The optimized M-BG@HPCH increased the B cell dead-cell area from 1.93 ± 0.48% to 91.12 ± 0.90% at 24 h, while maintaining MSC viability at 98.59 ± 0.26% after 3 days. In TNF-transgenic mice, a single intra-articular injection of BG@HPCH reduced arthritis index scores from 2.88 ± 0.18 to 1.81 ± 0.13 at day 28, limited bone erosion, and showed no detectable systemic toxicity. Micro-CT analysis showed improved bone preservation, with BV/TV increasing from 30.00 ± 6.74% to 55.66 ± 1.07%. OCN staining further confirmed enhanced osteogenic activity, with the OCN+ area increasing by 2.16 times. Flow cytometry confirmed reduced B220+CD45.2+ B cell accumulation in treated joints. Single-cell RNA sequencing of 23,921 joint cells showed that BG@HPCH reduced inflammatory B cell, macrophage, and fibroblast subsets while expanding osteoblast-associated regenerative populations, accompanied by suppression of CD23− and CD74-associated B cell signaling axes. These findings establish BG@HPCH as a localized immunoregenerative biomaterial for coordinating pathogenic B cell depletion and bone repair in RA.
Intervertebral disc degeneration (IVDD) represents a leading cause of chronic low back pain worldwide, imposing considerable public health and socioeconomic burdens. Current clinical interventions remain largely palliative, unable to reverse the progressive pathological cascade. This cascade is driven by a core self-amplifying triad of oxidative stress, chronic inflammation, and nutrient deprivation within the unique avascular, high-load disc niche, and ultimately progresses to end-stage terminal phenotypes such as biomechanical failure and neurovascular ingrowth. Over recent years, biomaterial-based regenerative strategies have evolved from passive structural fillers toward multifunctional platforms capable of active microenvironmental reprogramming. This review provides a systematic, critical synthesis of state-of-the-art advances in the field, organized within a hierarchical framework spanning immunometabolic modulation of the degenerative niche and targeted delivery of cellular and molecular therapeutics with further elaboration of precision-stratified design and whole-disc tissue engineering. We critically appraise evidence maturity across different strategy classes and dissect disc-specific translational barriers, noting that most candidate platforms remain at preclinical validation stages. Building on this analysis, we outline priority research directions and realistic near-term translational milestones to guide rational development of next-generation regenerative platforms toward durable functional disc repair.
Metal-ion-mediated lethal pathways offers a highly potent strategy for antibacterial treatments. However, relying on single-pathway mechanisms often fails to overwhelm bacterial antioxidant defenses, reducing antibacterial efficacy. This study designed a heterojunction nanozyme (Cu2O/Fe2O3) that induces ferroptosis-like death and copper-mediated metabolic toxicity exhibiting cuproptosis-like features, achieving highly effective antibacterial treatment. Computational chemistry analysis indicates that the Cu2O/Fe2O3 heterointerface establishes a built-in electric field through spontaneous interfacial electron transfer, thereby enhancing its peroxidase (POD)-like activity. Within the acidic bacterial microenvironment, Cu2O/Fe2O3 catalyzes the generation of large amounts of reactive oxygen species (ROS) and releases metal ions, inducing and amplifying ferroptosis-like death, which disrupts the function of ETC enzymes by attacking iron–sulfur clusters. Concurrently, copper ions disrupt the redox balance by depleting bacillithiol (BSH), indirectly increasing bacterial susceptibility and promoting ferroptosis-like death. Furthermore, the accumulation of copper ions triggers severe metabolic impairments that biochemically resemble the cuproptosis cascade, which disrupts key enzymes of the TCA cycle and impairs the synthesis of electron donors (NADH and FADH2), thereby cutting off the supply of substrates to ETC at the upstream stage. Overall, this study demonstrates that triggering bimetallic ion-mediated metabolic disruptions induces an energy crisis in bacteria, providing a reference for multimodal antibacterial strategies.
Retinal vein occlusion (RVO) causes retinal ischemia, macular edema, and vision loss, yet current anti-vascular endothelial growth factor (anti-VEGF) therapies primarily limit vascular leakage and leave ischemia-driven neuroinflammation insufficiently controlled. Here, we reveal a critical role for microglia-associated NLRP3–IL-18 signaling in amplifying inflammation during early RVO. Bulk retinal RNA sequencing showed broad innate immune activation, whereas single-cell transcriptomic profiling and spatial protein analysis identified prominent inflammasome-related changes in retinal microglia. Constitutive global deletion of Nlrp3 or Il18 attenuated microglial activation and preserved retinal structure and electrophysiological function. To translate this mechanistic insight into a targeted anti-inflammatory strategy, we engineered MG1-functionalized, MCC950-loaded nanoliposomes for microglia-targeted NLRP3 inhibition. MG1 functionalization promoted preferential nanoparticle uptake by activated microglia and suppressed NLRP3–IL-18 signaling more effectively than free MCC950 or non-targeted nanoliposomes. In experimental RVO, a single intravitreal dose administered 6 h after induction alleviated retinal inflammation and edema while preserving retinal electrophysiological responses. These findings establish microglia-associated NLRP3–IL-18 signaling as a therapeutic target in early RVO and support MG1-MCC950 nanoliposomes as a bioactive nanotherapeutic platform for RVO.
Electrospun nanofibers (ESNFs) have become a major focus of modern research given their adaptable architecture, extensive interface, and distinctive physicochemical characteristics, making them appropriate for varied applications such as catalysis and environmental cleanup, drug delivery (DD), tissue engineering (TE), sensing, actuation, and various energy-related technologies. As a result, electrospinning (ES) has emerged as a versatile manufacturing technique, driving intensive efforts to engineer nanofibrous structures specifically for biomedical purposes. Functionalization of ESNFs can be achieved by embedding functional agents or altering surface chemistry to introduce specific functionalities. This review discusses the fabrication methods, optimization techniques, and broad biomedical applications of modified ESNFs, emphasizing their key properties, including biocompatibility, degradability, and safety profile. The article outlines various strategies for creating and modifying ESNFs, followed by a comprehensive analysis of their applications in tissue regeneration, DD, wound repair, antimicrobial therapy, cancer diagnostics and treatment, and biosensing. By critically evaluating recent advances, highlighting future directions, and addressing ongoing challenges about ES, this review underscores the transformative potential of functionalized ESNFs as efficient and adaptable biomaterials for biomedical technologies.
