Bioactive Calcium Hydride-Driving "Triple" Hydrogen/Alkaline/Calcium Therapy for Efficient Treatment of Osteomyelitis.

Osteomyelitis with high mortality and disability rates is a common clinical disease caused by a bacterial infection that is difficult to cure. Considering the stubborn nature and depth of tissue infection, rapid and effective treatments for osteomyelitis remain an enormous challenge. Calcium hydride (CaH2), as efficient hydrogen/alkaline/calcium donors, is employed for combined osteomyelitis therapy. CaH2 reacts with water to sufficiently generate a strong alkali environment with hydroxide anions (OH-) to inhibit bacterial proliferation and induce bacterial death. The released calcium ions (Ca2+) induce calcium overload to kill bacteria first and then serves as calcium source to promote new bone formation. Another byproduct, hydrogen enhances the bacterial membrane permeability and scavenges excess reactive oxygen species (ROS). After incubation with bacteria, CaH2 significantly increases the permeability of the bacterial membrane, therefore increasing the entry of OH- and Ca2+ into bacterial cells, thereby leading to significant bacterial death. After being applied to S. aureus-infected mouse tibia osteomyelitis, CaH2 materials efficiently kill bacteria, relieve local inflammation, and promote new bone formation in a short time. Overall, bioactive metal hydride-associated "triple" hydrogen/alkaline/calcium therapy provides a new idea for the treatment of deep-site bacterial infection, which is beneficial for relieving the pressure caused by antibiotic-resistant bacteria.

Autocatalytic bifunctional supramolecular hydrogels for osteoporotic bone repair.

Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce-Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce-Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce-Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid (RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling, hypoxia metabolism and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce-Aln gel. In vivo experiments showed that the clinical drug-based Ce-Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.

Magnesium implants with alternating magnetic field-enhanced hydrogen release and proton depletion for anti-infection treatment and tissue repair.

Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H2 gas and ions (OH- and Mg2+) for the treatment of osteomyelitis. H2 released by Mg rods under AMFs effectively scavenged cytotoxic ROS, exhibiting anti-inflammatory effects and consequently disrupting the environment of bacterial infections. In addition, the OH- hindered the energy metabolism of bacteria by effectively neutralizing protons within the microenvironment. Moreover, H2 impaired the permeability of bacterial membranes and expedited the damage induced by OH-. This synergistic AMF-induced H2 and proton depletion treatment approach not only killed both gram-negative and gram-positive bacteria but also effectively treated bacterial infections (abscesses and osteomyelitis). Moreover, Mg2+ released from the Mg rods enhanced and accelerated the process of bone osteogenesis. Overall, our work cleverly exploited the eddy-thermal effect and chemical activity of Mg implants under AMFs, aiming to eliminate the inflammatory environment and combat bacterial infections by the simultaneous release of H2, OH-, and Mg2+, thereby facilitating tissue regeneration. This therapeutic strategy achieved multiple benefits in one, thus presenting a promising avenue for clinical application.

Lead Isolation and Capture in Perovskite Photovoltaics toward Eco-Friendly Commercialization.

Perovskite solar cells (PSCs) are developed rapidly in efficiency and stability in recent years, which can compete with silicon solar cells. However, an important obstacle to the commercialization of PSCs is the toxicity of lead ions (Pb2+) from water-soluble perovskites. The entry of free Pb2+ into organisms can cause severe harm to humans, such as blood lead poisoning, organ failure, etc. Therefore, this work reports a "lead isolation-capture" dual detoxification strategy with calcium disodium edetate (EDTA Na-Ca), which can inhibit lead leakage from PSCs under extreme conditions. More importantly, leaked lead exists in a nontoxic aggregation state chelated by EDTA. For the first time, in vivo experiments are conducted in mice to systematically prove that this material has a significant inhibitory effect on the toxicity of perovskites. In addition, this strategy can further enhance device performance, enabling the optimized devices to achieve an impressive power conversion efficiency (PCE) of 25.19%. This innovative strategy is a major breakthrough in the research on the prevention of lead toxicity in PSCs.

Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis.

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

The combination of eddy thermal effect of biodegradable magnesium with immune checkpoint blockade shows enhanced efficacy against osteosarcoma.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

Oxygen-Deficient Molybdenum Oxide Nanosensitizers for Ultrasound-Enhanced Cancer Metalloimmunotherapy.

Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability for US-triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX -PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX -PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS-STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX -PEG, the combination treatment of MoOX -triggered SDT and aCTLA-4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors.

HX V2 O5 Nanocatalysts Combined with Ultrasound for Triple Amplification of Oxidative Stress to Enhance Cancer Catalytic Therapy.

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)-mediated cancer therapy. Herein, vanadium-based nanocatalysts, hydrogen vanadium bronzes (HX V2 O5 , for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi-functional catalytic activity in decomposing H2 O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS-mediated cancer therapies.