Allergic rhinitis (AR) has gained an increasing prevalence over the years, a more effective and safe treatment strategy need to be carried out. Hypoxia induced Mesenchymal stem cell derived extracellular vesicles (hEVs) have shown great therapeutic potential for AR, however, their low bioavailability through systemic administration decreased efficacy in clinical application. In the current study, an MXene-modified GelMA hydrogel was developed as a sustained release platform for hEVs. The hEVs-loaded MXene-modified GelMA hydrogel (hEVs@M-GelMA hydrogel) we prepared had rich porous structure, good hydrophilicity, biocompatibility and antibacterial properties, and showed significant inhibitory effect on the generation of reactive oxygen species in vitro. By using AR mice model, we verified that hEVs@M-GelMA hydrogel significantly alleviated AR symptoms, reduced local eosinophil infiltration, inhibited the intensity of nasal oxidative stress response, suppressed the production of OVA-sIgE in blood, decreased IL-4 secretion and promoted IL-10 and IFN-γ expression. This study provides a novel delivery platform for MSC-EVs-based AR therapy.

The pathological microenvironment in diabetic wounds is delineated by heightened inflammatory responses and persistent proinflammatory macrophage activity, which significantly hinders the wound healing process. Exogenous electrical stimulation (ES), by modulating the electric field distribution in wounds, has shown significant potential in treating inflammatory wounds. However, this approach relies on additional power sources and complex circuit designs. Here, a bionic neuro-immuno-regulatory (BNIR) system was proposed for reshaping the endogenous electric fields (EFs) through collecting ion flow. The BNIR system comprises microporous structure scaffolds and nanosheets, enabling swift biofluid collection and electrical signal transmission, with the ability to promote cell proliferation and migration and exhibit antioxidant properties. More importantly, the BNIR system induced the transition of M1 macrophages to M2 macrophages through neuro-immuno-regulatory. In diabetic rat skin wounds, the BNIR system significantly enhanced healing by simultaneously neuro-immuno-regulatory, promoting angiogenesis, scavenging ROS, and facilitating tissue remodeling. This work aims to advance the development of a bionic system for electrosensitive tissue repair.

Intestinal stem cells (ISCs) engage in proliferation to maintain a stable stem cell population and differentiate into functional epithelial subpopulations. This intricate process is upheld by various signals derived from the host and gut microbiota, establishing an ISC niche. However, during inflammatory bowel disease (IBD), this signaling niche undergoes dramatic changes, leading to impaired ISC and hindered restoration of the damaged intestinal epithelial barrier. This study introduces intestinal inflammatory microenvironment-responsive microsphere vehicles designed to remodel the ISC niche, offering an approach to treat IBD. Using an advanced emulsion technique, these microsphere vehicles specifically target colonic inflammation sites, delivering a responsive release of MXene and l-arginine. This delivery system is formulated to modulate intestinal flora and immune responses effectively. l-arginine is converted into nitric oxide to regulate the gut microbiome, while MXene serves as a nanoimmunomodulator to stabilize immune homeostasis. Our findings demonstrate that the anti-inflammatory properties of the microspheres are key to promoting epithelial repair and remodeling of the ISC niche. This study highlights the role of antioxidant microspheres as anti-inflammatory agents that indirectly support ISC function and gut regeneration.

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(TiCT) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(TiCT) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN' enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.

Human insulin (HI) fibrillation is a critical event in type II diabetes (T2D), and studying its disaggregation mechanism is an attractive strategy for treating this condition. Here we loaded quercetin onto niobium carbide (NbC), a type of MXene, to create NbC@QUE, which was shown in vitro to disaggregate HI fibrils rapidly. NbC@QUE binds and disaggregates HI fibrils in two stages within a short time frame, converting the highly ordered β-sheet structures into α-helix and random coil. Isothermal titration calorimetry (ITC) was used to determine the thermodynamic parameters of the entire system, revealing that the binding of NbC@QUE to HI fibrils occurs in two stages. Corresponding rapid fluorescence kinetics results demonstrated that NbC@QUE binds with HI monomers or fibrils at a second-level rate, with no intermediates formed during this process. Due to its excellent ability to eliminate reactive oxygen and nitrogen species (RONS), NbC@QUE also has the potential to act as a nanozyme (MXenzyme) to mitigate inflammation caused by HI fibrils, overcoming the limitations of traditional single-protein disaggregation agents. These findings provide insights into the mechanism of protein fibril disaggregation from a physicochemical perspective and offer guidance for designing multifunctional materials for protein fibril disaggregation and decomposition.

Atherosclerosis (AS), marked by lipid buildup and chronic inflammation in arteries, leads to major cardiovascular events. Macrophages contribute to AS by engulfing low-density lipoproteins, forming foam cells, and driving inflammation that promotes plaque growth and instability. The emerging piezocatalytic therapy uses piezoelectric materials to generate radicals that target inflammation-related macrophages for AS treatment, but the conventional materials suffer from low radical yield, substantially limiting clinical use. In this study, the construction of piezoelectric BaTiO/TaC MXene heterostructured nanosheets (BTOMX NSs) is reported for achieving enhanced piezoelectric AS treatment by blocking early atherosclerotic plaque progression. The composite BTOMX NSs feature high electron-hole separation efficiency due to their narrowed bandgap and high surface potential under ultrasound irradiation, enabling more effective radical generation by piezocatalytic effects. Especially, these biocompatible piezoelectric nanosheets accumulate in plaques and are efficiently internalized by macrophages, where they generate radicals under ultrasound stimulation, ultimately triggering macrophage apoptosis and interrupting plaque progression. In ApoE mice, the BTOMX NSs remove lesional macrophages, reduce lipid accumulation, and mitigate inflammation, decreasing plaque burden from 21.42% to 9.04%. Taken together, this work provides a paradigm for enhancing BaTiO-based piezocatalytic performance by heterostructure construction, demonstrating an efficient, noninvasive, and safe therapeutic approach for treating early-stage AS.

Diabetic wounds are highly prone to persistent pathogenic infections due to the complex nature of their microenvironment, which significantly hinders the healing process under hyperglycemic conditions. In this study, we developed a bio-heterojunction enzyme system consisting of hollow CeO/TiCT MXene quantum dots (CeO@MQD) integrated with glucose oxidase (GOx-CeO@MQD). The GOx-CeO@MQD system exhibits multifunctional enzymatic activities, including peroxidase (POD) and catalase (CAT)-like activity, resulting in the production of •OH and O, alongside the consumption of glucose and glutathione (GSH). The incorporation of GOx effectively mitigates the hyperglycemic microenvironment by catalyzing glucose, leading to a significant increase in HO production, which is subsequently converted into bactericidal •OH through POD activity. Furthermore, HO can be catalyzed into HO and O via the CAT pathway, thereby alleviating inflammation caused by the excessive accumulation of reactive oxygen species. In vitro antibacterial assays demonstrated that the GOx-CeO@MQD system achieved remarkable bactericidal efficiencies of 99.99% against E. coli and S. aureus at concentrations of 12.5 ppm and 2.0 ppm, respectively. In vivo experiments further revealed that GOx-CeO@MQD significantly promoted angiogenesis, accelerated wound epithelialization, and induced a strong anti-inflammatory response, thus facilitating the regeneration of infected diabetic skin. This study proposes a novel approach for diabetic wound treatment by harnessing the synergistic effects of multiple enzyme-like activities.

Bacterial prostatitis represents a specific form of prostatitis, primarily resulting from bacterial infection and significantly impairing the life quality of patients. In this paper, we respond to the inability of conventional drugs to simultaneously address both bacterial infection and oxidative stress in the treatment of prostatitis by designing a multifunctional nanoparticle, called QM (Cu) NPs, with dual functionality. QM (Cu) NPs have the capacity to generate reactive oxygen radicals to eradicate bacteria under the influence of laser irradiation. Additionally, they are capable of rapidly scavenging the surplus free radicals, thereby restoring the intracellular redox homeostasis in the absence of laser illumination. A comprehensive characterization of QM (Cu) NPs was conducted, followed by an in-depth analysis of their effects on cells. The therapeutic efficacy of QM (Cu) NPs in multimodal treating bacterial prostatitis was then demonstrated. Furthermore, the outcomes of transcriptomic and molecular biology experiments indicated that QM (Cu) NPs markedly regulate the NF-κB p65 and Nrf2-Keap1 signaling pathways, thereby influencing inflammatory and oxidative stress processes. In conclusion, QM (Cu) NPs simultaneously addressed the dual challenges of antibacterial and antioxidant properties, thereby underscoring their potential clinical applications in the treatment of bacterial prostatitis.

In the field of large-area trauma flap transplantation, preventing avascular necrosis remains a critical challenge. Key mechanisms for improving flap viability include angiogenesis promotion, oxidative stress inhibition, and cell death prevention. Recently, two-dimensional ultrathin TiCT (MXene) nanosheets have gained attention for their potential contributions to these processes, though MXene's physiological impact on flap survival had not been previously investigated. This study is the first to confirm MXene's biological effects on the ischaemic microenvironment post-skin flap transplantation. Findings indicated that MXene significantly decreased the necrotic area in ischaemic flaps (37.96% ± 2.00%), with reductions of 30.40% ± 1.86% at 1 mg/mL and 20.19% ± 2.11% at 2 mg/mL in a concentration-dependent manner. Mechanistically, MXene facilitated in situ angiogenesis, mitigated oxidative stress, suppressed pro-inflammatory pyroptosis, and activated the PI3K-Akt pathway, particularly influencing vascular endothelial cells. Comparative transcriptome analysis of skin tissues with and without MXene treatment provided additional evidence, highlighting mechanisms such as pro-inflammatory pyroptosis, ROS metabolic processes, endothelial cell proliferation regulation, and PI3K-Akt signaling pathway activation. Overall, MXene demonstrated biological activity, effectively promoting ischaemic flaps survival and presenting a novel strategy for addressing ischaemic necrosis in skin flaps.

Knee Osteoarthritis (OA) is prevalent in older adults which eventually lead to disability. Current treatment only alleviates symptoms but does not cure the disease. Herein, we implanted MoTiC MXene gelatin-chitosan hydrogels into the osteoarthritis knee joint in mice and treated with 808 nm laser radiation. We investigated MXene hydrogel structure and near infrared radiation (NIR) effect on cell biocompatibility, cartilage matrix synthesis, reactive oxygen species (ROS)production and inflammation in vitro. In vivo anterior cruciate ligament transection (ACLT) OA model treated with MXene hydrogel and NIR exhibits delayed osteoarthritis progression with fewer osteophyte and wider articular space, reduced cartilage lesion, lower Osteoarthritis Research Society International (OARSI) score, higher glycosaminoglycan (GAG) content, higher number of aggrecan and col-II positive cells. MoTiC MXene hydrogel with NIR reduced M1 macrophage related IL-1β and IL-6, increased M2 macrophage related TGF-β and IL-10 in cartilage in OA. MoTiC MXene hydrogel with NIR attenuated ROS and chondrocytes apoptosis in vivo. MoTiC MXene hydrogel may provide a new strategy in treatment of OA.

Immune-mediated bone regeneration driven by bone biomaterials offers a therapeutic strategy for repairing bone defects. Among 2D nanomaterials, TiCT MXenes have garnered substantial attention for their potential in tissue regeneration. This investigation concentrates on the role of MXene nanocomposites in modulating the immune microenvironment within bone defects to facilitate bone tissue restoration. TiCT MXenes are synthetized, incorporated into beta-tricalcium phosphate ceramics (β-TCP) nanocomposites (T-MXene), and their osteoinductive and immunomodulatory effects are evaluated. The effects of T-MXene-treated T-cells on bone marrow stromal cells (BMSCs) are explored. In addition, its therapeutic potential for bone regeneration is assessed in vivo using a critical-sized mandibular bone defect model. The underlying mechanisms by which T-MXene regulates T-cell differentiation and bone regeneration are explored via whole-transcriptome RNA sequencing. The scaffolds activate N-glycosylation in T cells, which possess anti-inflammatory and antioxidant effects, thereby inducing a pro-regenerative response. T-MXene increased the proportion of IL-4 T cells among primary T cells and mandibular lymph nodes, ultimately promoting osteogenesis in BMSCs and injured mandibles. The distinctive function of MXene-based nanocomposites in osteoimmunomodulation provides a solid foundation for further exploration and application of MXenes as immune response modulators, potentially advancing their use in regenerative medicine.

During the bone tissue repair process, the highly dynamic interactions between the host and materials hinder precise, stable, and sustained immune modulation. Regulating the immune response based on potential mechanisms of macrophage phenotypic changes may represent an effective strategy for promoting bone healing. This study successfully constructs a co-dispersed pFe₃O₄-MXene nanosystem by loading positively charged magnetite (pFe₃O₄) nanoparticles onto MXene nanosheets using electrostatic self-assembly. Subsequently, this work fabricates a biomimetic porous bone scaffold (PFM) via selective laser sintering, which exhibit superior magnetic properties, mechanical performance, hydrophilicity, and biocompatibility. Further investigations demonstrate that the PFM scaffold could precisely and remotely modulate macrophage polarization toward the M2 phenotype under a static magnetic field, significantly enhancing osteogenesis and angiogenesis. Proteomic analysis reveal that the scaffold upregulates Arg2 expression, enhancing mitochondrial function and accelerating oxidative phosphorylation, thereby inducing the M2 transition. In vivo experiments validated the scaffold's immune regulatory capacity in subcutaneous and cranial defect repairs in rats, effectively promoting new bone formation. Overall, this strategy of immune modulation targeting macrophage metabolism and mitochondrial function offers novel insights for material design in tissue engineering and regenerative medicine.

A stringent analysis of the biocompatibility of MXene is a necessary condition for assessing the biological risk of MXene. Owing to high surface free energy, MXene is capable of adsorbing a large amount of blood proteins to form MXene-protein corona complexes, however, a comprehensive understanding of the relationship between MXene and cellular physiological systems remains limited. Therefore, we investigated the cellular uptake and cytotoxicity effect of MXene TiCT and PEGylation TiCT mediated by human serum protein corona in THP-1 cells. It was found that PEGylation can alter the interaction between TiCT and serum proteins, inducing a significant transformation in the fingerprint of the protein corona. Following protein corona formation, both TiCT and PEGylated TiCT predominantly accumulated at lysosomal sites within THP-1 cells. Further analysis revealed that clathrin-mediated endocytosis was the primary mechanism of TiCT internalization by THP-1 cells. There was no significant effect on cell viability. However, we found that TiCT plays a dual role as both a stimulus and scavenger of ROS within THP-1 cells, influenced by its PEGylation and the formation of a protein corona. This study provides important insights for biocompatibility evaluation and rational design of nanoproducts based on TiCT in the future.

Treating metabolic dysfunction-associated fatty liver disease (MAFLD) and reducing the occurrence of MAFLD-associated liver cancer remain challenging. Two-dimensional (2D) tantalum carbide (TaC) MXene nanozymes (MXenzymes) exhibit antioxidant and anti-inflammatory activities and have thus attracted considerable attention in the fields of oncology and engineering. However, the potential mechanism of action and bioactive properties of TaC in MAFLD remain uncertain. In our study, TaC not only inhibited lipid accumulation and disrupted lipid metabolism in hepatocytes but also reduced cell death caused by fatty acids by decreasing intracellular reactive oxygen species (ROS) levels, which significantly promoted the polarization of M1 macrophages to M2 macrophages by alleviating oxidative stress and further suppressing inflammatory factor expression. In mice fed a methionine-choline-deficient (MCD) diet, TaC reduced lipid accumulation, the infiltration of inflammatory cells, and liver cell apoptosis by modulating the cellular microenvironment through its anti-inflammatory and antioxidant properties. Therefore, TaC can be used as a multifunctional bioactive material to alleviate hepatic steatosis and inflammation in individuals with MAFLD/metabolic dysfunction-associated steatohepatitis (MASH) because of its robust antioxidant and anti-inflammatory effects.

Titanium carbide MXene flakes have promising applications in aerospace, flexible electronic devices and biomedicine owing to their superior mechanical properties and electrical conductivity and good photothermal conversion, biocompatibility and osteoinductivity. It is highly desired yet very challenging to assemble MXene flakes into macroscopic high-performance materials in a scalable manner. Here we demonstrate a scalable strategy to fabricate high-performance MXene films by roll-to-roll-assisted blade coating (RBC) integrated with sequential bridging, providing good photothermal conversion and osteogenesis efficiency under near-infrared irradiation. MXene flakes were first bridged with silk sericin by hydrogen bonding and then assembled into macroscopic films using a continuous RBC process, followed by ionic bridging to freeze their aligned structure. The resultant large-scale MXene films with strong interlayer interactions are highly aligned and densified, exhibiting high tensile strength (755 MPa), toughness (17.4 MJ m) and electromagnetic interference (EMI) shielding capacity (78,000 dB cm g), as well as good ambient stability, photothermal conversion and bone regeneration performance. The proposed strategy not only paves a feasible way for realizing the practical applications of MXene in the fields of flexible EMI shielding materials and bone tissue engineering but also provides an avenue for the high-performance and scalable assembly of other two-dimensional flakes.

Factor-free biomaterial scaffolds play an increasingly important role in promoting bone reconstruction and regeneration. However, the complicated and variable pathophysiological microenvironments of the injury sites under diabetic conditions, including the vicious cycle of oxidative stress and inflammatory response, impaired osteo/angiogenesis function and hyperactive osteoclastogenesis, as well as increased susceptibility to bacterial infection, may largely weaken the therapeutic potential of implanted scaffolds, leading to uncontrolled and poor outcomes of bone defect healing. To tackle the aforementioned challenges, a mild photothermal-assisted multifunctional therapeutic platform (denoted as GAD/MC) that integrates copper-containing two-dimensional TiCT MXene nanosheets, gelatin methacrylate, and alginate-graft-dopamine was proposed to achieve efficient and synergistic therapy for diabetic bone defects. Thereinto, copper-decorated MXene (MC) nanosheets were employed as both functional crosslinkers and nanofillers to participate in the construction of an interpenetrating polymer network structure through multiple covalent and noncovalent bonds, which conferred the hydrogel with advantageous traits like enhanced mechanical properties, injectability and moldability, strong bone tissue adhesion and self-healing ability, as well as excellent anti-swelling and near-infrared (NIR) photothermal conversion capabilities. On account of the NIR/pH dual-responsive properties, the resulting hydrogel system was capable of achieving the controlled and stimuli-responsive release of bioactive Cu, allowing on-demand delivery at the site of injury. Moreover, with the assistance of mild photothermal effects, this integrated hydrogel system demonstrated remarkable antibacterial and antioxidant properties. It effectively scavenged excessive reactive oxygen species (ROS), inhibited inflammatory responses, and promoted macrophage polarization towards the pro-healing M2 phenotype. Such characteristics were beneficial for recreating an optimized microenvironment that supported the adhesion, proliferation, migration, and differentiation of osteoblasts and endothelial cells, while concurrently inhibiting osteoclast function. In a critical-sized cranial defect model using diabetic rats, the injectable GAD/MC hydrogel system combined with on-demand mild hyperthermia further synergistically accelerated new bone formation and bone healing processes by eliminating intracellular ROS, ameliorating inflammation, orchestrating M2 macrophage polarization, promoting osteo/angiogenesis, and suppressing osteoclastogenesis. Overall, the constructed multifunctional injectable hydrogel system has emerged as a promising therapeutic candidate for addressing complex bone-related challenges by remodeling the disordered immune microenvironment and expediting the bone healing process.

Complete repair of skeletal muscles caused by severe mechanical damage and muscle-related diseases remains a challenge. 2D Ti C T (MXene) possesses special photoelectromagnetic properties and has attracted considerable attention in materials science and engineering. However, the bioactive properties and potential mechanism of MXene in tissue engineering, especially in skeletal muscle regeneration, are unclear. Herein, the antioxidation and anti-inflammation activities of MXene and its effects on myogenic differentiation and regeneration of skeletal muscle in vivo are investigated. In vitro studies have shown that MXene has excellent antioxidation and anti-inflammatory properties, and promotes myogenic differentiation and angiogenesis. MXene can remove excess reactive oxygen species in macrophage cells to alleviate oxidative stress and induce the transformation of M1 macrophages into M2 macrophages to reduce excessive inflammation, which can significantly promote the proliferation and differentiation of myoblasts, as well as the proliferation, migration, and tube formation of endothelial cells. Animal experiments with rat tibial anterior muscle defects show that MXene can promote angiogenesis, muscle fiber formation, and skeletal muscle regeneration by regulating the cell microenvironment through anti-inflammatory and antioxidant pathways. The findings suggest that MXene can be used as a multifunctional bioactive material to enhance tissue regeneration through robust antioxidation, anti-inflammation, and angiogenesis activities.

Current therapeutic approaches for volumetric muscle loss (VML) face challenges due to limited graft availability and insufficient bioactivities. To overcome these limitations, tissue-engineered scaffolds have emerged as a promising alternative. In this study, we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone) integrated with collagen and TiCT MXene nanoparticles (NPs) (PCM matrices), and explored their myogenic potential for skeletal muscle tissue regeneration. The PCM matrices demonstrated favorable physicochemical properties, including structural uniformity, alignment, microporosity, and hydrophilicity. In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts. Moreover, in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury. Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices, leading to elevated intracellular Ca levels in myoblasts through the activation of inducible nitric oxide synthase (iNOS) and serum/glucocorticoid regulated kinase 1 (SGK1), ultimately promoting myogenic differentiation via the mTOR-AKT pathway. Additionally, upregulated iNOS and increased NO contributed to myoblast proliferation and fiber fusion, thereby facilitating overall myoblast maturation. These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, TiCT MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of , scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.

Given the challenge of multidrug resistance in antibiotics, non-antibiotic-dependent antibacterial strategies show promise for anti-infective therapy. VC MXene-based nanomaterials have demonstrated strong biocompatibility and photothermal conversion efficiency (PCE) for photothermal therapy (PTT). However, the limitation of VC MXene's laser irradiation to the near-infrared region I (NIR-I) restricts tissue penetration, making it difficult to achieve complete bacterial eradication with single-effect therapeutic strategies. To address this, Pt nanoparticles (Pt NPs) are attached to VC, forming artificial nanoplatforms (Pt@VC). Pt@VC exhibits enhanced PCE (59.6%) and a longer irradiation laser (NIR-II) due to the surface plasmon resonance effect of Pt NPs and VC. Notably, Pt@VC displays dual enzyme-like activity with chemodynamic therapy (CDT) and NIR-II enhanced dual enzyme-like activity. The biocatalytic mechanism of Pt@VC is elucidated using density functional theory. In an in vivo animal model, Pt@VC effectively eliminates methicillin-resistant Staphylococcus aureus from deep-seated tissues in subcutaneous abscesses and bacterial keratitis environments, accelerating abscess resolution and promoting wound and cornea healing through the synergistic effects of PTT/CDT. Transcriptomic analysis reveals that Pt@VC targets inflammatory pathways, providing insight into its therapeutic mechanism. This study presents a promising therapeutic approach involving hyperthermia-amplified biocatalysis with Pt NPs and MXene nanocomposites.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

The compact three-dimensional (3D) structure of extracellular polymeric substances (EPS) within biofilms significantly hinders the penetration of antimicrobial agents, making biofilm eradication challenging and resulting in persistent biofilm-associated infections. To address this challenge, a solution is proposed: a probiotic bio-heterojunction (P-bioHJ) combining Lactobacillus rhamnosus with MXene (TiC) quantum dots (MQDs)/FeS heterojunction. This innovation aims to break down the saccharides in EPS, enabling effective combat against biofilm-associated infections. Initially, the P-bioHJ targets saccharides through metabolic processes, causing the collapse of EPS and allowing infiltration into bacterial colonies. Simultaneously, upon exposure to near-infrared (NIR) irradiation, the P-bioHJ produces reactive oxygen species (ROS) and thermal energy, deploying physical mechanisms to combat bacterial biofilms effectively. Following antibiofilm treatment, the P-bioHJ adjusts the oxidative environment, reduces wound inflammation by scavenging ROS, boosts antioxidant enzyme activity, and mitigates the NF-κB inflammatory pathway, thereby accelerating wound healing. In vitro and in vivo experiments confirm the exceptional antibiofilm, antioxidant/anti-inflammatory, and wound-regeneration properties of P-bioHJ. In conclusion, this study provides a promising approach for treating biofilm-related infections.

Bacterial infections, such as bacterial keratitis (BK) and subcutaneous abscess, pose significant challenges to global healthcare. Innovative and new antibacterial agents and antibacterial strategies are in demand to control infections in this era of high drug resistance. Nanotechnology is gradually emerging as an economically feasible and effective anti-infection treatment. High-entropy MXenes (HE MXenes) are used to confer desirable properties with exposed active sites to high-entropy atomic layers, whose potential application in the field of biomedicine remains to be explored. Herein, monolayer HE MXenes are fabricated by implementing transition metals with high entropy and low Gibbs free energy to fill the gap in the biocatalytic performance of non-high-entropy MXenes. HE MXenes are endowed with extremely strong oxidase mimic activity (K = 0.227 mm) and photothermal conversion efficiency (65.8%) in the second near-infrared (NIR-II) biowindow as entropy increases. Subsequently, HE MXenes realize NIR-II-enhanced intrinsic oxidase mimic activity for killing methicillin-resistant Staphylococcus aureus and rapidly removing the biofilm. Furthermore, HE MXenes can effectively treat BK and subcutaneous abscess infection induced by methicillin-resistant Staphylococcus aureus as nanotherapeutic agents with minuscule side effects. Overall, monolayer HE MXenes demonstrate promising clinical application potential in the treatment of drug-resistant bacterial infections and promote the healing of infected tissues.

Nanoparticles (NPs) have emerged as a promising solution for many biomedical applications. Although not all particles have antimicrobial or regenerative properties, certain NPs show promise in enhancing wound healing by promoting tissue regeneration, reducing inflammation, and preventing infection. Integrating various NPs can further enhance these effects. Herein, the zinc oxide (ZnO)-MXene-Ag nanocomposite was prepared, and the conjugation of its three components was confirmed through scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) mapping analysis. In vitro analysis using the agar well diffusion technique demonstrated that ZnO-MXene-Ag nanocomposite exhibited high antimicrobial efficacy, significantly inhibiting Escherichia coli, Salmonella, and Candida albicans, and showing enhanced potency when combined with tetracycline, resulting in a 2.6-fold increase against Staphylococcus and a 2.4-fold increase against Pseudomonas. The efficacy of nanocomposite-loaded carboxymethyl cellulose (CMC) gel on wound healing was investigated using varying concentrations (0, 1, 5, and 10 mg/mL). Wound healing was monitored over 21 days, with results indicating that wounds treated with 1 mg/mL ZnO-MXene-Ag gel exhibited superior healing compared to the control group (0 mg/mL), with significant improvements noted from Day 3 onward. Conversely, higher concentrations (10 mg/mL) resulted in reduced healing efficiency, particularly notable on Day 15. In conclusion, the ZnO-MXene-Ag nanocomposite-loaded CMC gel is a promising agent for enhanced wound healing and antimicrobial applications. These findings highlight the importance of optimizing NP concentration to maximize therapeutic benefits while minimizing potential cytotoxicity.

Reactive oxygen species (ROS) are generated and consumed in living organism for normal metabolism. Paradoxically, the overproduction and/or mismanagement of ROS have been involved in pathogenesis and progression of various human diseases. Here, we reported a two-dimensional (2D) vanadium carbide (VC) MXene nanoenzyme (MXenzyme) that can mimic up to six naturally-occurring enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione peroxidase (GPx), thiol peroxidase (TPx) and haloperoxidase (HPO). Based on these enzyme-mimicking properties, the constructed 2D VC MXenzyme not only possesses high biocompatibility but also exhibits robust in vitro cytoprotection against oxidative stress. Importantly, 2D VC MXenzyme rebuilds the redox homeostasis without perturbing the endogenous antioxidant status and relieves ROS-induced damage with benign in vivo therapeutic effects, as demonstrated in both inflammation and neurodegeneration animal models. These findings open an avenue to enable the use of MXenzyme as a remedial nanoplatform to treat ROS-mediated inflammatory and neurodegenerative diseases.

Diabetic wounds pose a clinical challenge due to persistent inflammation, severe bacterial infections, inadequate vascularization, and pronounced oxidative stress. Current therapeutic modalities fail to provide satisfactory outcomes in managing these conditions, resulting in considerable patient distress. Two-dimensional nanomaterials (2DNMs), characterized by their unique nanosheet structures, expansive surface areas, and remarkable physicochemical properties, have garnered considerable attention for their potential in therapeutic applications. Emerging 2DNMs can be loaded with various pharmacological agents, including small molecules, metal ions, and liposomes. Moreover, they can be integrated with various biomaterials such as hydrogels, microneedles, and microspheres, thus demonstrating unprecedented advantages in expediting the healing process of diabetic wounds. Moreover, 2DNMs exhibit exceptional performance characteristics, including high biocompatibility, effective antimicrobial properties, optimal phototherapeutic effects, and enhanced electrostimulation capabilities. These properties enable them to modulate the wound microenvironment, leading to widespread application in tissue repair with remarkable outcomes. This review delineates several emerging 2DNMs, such as graphene and its derivatives, black phosphorus, MXenes, and transition metal dichalcogenides, in the context of diabetic wound repair. Furthermore, it elucidates the translational challenges and future perspectives of 2DNMs in wound healing treatments. Overall, 2DNMs present a highly promising strategy for ameliorating diabetic wounds, thus providing novel avenues for diagnostic and therapeutic strategies in diabetic wound management.

Currently, exosomes showed appropriate potential in the repair of skin injury. However, the functions of the exosomes could be compromised rapidly due to their short half-life and high clearance rate in vivo. In addition, the controlled release of effective concentrations of exosomes could increase the utilization efficiency of exosomes in wound healing. Accordingly, the design of an effective system for the controlled delivery of exosomes during the wound treatment period was necessary. In this contribution, we designed a novel exosome-based multifunctional nanocomposite platform with photothermal-controlled release performance for the repair of skin injury. Based on the agarose hydrogel, two-dimensional TiC (TiC MXene) and human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes, the as-prepared platform (i.e., hucMSC-derived exosome/TiC MXene hydrogel) was synthesized for the first time. Apart from possessing injectability, the hucMSC-derived exosome/TiC MXene hydrogel utilized the excellent photothermal effect of TiC MXene and proper phase transition performance of agarose hydrogel to provide a photothermal-controlled release system for the hucMSC-derived exosomes, which was beneficial for the personalized on-demand drug delivery. Importantly, the hucMSC-derived exosomes maintained their inherent structure and activity after being released from the TiC MXene hydrogel. Additionally, the as-prepared hydrogel with multifunctional performance also presented remarkable biocompatibility and photothermal-antibacterial property, and could efficiently accelerate wound healing by promoting cell proliferation, angiogenesis, collagen deposition, and reducing the level of inflammation at the wound site. The results suggested that the exosome-based multifunctional nanocomposite platform with great potential for wound healing would make significant advances in the revolution of traditional treatment methods in skin injury.

BACKGROUND:Most bone defects caused by bone disease or trauma are accompanied by infection, and there is a high risk of infection spread and defect expansion. Traditional clinical treatment plans often fail due to issues like antibiotic resistance and non-union of bones. Therefore, the treatment of infected bone defects requires a strategy that simultaneously achieves high antibacterial efficiency and promotes bone regeneration. RESULTS:In this study, an ultrasound responsive vanadium tetrasulfide-loaded MXene (VSM) Schottky junction is constructed for rapid methicillin-resistant staphylococcus aureus (MRSA) clearance and bone regeneration. Due to the peroxidase (POD)-like activity of VS and the abundant Schottky junctions, VSM has high electron-hole separation efficiency and a decreased band gap, exhibiting a strong chemodynamic and sonodynamic antibacterial efficiency of 94.03%. Under the stimulation of medical dose ultrasound, the steady release of vanadium element promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The in vivo application of VSM in infected tibial plateau bone defects of rats also has a great therapeutic effect, eliminating MRSA infection, then inhibiting inflammation and improving bone regeneration. CONCLUSION:The present work successfully develops an ultrasound responsive VS-based versatile sonosensitizer for robust effective antibacterial and osteogenic therapy of infected bone defects.

In the field of bone tissue engineering, the practical application of growth factors is limited by various factors such as systemic toxicity, instability, and the potential to induce inflammation. To circumvent these limitations, the use of physical signals, such as thermal stimulation, to regulate stem cells has been proposed as a promising alternative. The present study aims to investigate the potential of the two-dimensional nanomaterial TiC MXene, which exhibits unique photothermal properties, to induce osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) photothermal conversion. Surface modification of TiC MXene nanosheets with PVP (TiC-PVP) was employed to enhance their colloidal stability in physiological solutions. Characterization and cellular experiments showed that TiC-PVP nanosheets have favorable photothermal properties and biocompatibility. Our study demonstrated that the induction of photothermal stimulation by co-culturing TiC-PVP nanosheets with BMSCs and subsequent irradiation with 808 nm NIR significantly promoted cell proliferation, adhesion and osteogenic differentiation of BMSCs. In conclusion, the results of this study suggest that TiC-PVP is a promising material for bone tissue engineering applications as it can modulate the cellular functions of BMSCs through photothermal conversion.

Wound healing is a complex physiological process that involves coordinated phases such as inflammation and neovascularization. Attempts to promote the healing process tend to construct an effective delivery system based on different drugs and materials. In this paper, we propose novel MXene-integrated microneedle patches with adenosine encapsulation for wound healing. Owing to the dynamic covalent bonding capacity of boronate molecules with adenosine, 3-(acrylamido)phenylboronic acid- (PBA-) integrated polyethylene glycol diacrylate (PEGDA) hydrogel is utilized as the host material of microneedle patches. Benefitting from photothermal conversion capacity of MXene, the release of loaded adenosine could be accelerated under NIR irradiation for maintaining the activation signal around injury site. In vitro cell experiments proved the effect of MXene-integrated microneedle patches with adenosine encapsulation in enhancing angiogenesis. When applied for treating animal models, it is demonstrated that the microneedle patches efficiently promote angiogenesis, which is conductive to wound healing. These features make the proposed microneedle patch potential for finding applications in wound healing and other biomedical fields.

Contact lenses (CLs) are prone to adhesion and invasion by pollutants and pathogenic bacteria, leading to infection and inflammatory diseases. However, the functionalization of CL (biological functions such as anti-fouling, antibacterial, and anti-inflammatory) and maintaining its transparency still face great challenges. In this work, as a member of the MXenes family, vanadium carbide (VC) is modified onto CL via a water transfer printing method after the formation of a tightly arranged uniform film at the water surface under the action of the Marangoni effect. The coating interface is stable owing to the electrostatic forces. The VC-modified CL (VC@CL) maintains optical clarity while providing good biocompatibility, strong antioxidant properties, and anti-inflammatory activities. In vitro antibacterial experiments indicate that VC@CL shows excellent performance in bacterial anti-adhesion, sterilization, and anti-biofilm formation. Last, VC@CL displays notable advantages of bacteria elimination and inflammation removal in infectious keratitis treatment.

The regeneration of skin tissue is often impeded by bacterial infection seriously. At the same time, reactive oxygen species (ROS) are often overexpressed in infected skin wounds, causing persistent inflammation that further hinders the skin repair process. All of these make the treatment of infected wounds is still a great challenge in clinic. In this study, we fabricate Cu(II)@MXene photothermal complex based on electrostatic self-assembly between Cu and MXene, which are then introduced into a hyaluronic acid (HA) hydrogel to form an antibacterial dressing. The rapid adhesion, self-healing, and injectability of the dressing allows the hydrogel to be easily applied to different wound shapes and to provide long-term wound protection. More importantly, this easily prepared Cu(II)@MXene complex can act as a photothermal antibacterial barrier, ROS scavenger and angiogenesis promoter simultaneously to accelerate the healing rate of infected wounds. Our experiments strongly proved that the inflammatory condition, collagen deposition, vessel formation, and the final wound closure area were all improved by the application of Cu(II)@MXene photothermal hydrogel dressing.

Compared with the photoacoustic imaging (PAI) in the first near-infrared window (NIR-I, 700-1000 nm), the PAI in the second near-infrared window (NIR-II, 1000-1700 nm) has the advantages of less background noise, deeper tissue penetration, and larger maximum permissible exposure, which has been become a research hotspot. In this review, the recent advances in nanomaterials for NIR-II PAI are summarized, including the advantages of NIR-II PAI and the applications of nanomaterials-based NIR-II PAI in biomedical field. The nanomaterials-based PA contrast agents are classified into three categories, including organic (such as assembled small molecules, conjugated polymers, semiconducting polymers, and phthalocyanines), inorganic (such as metal sulfides, noble metals, carbon nanomaterials, quantum dots, 2D transition metal carbides and nitrides [MXenes], and semimetals), or organic/inorganic hybrid nanomaterials, which are mainly used for imaging and diagnosis of tumor tissues, brain vasculature, inflammation, and other tissues, as well as the monitoring of catalytic reaction processes in vivo. Moreover, the opportunities and challenges of NIR-II PAI are also expounded.

Recently, we developed highly fluorescent Ti C and Nb C Mxene quantum dots (QDs) for labeling of in vitro models. However, the mechanism of the toxicity of the prepared QDs was not explored before. In this study, we addressed the possible mechanism associated with cytotoxicity of the QDs to human umbilical vein endothelial cells (HUVECs). Exposure to up to 100 μg/ml Ti C but not Nb C QDs for 24 h significantly induced cytotoxicity. The exposure also increased intracellular Ti and Nb elements, indicating the internalization of both types of QDs. None of the QDs promoted interleukin 6 (IL-6) and IL-8 releases. Rather, Ti C QDs significantly reduced IL-6 and IL-8 release, indicating that the toxicity of Ti C QDs was not due to elevated inflammatory responses. Exposure to Ti C but not Nb C QDs resulted in increased LC3B-II/I ratio and beclin-1 proteins, biomarkers of autophagy, as well as the accumulation of autophagic substance p62. Ti C QDs also more effectively promoted pro-caspase 3 but not pro-caspase 8 compared with Nb C QDs. Furthermore, pre-treatment with autophagic modulators altered the cytotoxicity of Ti C QDs, which further confirmed the role of autophagic dysfunction in Ti C QD-induced toxicity to HUVECs. In conclusion, the results from this study suggested that high levels of Ti C QDs could induce cytotoxicity to HUVECs by inducing the dysfunction of autophagy. Nb C QDs appeared to be more biocompatible to HUVECs compared with Ti C QDs at the same mass concentrations, which suggested a role of composition of Mxene QDs to determine their toxicity to human endothelial cells.

The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to develop nanoformulations capable of adaptively releasing antimicrobial factors and demonstrating multimodal synergistic antimicrobial activity. Herein, an NIR-activated multifunctional synergistic antimicrobial nanospray MXene/ZIF-90@ICG was prepared by incorporating ZIF-90@ICG nanoparticles onto MXene-NH nanosheets. MXene/ZIF-90@ICG can on-demand release the antimicrobial factors MXenes, ICG, and Zn in response to variations in pH and ATP levels within the bacterial infection microenvironment. Under NIR radiation, the combination of MXenes, Zn, and ICG generated a significant amount of ROS and elevated heat, thereby enhancing the antimicrobial efficacy of PDT and PTT. Meanwhile, NIR excitation could accelerate the further release of ICG and Zn, realizing the multimodal synergistic antibacterial effect of PDT/PTT/Zn. Notably, introducing MXenes improved the dispersion of the synthesized antimicrobial nanoparticles in aqueous solution, rendering MXene/ZIF-90@ICG a candidate for application as a nanospray. Importantly, MXene/ZIF-90@ICG demonstrated antimicrobial activity and accelerated wound healing in the constructed subcutaneous infection model with NIR activation, maintaining a favorable biosafety level. Therefore, MXene/ZIF-90@ICG holds promise as an innovative nanospray for adaptive multimodal synergistic and efficient antibacterial applications with NIR activation.

Pathogenic microorganisms' infections have always been a difficult clinical challenge and lead to serious health problems. Thus, a new strategy is urgently needed. In this study, a simple preparation method for Ti C MXene colloidal solution is proposed. In vitro, Staphylococcus aureus is treated with 250 µg mL of Ti C colloidal solution under 5 min of 808 nm near-infrared (NIR) laser irradiation twice. Staphylococcus aureus is eliminated by the "nanothermal blade" effect from Ti C combined with NIR; the antibacterial rate is 99%, which is higher than the antibacterial rate of pure Ti C alone 78%. The antibacterial mechanism underlying this treatment may be that the thermal Ti C nanosheets first transfer heat to the cell membrane, disrupting the membrane structure, disturbing the metabolism and causing leakage of bacterial protein and deoxyribonucleic acid, consequently leading to bacterial death. In vivo results indicate that Ti C colloidal solution under NIR can effectively kill Staphylococcus aureus and prevent inflammation. Moreover, 250 µg mL Ti C colloidal solution is nontoxic to mouse organs during the therapeutic process. Therefore, Ti C colloidal solution can be an ideal candidate for subcutaneous infection application. The antibacterial mechanism proposed in this study aids the investigation of other MXenes as antibacterial agents.

To date, implant-associated infection is still a significant clinical challenge, which cannot be effectively eliminated by single therapies due to the formation of microbial biofilms. Herein, a pH-responsive nanoplatform was constructed the growth of zinc sulfide (ZnS) nanoparticles on the surface of TiC MXene nanosheets, which was subsequently introduced in poly(L-lactic acid) (PLLA) to prepare a composite bone scaffold selective laser sintering technology. In the acidic biofilm microenvironment, the degradation of ZnS released hydrogen sulfide (HS) gas to eliminate the biofilm extracellular DNA (eDNA), thus destroying the compactness of the biofilm. Then, the bacterial biofilm became sensitive to hyperthermia, which could be further destroyed under near-infrared light irradiation due to the excellent photothermal property of MXene, finally achieving gas/photothermal synergistic antibiofilm and efficient sterilization. The results showed that the synergistic gas/photothermal therapy for the composite scaffold not only evidently inhibited the formation of biofilms, but also effectively eradicated the eDNA of the already-formed biofilms and killed 90.4% of and 84.2% of under near infrared light irradiation compared with single gas or photothermal therapy. In addition, the composite scaffold promoted the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Thus, the designed scaffold with excellent biofilm elimination and osteogenesis ability has great potential as an alternative treatment for implant-associated bone infections.

BACKGROUND:Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers. RESULTS:The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds. CONCLUSIONS:The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection.

Chronic bacterial-infected wound healing/skin regeneration remains a challenge due to drug resistance and the poor quality of wound repair. The ideal strategy is combating bacterial infection, while facilitating satisfactory wound healing. However, the reported strategy hardly achieves these two goals simultaneously without the help of antibiotics or bioactive molecules. In this work, a two-dimensional (2D) TiCT MXene with excellent conductivity, biocompatibility, and antibacterial ability was applied in developing multifunctional scaffolds (HPEM) for methicillin-resistant (MRSA)-infected wound healing. HPEM scaffolds were fabricated by the reaction between the poly(glycerol-ethylenimine), TiCT MXene@polydopamine (MXene@PDA) nanosheets, and oxidized hyaluronic acid (HCHO). HPEM scaffolds presented multifunctional properties containing self-healing behavior, electrical conductivity, tissue-adhesive feature, antibacterial activity especially for MRSA resistant to many commonly used antibiotics (antibacterial efficiency was 99.03%), and rapid hemostatic capability. HPEM scaffolds enhanced the proliferation of normal skin cells with negligible toxicity. Additionally, HPEM scaffolds obviously accelerated the MRSA-infected wound healing (wound closure ratio was 96.31%) by efficient anti-inflammation effects, promoting cell proliferation, and the angiogenic process, stimulating granulation tissue formation, collagen deposition, vascular endothelial differentiation, and angiogenesis. This study indicates the important role of multifunctional 2D MXene@PDA nanosheets in infected wound healing. HPEM scaffolds with multifunctional properties provide a potential strategy for MRSA-infected wound healing/skin regeneration.

Localized chemotherapy is emerging as a potential strategy for cancer treatment due to its low systemic toxicity. However, the immune evasion of tumor cells and the lack of an intelligent design of the delivery system limit its clinical application. Herein, photothermal responsive microcarriers are designed by microfluidic electrospray for colorectal tumor treatment. The microcarriers loaded with Cangrelor, 5-FU and MXene (G-M@F/C+NIR) show sustained delivery of antiplatelet drug Cangrelor, thus inhibiting the activity of platelets, interactions of platelet-tumor cell, as well as the tumor cells invasion and epithelial-mesenchymal transition (EMT). In addition, the sustained delivery of chemotherapeutics 5-FU and the photothermal effect provided by MXene enable the microcarriers to inhibit tumor cells proliferation and migration. In vivo studies validate that the G-M@F/C+NIR microcarriers significantly inhibites tumor growth, decreased the expression of Ki-67 in tumor cells and vascular endothelial growth factor (VEGF) in the tumor microenvironment, while increased the expression of E-cadherin. It is believe that by means of the proposed photothermal responsive microcarriers, the synergistic strategy of platelet inhibition, chemotherapy, and photothermal therapy can find practical applications in cancer treatment.

The adhesion of bacteria to the surface leads to formation of biofilms causing numerous infection problems in implanting medical devices or interventional therapy. Traditional treatment for such problems is generally to administrate patients with antibiotics or antifungal agent. Alternatively, devices are taken out of the body to mechanically destroy the biofilm and re-used by surgery. In this study, a straightforward method was developed to remove biofilms using a MXene-based photothermal hydrogel. The hydrogel consists of dynamic crosslinking network formed by Schiff-base reaction between aldehyde-containing xyloglucan (OXG) and amine-containing MXene (NH-MXene), which showed efficient killing of both gram-positive () and gram-negative () bacteria upon near-infrared (NIR) laser irradiation. The NH-MXene/OXG nanocomposite hydrogel showed a high photothermal antibacterial efficiency and stable photothermal conversion, demonstrated by efficient removal of biofilms .

The high mortality and enormous economic burden of bacterially infected wounds remains a huge challenge for human health. The development of ideal wound dressings with desirable antibacterial and good wound healing properties still remains a major problem affecting the regeneration of bacterially infected wound tissue. Herein, we present novel alginate-based hydrogel microspheres containing lysozyme and MXene (i-Lyso@Alg), in which the positively charged lysozyme is immobilized on the negatively charged MXene by electrostatic interaction. Due to the presence of MXene, i-Lyso@Alg exhibits good thermal effect, drug release behavior and strong antibacterial activity under near-infrared (NIR) irradiation. The synthesized i-Lyso@Alg can realize not only improvement of lysozyme stability but also photothermal responsive up-regulation for biocatalysis of lysozyme. The excellent antibacterial activities of i-Lyso@Alg were attributed to the photothermally enhanced lysozyme activity, assisted by bacterial death caused by local thermal effect of photothermally activated MXene and the physical damage due to the MXene. In addition, in the infected skin wounds of rats, i-Lyso@Alg + NIR significantly accelerates the wound healing process by inhibiting the expression of inflammatory factors and bacterial (Staphylococcus aureus) infection, and inducing the expression of pro-angiogenic factors and tissue remodeling. Overall, the results of this study introduce a pioneering approach by integrating the unique photothermal properties of MXene with the enzymatic action of lysozyme within an alginate-based hydrogel microsphere. This synergistic system not only advances the frontier of antibacterial wound dressings but also represents a significant step towards effective management of infected wounds, which possesses great potential in clinical treatment of infected wounds.

Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti C MXene/MoS (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the "ROS hurricane" from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO-induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds.

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size TiCT MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size TiCT MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /VC MXene bio-heterojunctions (2D-bioHJs) is devised. Under ultrasonication, 2D-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.

Incurable bacterial infections, impenetrable microbial biofilm, and irreversible antibiotic resistance are among the most dangerous threats for humans. With few effective strategies available in antimicrobial and antibiofilm development, innovative methodologies inspired by the advances in other fields such as nanomedicine are becoming more and more attractive to realize innovative antibacterial agents. Herein, a 2D niobium carbide (NbC) MXene titanium plate (NbC@TP)-based clinical implant with practical multimodal anti-infection functions was developed. Such emerging modes are capable of destroying biofilms for direct bacteria elimination through down-regulating bacterial energy metabolism pathways, suppressing biofilm formation, and enhancing as-formed biofilm detachment an activating accessory gene regulator. Another intriguing feature of this nanomedicine is the sensitization ability toward bacteria photothermal transduction, which reduces the temperature necessary for bacteria eradication and mitigates possible normal tissue damage. Moreover, the NbC@TP medical implant is able to alleviate proinflammatory responses by scavenging excessive reactive oxygen species in infectious microenvironments, benefiting angiogenesis and tissue remodeling.

The bone defects caused by trauma are inevitably accompanied by soft tissue damage. The development of multifunctional bioactive biomaterials with integrated bone and soft tissue regeneration is necessary and needed urgently in orthopedics. In this work, we found that the photoactivated MXene (TiCT) nanosheet showed positive effects on promoting both bone and soft tissue regeneration. We further investigated the detailed effect and potential mechanism of photoactivated MXene on tissue regeneration. Photoactivated MXene shows a good thermal effect and robust antibacterial activity to inhibit the expression of inflammation factors and methicillin-resistant (MRSA) infection and induces the expression of pro-angiogenic factors and soft tissue wound repair. Photoactivated MXene can also regulate the osteogenic differentiation of adipose-derived stem cells (ADSCs) through the ERK signaling pathway by activating the heat shock protein 70 (HSP70) and enhancing the repair of bone tissue. This work sheds light on the development of bioactive MXene with photothermal activation as an efficient strategy for bone and soft tissue regeneration simultaneously.

MXenes, a class of two-dimensional materials, exhibit considerable potential in wound healing and dressing applications due to their distinctive attributes, including biocompatibility, expansive specific surface area, hydrophilicity, excellent electrical conductivity, unique mechanical properties, facile surface functionalization, and tunable band gaps. These materials serve as a foundation for the development of advanced wound healing materials, offering multifunctional nanoplatforms with theranostic capabilities. Key advantages of MXene-based materials in wound healing and dressings encompass potent antibacterial properties, hemostatic potential, pro-proliferative attributes, photothermal effects, and facilitation of cell growth. So far, different types of MXene-based materials have been introduced with improved features for wound healing and dressing applications. This review covers the recent advancements in MXene-based wound healing and dressings, with a focus on their contributions to tissue regeneration, infection control, anti-inflammation, photothermal effects, and targeted therapeutic delivery. We also discussed the constraints and prospects for the future application of these nanocomposites in the context of wound healing/dressings.

Traditional dendritic cell (DC)-mediated immunotherapy is usually suppressed by weak immunogenicity in tumors and generally leads to unsatisfactory outcomes. Synergistic exogenous/endogenous immunogenic activation can provide an alternative strategy for evoking a robust immune response by promoting DC activation. Herein, Ti C MXene-based nanoplatforms (termed MXP) are prepared with high-efficiency near-infrared photothermal conversion and immunocompetent loading capacity to form endogenous/exogenous nanovaccines. Specifically, the immunogenic cell death of tumor cells induced by the photothermal effects of the MXP can generate endogenous danger signals and antigens release to boost vaccination for DC maturation and antigen cross-presentation. In addition, MXP can deliver model antigen ovalbumin (OVA) and agonists (CpG-ODN) as an exogenous nanovaccine (MXP@OC), which further enhances DC activation. Importantly, the synergistic strategy of photothermal therapy and DC-mediated immunotherapy by MXP significantly eradicates tumors and enhances adaptive immunity. Hence, the present work provides a two-pronged strategy for improving immunogenicity and killing tumor cells to achieve a favorable outcome in tumor patients.

Improper management of diabetic wound effusion and disruption of the endogenous electric field can lead to passive healing of damaged tissue, affecting the process of tissue cascade repair. This study developed an extracellular matrix sponge scaffold (KP@Mxene) by incorporating Mxene into an acellular dermal stroma-hydroxypropyl chitosan interpenetrating network structure. This scaffold is designed to couple with the endogenous electric field and promote precise tissue remodelling in diabetic wounds. The fibrous structure of the sponge closely resembles that of a natural extracellular matrix, providing a conducive microenvironment for cells to adhere grow, and exchange oxygen. Additionally, the inclusion of Mxene enhances antibacterial activity(98.89%) and electrical conductivity within the scaffold. Simultaneously, KP@Mxene exhibits excellent water absorption (39 times) and porosity (91%). It actively interacts with the endogenous electric field to guide cell migration and growth on the wound surface upon absorbing wound exudate. In in vivo experiments, the KP@Mxene sponge reduced the inflammatory response in diabetic wounds, increased collagen deposition and arrangement, promoted microvascular regeneration, Facilitate expedited re-epithelialization of wounds, minimize scar formation, and accelerate the healing process of diabetic wounds by 7 days. Therefore, this extracellular matrix sponge scaffold, combined with an endogenous electric field, presents an appealing approach for the comprehensive repair of diabetic wounds.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Long-range surface plasmon resonance (LRSPR) has demonstrated excellent performance in sensing and detection, due to its higher accuracy and sensitivity compared with conventional surface plasmon resonance (cSPR). In this work, we establish an LRSPR biosensor which employs PDA/TiC-MXene/PDA-gold film as a sensing substrate and gold nanoparticles (AuNPs) as enhancers. TiC-MXene is an emerging two-dimensional (2D) layered material which is used extensively in immunoassay and biosensing. The sensing substrate comprises two polydopamine (PDA) films between which is sandwiched a TiC-MXene film based on a gold film, which provides a large surface area and abundant binding sites to rabbit anti-human IgG (Ab). Sandwich amplification is adopted to enhance the sensitivity of the LRSPR biosensor, and AuNPs/staphylococcal protein A (SPA)/mouse anti-human IgG (Ab) composites are introduced into the flow cell as enhancers after the immune binding of human IgG to Ab. The antigen (human IgG) detection range is 0.075 μg mL to 40 μg mL, and the limit of detection is almost 20 times lower than that for cSPR biosensors. This novel LRSPR biosensor demonstrates excellent performance in immune sensing over a broad detection range and a low limit of detection. Subsequent modification of the LRSPR sensing platform could be made for extensive application in various biological detection fields.

A dual-readout immunosensor coupled with electrochemical impedance and temperature signal was successfully proposed to detect autoimmune hepatitis markers (ASGPR). NbC MXene with excellent conductivity, abundant surface functional groups, and extraordinary photothermal conversion efficiency, was designed to be a multifunctional biological probe, whose specific binding with antigen enhanced steric hindrance to generate electrochemical impedance signal, and at the same time, it had a strong optical response in the near-infrared band to achieve temperature output. In addition, poly(N-isopropyl acrylamide) (PNIPAM) was a temperature-sensitive polymer, which was adopted as the sensing matrix. When the multifunctional probe was specifically bound to the antigen, under 808-nm laser irradiation, the captured NbC MXene achieved photothermal conversion to increase the electrode surface temperature, and the conformation of PNIPAM changed from a free spiral to a spherical shape, further realizing double amplification of the EIS signal. Under the optimized experimental conditions, the impedance values and the temperature changes increased proportionally with the increase of the ASGPR concentration from 10 to 1 ng/mL, and the detection limit of the immunosensor was 3.3 × 10 ng/mL. The established dual-readout immunosensor exhibited good selectivity and acceptable stability and provided an effective detection method for autoimmune hepatitis marker detection.

The effective control of microbial and metabolically derived biological toxins which negatively impact physical health remains a key challenge for the 21st century. 2-Dimensional graphene and MXene nanomaterials are relatively new additions to the field of biomedical materials with superior external surface areas suited to adsorptive remediation of biological toxins. However, relatively little is known about their physiological interactions with biological systems and, to date, no comparative biological studies have been done. This study compares titanium carbide MXene (Ti3C2Tx) in multilayered and delaminated forms with graphene variants to assess the impact of variable physical properties on cellular inflammatory response to endotoxin stimulus. No significant impact on cell metabolism or induction of inflammatory pathways leading to cell death was observed. No significant increase in markers of blood cell activation and haemolysis occurred. Whilst graphene nanoplatelets (GNP), graphene oxide (GO) and Ti3C2Tx showed insignificant antibacterial activity towards Escherichia coli, silver nanoparticle-modified GO (GO-Ag) induced bacterial cell death and at a lower dose than silver nanoparticles. All nanomaterials significantly reduced bacterial endotoxin induced THP-1 monocyte IL-8, IL-6 and TNF-α cytokine production by >99%, >99% and >80% respectively, compared to control groups. This study suggests the utility of these nanomaterials as adsorbents in blood contacting medical device applications for removal of inflammatory cytokines linked to poor outcome in patients with life-threatening infection.

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D TiCT MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.

Precise delivery of therapeutic protein drugs that specifically modulate desired cellular responses is critical in clinical practice. However, the spatiotemporal regulation of protein drugs release to manipulate the target cell population in vivo remains a huge challenge. Herein, we have rationally developed an injectable and Near-infrared (NIR) light-responsive MXene-hydrogel composed of TiC, agarose, and protein that enables flexibly and precisely control the release profile of protein drugs to modulate cellular behaviors with high spatiotemporal precision remotely. As a proof-of-concept study, we preloaded hepatic growth factor (HGF) into the MXene@hydrogel (MXene@agarose/HGF) to activate the c-Met-mediated signaling by NIR light. We demonstrated NIR light-instructed cell diffusion, migration, and proliferation at the user-defined localization, further promoting angiogenesis and wound healing in vivo. Our approach's versatility was validated by preloading tumor necrotic factor-α (TNF-α) into the composite hydrogel (MXene@agarose/TNF-α) to promote the pro-apoptotic signaling pathway, achieving the NIR light-induced programmed cell deaths (PCD) of tumor spheroids. Taking advantage of the deep-tissue penetrative NIR light, we could eradicate the deep-seated tumors in a xenograft model exogenously. Therefore, the proposed MXene-hydrogel provides the impetus for developing therapeutic synthetic materials for light-controlled drug release under thick tissue, which will find promising applications in regenerative medicine and tumor therapy. STATEMENT OF SIGNIFICANCE: Current stimuli-responsive hydrogels for therapeutic proteins delivery mainly depend on self-degradation, passive diffusion, or the responsiveness to cues relevant to diseases. However, it remains challenging to spatiotemporally deliver protein-based drugs to manipulate the target cell population in vivo in an "on-demand" manner. Therefore, we have rationally constructed an injectable and Near-infrared (NIR) light-responsive composite hydrogel by embedding TiC MXene and protein drugs within an agarose hydrogel to enable the remote control of protein drugs delivery with high spatiotemporal precision. The NIR light-controlled release of the growth factor or cytokine has been carried out to regulate receptor-mediated cellular behaviors under deep tissue for skin wound healing or cancer therapy. This system will provide the potential for precision medicine through the development of intelligent drug delivery systems.

This study proposes the fabrication of a highly sensitive electrochemical immunosensor for label-free detection of EpCAM antigen. MXenes, novel 2D materials have become popular owing to their unique electrochemical properties. Unlike conventional immunosensors, which are unable to detect the carcinoma at primary stage and also time consuming, the use of highly conducting MXene provides a label-free and highly sensitive immunosensor. Herein, we develop a unique immunosensor, which is based on the in-situ growth of 2D-TiO onto the novel 2D-TiCT sheets by hydrothermal treatment. The 2D/2D TiO/TiCT hybrid provides a platform having a large effective surface area, and more number of electrochemically active sites to enhance the electron transfer rate through the redox probe. The designed sensing platform, BSA/anti-EpCAM/TiO/TiCT@ITO shows a broad linear range (1 ag/mL to 10 ng/mL) with high sensitivity (6.661 µA ag mL cm), and low detection limit (0.7 ag/mL) for EpCAM antigen detection under optimized conditions. The proposed immunosensor possesses good reproducibility, long-term stability, and outstanding selectivity and specificity. Moreover, the clinical applicability of the novel immunosensor is tested in spiked human serum showing good recovery.

MXene nanomaterials have sparked significant interest among interdisciplinary researchers to tackle today's medical challenges. In particular, colloidal MXene quantum dots (MQDs) offer the high specific surface area and compositional flexibility of MXene while providing improvements to aqueous stability and material-cell interactions. The current study for the first time reports the development and application of immunoengineered tantalum-carbide (TaCT ) MQDs for in vivo treatment of transplant vasculopathy. This report comes at a critical juncture in the field as poor long-term safety of other MXene compositions challenge the eventual clinical translatability of these materials. Using rational design and synthesis strategies, the TaCT MQDs leverage the intrinsic anti-inflammatory and antiapoptotic properties of tantalum to provide a novel nanoplatform for biomedical engineering. In particular, these MQDs are synthesized with high efficiency and purity using a facile hydrofluoric acid-free protocol and are enriched with different bioactive functional groups and stable surface TaO and TaO. Furthermore, MQDs are spontaneously uptaken into antigen-presenting endothelial cells and alter surface receptor expression to reduce their activation of allogeneic T-lymphocytes. Finally, when applied in vivo, TaCT MQDs ameliorate the cellular and structural changes of early allograft vasculopathy. These findings highlight the robust potential of tailored TaCT MQDs for future applications in medicine.

MXenes are an emerging class of nanomaterials with significant potential for applications in nanomedicine. Amongst MXene technologies, titanium carbide (TiCT) nanomaterials are the most mature and have received significant attention to tackle longstanding clinical challenges due to its tailored physical and material properties. Cardiac allograft vasculopathy is an aggressive form of atherosclerosis and a major cause of mortality among patients with heart transplants. Blood vessel endothelial cells (ECs) stimulate alloreactive T-lymphocytes to result in sustained inflammation. Herein, we report the first application of TiCT MXene nanosheets for prevention of allograft vasculopathy. MXene nanosheets interacted with human ECs and downregulated the expression of genes involved in alloantigen presentation, and consequently reduced the activation of allogeneic lymphocytes. RNA-Seq analysis of lymphocytes showed that treatment with MXene downregulated genes responsible for transplant-induced T-cell activation, cell-mediated rejection, and development of allograft vasculopathy. In an rat model of allograft vasculopathy, treatment with MXene reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted aortic allografts. These findings highlight the potential of TiCT MXene in treatment of allograft vasculopathy and inflammatory diseases.

Periprosthetic osteolysis induced by the ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles is a major complication associated with the sustained service of artificial joint prostheses and often necessitates revision surgery. Therefore, a smart implant with direct prevention and repair abilities is urgently developed to avoid painful revision surgery. Herein, we fabricate a phosphatidylserine- and polyethylenimine-engineered niobium carbide (NbC) MXenzyme-coated micro/nanostructured titanium implant (PPN@MNTi) that inhibits UHMWPE particle-induced periprosthetic osteolysis. The specific mechanism by which PPN@MNTi operates involves the bioresponsive release of nanosheets from the MNTi substrate within an osteolysis microenvironment, initiated by the cleavage of a thioketal-dopamine molecule sensitive to reactive oxygen species (ROS). Subsequently, functionalized NbC MXenzyme could target macrophages and escape from lysosomes, effectively scavenging intracellular ROS through its antioxidant nanozyme-mimicking activities. This further achieves the suppression of osteoclastogenesis by inhibiting NF-κB/MAPK and autophagy signaling pathways. Simultaneously, based on the synergistic effect of MXenzyme-integrated coatings and micro/nanostructured topography, the designed implant promotes the osteogenic differentiation of bone mesenchymal stem cells to regulate bone homeostasis, further achieving advanced osseointegration and alleviable periprosthetic osteolysis . This study provides a precise prevention and repair strategy of periprosthetic osteolysis, offering a paradigm for the development of smart orthopedic implants.

Oxidative stress, resulting from excessive reactive oxygen species (ROS), plays an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, developing novel strategies to target the disease location and treat inflammation is urgently needed. Herein, we designed and developed a novel and effective antioxidant orally-administered nanoplatform based on simulated gastric fluid (SGF)-stabilized titanium carbide MXene nanosheets (TiC NSs) with excellent biosafety and multiple ROS-scavenging abilities for IBD therapy. This broad-spectrum and efficient ROS scavenging performance was mainly relied on the strong reducibility of Ti-C bound. Intracellular ROS levels confirmed that TiC NSs could efficiently eliminate excess ROS against oxidative stress-induced cell damage. Following oral administration, negatively-charged TiC NSs specifically adsorbed onto the positively-charged inflamed colon tissue via electrostatic interaction, leading to efficient therapy of dextran sulfate sodium salt (DSS)-induced colitis. The therapeutic mechanism mainly attributed to decreased ROS levels and pro-inflammatory cytokine secretion, and increased M2-phenotype macrophage infiltration and anti-inflammatory cytokine secretion, efficiently inhibiting inflammation and alleviating colitis symptoms. Due to their excellent ROS-scavenging performance, TiC-based woundplast also promoted skin wound healing and functional vessel formation. Our study introduces redox-mediated antioxidant MXene nanoplatform as a novel type of orally administered nanoagents for treating IBD and other inflammatory diseases of the digestive tract.

The complete structure-functional repair of volumetric muscle loss (VML) remains a giant challenge and biomedical hydrogels to remodel microenvironment and enhance neurogenesis have appeared to be a promising direction. However, the current hydrogels for VML repair hardly achieve these two goals simultaneously due to their insufficient functionality and the challenge in high-cost of bioactive factors. In this study, a facile strategy using NbC MXene-functionalized hydrogel (OPTN) as a bioactive scaffold is proposed to promote VML repair with skeletal muscle regeneration and functional restoration. In vitro experiments show that OPTN scaffold can effectively scavenge reactive oxygen species (ROS), guide macrophages polarization toward M2 phenotype, and resist bacterial infection, providing a favorable microenvironment for myoblasts proliferation as well as the endothelial cells proliferation, migration, and tube formation. More importantly, OPTN scaffold with electroactive feature remarkably boosts myoblasts differentiation and mesenchymal stem cells neural differentiation. Animal experiments further confirm that OPTN scaffold can achieve a prominent structure-functional VML repair by attenuating ROS levels, alleviating inflammation, reducing fibrosis, and facilitating angiogenesis, newborn myotube formation, and neurogenesis. Collectively, this study provides a highly promising and effective strategy for the structure-functional VML repair through designing bioactive multifunctional hydrogel with microenvironment remodeling and enhanced neurogenesis.

Inflammatory responses play a central role in coordinating biomaterial-mediated tissue regeneration. However, precise modulation of dynamic variations in microenvironmental inflammation post-implantation remains challenging. In this study, the traditional β-tricalcium phosphate-based scaffold is remodeled via ultrathin MXene-TiC decoration and Zn/Sr ion-substitution, endowing the scaffold with excellent reactive oxygen species-scavenging ability, near-infrared responsivity, and enhanced mechanical properties. The induction of mild hyperthermia around the implant via periodic near-infrared irradiation facilitates spatiotemporal regulation of inflammatory cytokines secreted by a spectrum of macrophage phenotypes. The process initially amplifies the pro-inflammatory response, then accelerates M1-to-M2 macrophage polarization transition, yielding a satisfactory pattern of osteo-immunomodulation during the natural bone healing process. Later, sustained release of Zn/Sr ions with gradual degradation of the 3D scaffold maintains the favorable reparative M2-dominated immunological microenvironment that supports new bone mineralization. Precise temporal immunoregulation of the bone healing process by the intelligent 3D scaffold enhances bone regeneration in a rat cranial defect model. This strategy paves the way for the application of β-tricalcium phosphate-based materials to guide the dynamic inflammatory and bone tissue responses toward a favorable outcome, making clinical treatment more predictable and durable. The findings also demonstrate that near-infrared irradiation-derived mild hyperthermia is a promising method of immunomodulation.

Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe O , Ti C -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe O /Ti C -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe /Fe into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.

Cancer is a leading cause of human mortality. Given that it is difficult for conventional therapeutic approaches to effectively eradicate tumors and inhibit their recurrence and metastasis, new therapeutic strategies for solving this problem are urgently needed. In this work, we report the development of a two-dimensional titanium carbide nanocomposite drug delivery system. The system can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system. A surface modification engineering strategy has been elaborately designed to realize the multifunctionalization of an MXene, Ti3C2. In this strategy, the nanocomposite drug delivery system (Ti3C2@Met@CP) was established via layer by layer adsorption of metformin (Met) and compound polysaccharide (CP) on the surface of Ti3C2 nanosheets. Among these materials, the synthesized (AlOH)4--functionalized Ti3C2 nanosheets possess strong near-infrared absorption (extinction coefficient of 36.2 L g-1 cm-1), high photothermal conversion efficiency (∼59.6%) and effective singlet oxygen generation (1O2). Compound polysaccharide (CP) is a new immunomodulator formed by mixing lentinan, pachymaran and tremella polysaccharides in optimal proportions. Especially, the decoration of CP onto the Ti3C2 nanosheets endows Ti3C2 with a well-defined shell, improves its tumor site aggregation and biocompatibility, and activates the host's immune functions. The synergistic eradication and inhibition of tumor recurrence and metastasis have been systematically evaluated by in vivo and in vitro experiments.

Near-infrared-II (NIR-II) cancer photothermal therapy (PTT) has become more and more attractive as the NIR-II light shows a higher tissue penetrating depth, which leads to better anti-cancer effects. Recently, the members of the MXene family have been reported as NIR-II photothermal agents, possessing a high specific surface area and a fascinating light-to-heat conversion rate at the same time. Herein, we reported a combination of NIR-II photothermal therapy and immune therapy based on the MXene family member niobium carbide (NbC). First, NbC nanosheets (NSs) under 50 nm were prepared. They showed a high photothermal conversion efficiency under a 1064-nm laser, and the NIR-II light showed a deeper tissue penetration depth. Then, a nanoplatform with high R837 stability and a high loading rate was obtained after modification with a polydopamine (PDA) layer on the surface of NbC. With the R837 modification, the percentage of mature dendritic cells (DCs) increased and the immune response enhanced, compared with the immune response caused by PTT only. Finally, a red blood cell (RBC) membrane was applied as a coat over the nanoplatform in order to avoid excessive blood clearance. During experiments, blood circulation of NbC@PDA-R837@RBC nanoparticles (NPs) was prolonged, and all primary tumors were eliminated. Secondary tumors were also inhibited effectively due to the strengthened immune response, proving that NbC@PDA-R837@RBC NPs could inhibit tumor recurrence. All the results above indicated NbC@PDA-R837@RBC NPs as a potential RBC camouflaged nanoplatform for the combination of effective PTT and immune therapy towards tumor treatment.

Cytokines are essential components of the immune system and are recognized as significant biomarkers. However, detection of a single cytokine is not precise and reliable enough to satisfy the requirements for diagnosis. Herein, we developed a pattern recognition-based method for the multiplexed sensing of cytokines, which involves three-color-emitting boronic acid-decorated carbon dots (BCDs) and arginine-modified titanium carbide (TiC MXenes) as the sensor array. Initially, the fluorescence signals of the three BCDs were quenched by TiC MXenes. In the presence of cytokines, the fluorescence intensity of the BCDs was restored or further quenched by different cytokines. The fluorescence response occurs in two steps: first, boronic acid interacts with -diol functional groups of cytokines, and second, arginine headgroup selectively interacts with glycans. By exploiting the different competing binding of the BCDs and the cytokines toward TiC MXenes, seven cytokines and their mixtures can be effectively discriminated at a concentration of 20 ng mL. Furthermore, our sensor array demonstrated an excellent performance in classifying human oral cancer saliva samples from healthy individuals with clinically relevant specificity. The noninvasive method offers a rapid approach to cytokine analysis, benefiting early and timely clinical diagnosis and treatment.

Peripheral neural interfaces, potent in modulating local and systemic immune responses for disease treatment, face significant challenges due to the peripheral nerves' broad distribution in tissues like the fascia, periosteum, and skin. The incongruity between static electronic components and the dynamic, complex organization of the peripheral nervous system often leads to interface failure, stalling circuit research and clinical applications. To overcome these, we developed a self-assembling, tissue-adaptive electrode composed of a single-component cocktail nanosheet colloid, including dopants, conducting polymers, stabilizers, and an MXene catalyst. Delivered via a jet injector to designated nerve terminals, this assembly utilizes reactive oxygen species to catalytically dope poly (3,4-ethylenedioxythiophene), enhancing π-π interactions between nanosheets, and yielding a conductive, biodegradable interface. This interface effectively regulates local immune activity and promotes sensory and motor nerve functional restoration in nerve-injured mice, while engaging the vagal-adrenal axis in freely moving mice, eliciting catecholamine neurotransmitter release, and suppressing systemic cytokine storms. This innovative strategy specifically targets nerve substructures, bolstering local and systemic immune modulation, and paving the way for the development of self-adaptive dynamic neural interfaces.

Introduction:Lung cancer's high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy. Methods:Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections. Results:The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments. Conclusion:MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.

Two-dimensional transition metal carbides/carbonitrides known as MXenes are rapidly growing as multimodal nanoplatforms in biomedicine. Here, taking SARS-CoV-2 as a model, we explored the antiviral properties and immune-profile of a large panel of four highly stable and well-characterized MXenes - TiCT, TaCT , MoTiCT and NbCT . To start with antiviral assessment, we first selected and deeply analyzed four different SARS-CoV-2 genotypes, common in most countries and carrying the wild type or mutated spike protein. When inhibition of the viral infection was tested in vitro with four viral clades, TiCT in particular, was able to significantly reduce infection only in SARS-CoV-2/clade GR infected Vero E6 cells. This difference in the antiviral activity, among the four viral particles tested, highlights the importance of considering the viral genotypes and mutations while testing antiviral activity of potential drugs and nanomaterials. Among the other MXenes tested, MoTiCT also showed antiviral properties. Proteomic, functional annotation analysis and comparison to the already published SARS-CoV-2 protein interaction map revealed that MXene-treatment exerts specific inhibitory mechanisms. Envisaging future antiviral MXene-based drug nano-formulations and considering the central importance of the immune response to viral infections, the immune impact of MXenes was evaluated on human primary immune cells by flow cytometry and single-cell mass cytometry on 17 distinct immune subpopulations. Moreover, 40 secreted cytokines were analyzed by Luminex technology. MXene immune profiling revealed i) the excellent bio and immune compatibility of the material, as well as the ability of MXene ii) to inhibit monocytes and iii) to reduce the release of pro-inflammatory cytokines, suggesting an anti-inflammatory effect elicited by MXene. We here report a selection of MXenes and viral SARS-CoV-2 genotypes/mutations, a series of the computational, structural and molecular data depicting deeply the SARS-CoV-2 mechanism of inhibition, as well as high dimensional single-cell immune-MXene profiling. Taken together, our results provide a compendium of knowledge for new developments of MXene-based multi-functioning nanosystems as antivirals and immune-modulators.

As the field of cancer therapeutics evolves, integrating two-dimensional (2D) nanomaterials with photo-immunotherapy has emerged as a promising approach with significant potential to augment cancer treatment efficacy. These 2D nanomaterials include graphene-based 2D nanomaterials, 2D MXenes, 2D layered double hydroxides, black phosphorus nanosheets, 2D metal-organic frameworks, and 2D transition metal dichalcogenides. They exhibit high load capacities, multiple functionalization pathways, optimal biocompatibility, and physiological stability. Predominantly, they function as anti-tumor delivery systems, amalgamating diverse therapeutic modalities, most notably phototherapy and immunotherapy, and the former is a recognized non-invasive treatment modality, and the latter represents the most promising anti-cancer strategy presently accessible. Thus, integrating phototherapy and immunotherapy founded on 2D nanomaterials unveils a novel paradigm in the war against cancer. This review delineates the latest developments in 2D nanomaterials as delivery systems for synergistic photo-immunotherapy in cancer treatment. We elaborate on the burgeoning realm of photo-immunotherapy, exploring the interplay between phototherapy and enhanced immune cells, immune response modulation, or immunosuppressive tumor microenvironments. Notably, the strategies to augment photo-immunotherapy have also been discussed. Finally, we discuss the challenges and future perspectives of these 2D nanomaterials in photo-immunotherapy.

Despite the advantages of high tissue penetration depth, selectivity, and non-invasiveness of photothermal therapy for cancer treatment, developing NIR-II photothermal agents with desirable photothermal performance and advanced theranostics ability remains a key challenge. Herein, a universal surface modification strategy is proposed to effectively improve the photothermal performance of vanadium carbide MXene nanosheets (L-VC) with the removal of surface impurity ions and generation of mesopores. Subsequently, MnO coating capable of T1-weighted magnetic resonance imaging can be in situ formed through surface redox reaction on L-VC, and then, stable nanoplatforms (LVM-PEG) under physiological conditions can be obtained after further PEGylation. In the tumor microenvironment irradiated by NIR-II laser, multivalent Mn ions released from LVM-PEG, as a reversible electronic station, can consume the overexpression of glutathione and catalyze a Fenton-like reaction to produce ·OH, resulting in synchronous cellular oxidative damage. Efficient synergistic therapy promotes immunogenic cell death, improving tumor-related immune microenvironment and immunomodulation, and thus, LVM-PEG can demonstrate high accuracy and excellent anticancer efficiency guided by multimodal imaging. As a result, this study provides a new approach for the customization of 2D surface strategies and the study of synergistic therapy mechanisms, highlighting the application of MXene-based materials in the biomedical field.

Influenza A (H1N1) virus is a serious health threat and potential leading cause of death around the world during the processes of immunity and inflammation. Herein a sensitive pH-responsive point-of-care (POC) electrochemical immunoassay was designed for the quantitative monitoring of H1N1 influenza virus using glucose oxidase (GOx) and secondary antibody-functionalized TiC-MXene nanosheets. The assay was carried out on the basis of the sandwich-type immunoreaction in the capture antibody-coated microplate. Two-dimensional (2D) TiC-MXene nanosheets with a large surface area could efficiently enhance the loading amount of GOx molecules, thereby resulting in the signal amplification. Accompanying the formed immunocomplexes, labeled GOx molecules catalyzed glucose into gluconic acid and hydrogen peroxide. The generated gluconic acid caused a pH change of the detection solution, which was quantitatively determined on a handheld pH meter. Two labeling strategies with and without TiC-MXene nanosheets were investigated to determine the target H1N1 influenza virus, and improved properties were acquired with the TiC-MXene-labeled system. Under optimum conditions, the TiC-MXene-based immunoassay gave good dynamic responses toward the target H1N1 influenza virus from 0.01 μg mL to 100 μg mL with a detection limit of 1.3 ng mL. Good reproducibility, high specificity, and acceptable stability were also achieved in the analysis of the target H1N1 influenza virus. Significantly, measurements of the H1N1 influenza virus from clinical human samples were demonstrated to further confirm the method reliability and accuracy of the TiC-MXene-based electrochemical immunoassay. Importantly, such a pH-meter-based immunoassay can be suitable for use in point-of-care applications and opens new opportunities for diagnostics.

Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti C ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4 IFN-γ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4 CD25 FoxP3 regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti C MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.

Effective tissue regeneration and immune responses are essential for the success of biomaterial implantation. Although the interaction between synthetic materials and biological systems is well-recognized, the role of surface topographical cues in regulating the local osteoimmune microenvironment─specifically, their impact on host tissue and immune cells, and their dynamic interactions─remains underexplored. This study addresses this gap by investigating the impact of surface topography on osteogenesis and immunomodulation. We fabricated MXene/hydroxyapatite (HAP)-coated surfaces with controlled 2.5D nano-, submicro-, and microscale topographical patterns using our custom bottom-up patterning method. These engineered surfaces were employed to assess the behavior of osteoblast precursor cells and macrophage polarization. Our results demonstrate that MXene/HAP-coated surfaces with microscale crumpled topography significantly influence osteogenic activity and macrophage polarization: these surfaces notably enhanced osteoblast precursor cell spreading, proliferation, and differentiation and facilitated a shift in macrophages toward an anti-inflammatory, prohealing M2 phenotype. The observed cell responses indicate that the physical cues from the crumpled topographies, combined with the chemical cues from the MXene/HAP coatings, synergistically create a favorable osteoimmune microenvironment. This study presents the first evidence of employing MXene/HAP-multilayer coated surfaces with finely crumpled topography to concurrently facilitate osteogenesis and immunomodulation for improved implant-to-tissue integration. The tunable topographic patterns of these coatings coupled with a facile and scalable fabrication process make them widely applicable for various biomedical purposes. Our results highlight the potential of these multilayer coatings with controlled topography to improve the in vivo performance and fate of implants by modulating the host response at the material interface.

BACKGROUND:Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis. RESULTS:In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (BiMoO-MXene) to induce ferroptosis. A Schottky heterojunction between BiMoO (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron-hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity. CONCLUSION:We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway.

Interleukin-6 (IL-6) is a proinflammatory cytokine with a critical role in immune regulation and treatment of many diseases, including breast cancer. Herein, we developed a novel VCT MXene-based immunosensor for rapid and accurate IL-6 detection. The chosen substrate was VCT, a 2-dimensional (2D) MXene nanomaterial with excellent electronic properties. Prussian blue (Fe[Fe(CN)]), used for its electrochemical properties, and spindle-shaped gold nanoparticles (Au SSNPs), used to combine with antibodies, were in-situ synthesized on the surface of the MXene. The in-situ synthesis ensures a firm chemical connection compared to other tags formed by a less stable physical absorption. Inspired by a sandwich ELISA test, the modified VCT tag was captured by the electrode surface with cysteamine to detect the analyte, IL-6, after being attached with a capture antibody (cAb). Benefiting from an increased surface area, an enhanced charge transfer rate, and a firm connection of the tag, this biosensor exhibited excellent analytical performance. The high sensitivity, high selectivity, and wide detection range covering the IL-6 level of both healthy individuals and breast cancer patients were obtained to meet clinical demands. Herein, this VCT MXene-based immunosensor is a potential therapeutic and diagnostic point-of-care alternative to routine ELISA IL-6 detection methods.

Two-dimensional (2D) materials such as the graphene-based materials, transition metal dichalcogenides, transition metal carbides and nitrides (MXenes), black phosphorus, hexagonal boron nitride, and others have attracted considerable attention due to their unique physicochemical properties. This is true not least in the field of medicine. Understanding the interactions between 2D materials and the immune system is therefore of paramount importance. Furthermore, emerging evidence suggests that 2D materials may interact with microorganisms - pathogens as well as commensal bacteria that dwell in and on our body. We discuss the interplay between 2D materials, the immune system, and the microbial world in order to bring a systems perspective to bear on the biological interactions of 2D materials. The use of 2D materials as vectors for drug delivery and as immune adjuvants in tumor vaccines, and 2D materials to counteract inflammation and promote tissue regeneration, are explored. The bio-corona formation on and biodegradation of 2D materials, and the reciprocal interactions between 2D materials and microorganisms, are also highlighted. Finally, we consider the future challenges pertaining to the biomedical applications of various classes of 2D materials.

Inadequate immune response remains a critical cause of immunotherapy failure in various tumor treatments. Herein, we offer a new approach to achieve a cross-talk between innate and adaptive immune responses based on a new nanoplatform for photothermal therapeutics. The nanoplatform was formed by linking titanium carbide MXene with Mn-contained ovalbumin (OVA), where it can trigger efficient mt-DNA presentation and the release of OVA and Mn upon the irradiation of near-infrared laser. More importantly, the released mt-DNA and Mn synergistically activate innate immunity via the cGAS-stimulator of the interferon genes signaling pathway, and the OVA and protein antigens from tumor cells enhance adaptive immunity. Furthermore, in an osteosarcoma model, we observed that the proposed nanoplatform leads to the effective presentation of tumor antigens, which boost the maturation of dendritic cells (DCs) to the hilt and thus improve the infiltration of cytotoxic T lymphocyte in primary and distant tumors. Collectively, our work not only demonstrates a method for constructing a new nanoplatform for photothermal therapeutics but also provides a general strategy for synchronously activating innate and adaptive immunities to promote the maturation of DCs for antimetastasis tumor therapy.

Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor, but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site. In this work, we report a rational integration of photonic-responsive two-dimensional (2D) ultrathin niobium carbide (NbC) MXene nanosheets (NSs) into the 3D-printed bone-mimetic scaffolds (NBGS) for osteosarcoma treatment. The integrated 2D NbC-MXene NSs feature specific photonic response in the second near-infrared (NIR-II) biowindow with high tissue-penetrating depth, making it highly efficient in killing bone cancer cells. Importantly, Nb-based species released by the biodegradation of NbC MXene can obviously promote the neogenesis and migration of blood vessels in the defect site, which can transport more oxygen, vitamins and energy around the bone defect for the reparative process, and gather more immune cells around the defect site to accelerate the degradation of NBGS. The degradation of NBGS provides sufficient space for the bone remodeling. Besides, calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue. The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered NbC MXene-integrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.

Although vanadium-based metallodrugs are recently explored for their effective anti-inflammatory activity, they frequently cause undesired side effects. Among 2D nanomaterials, transition metal carbides (MXenes) have received substantial attention for their promise as biomedical platforms. It is hypothesized that vanadium immune properties can be extended to MXene compounds. Therefore, vanadium carbide MXene (V C ) is synthetized, evaluating its biocompatibility and intrinsic immunomodulatory effects. By combining multiple experimental approaches in vitro and ex vivo on human primary immune cells, MXene effects on hemolysis, apoptosis, necrosis, activation, and cytokine production are investigated. Furthermore, V C ability is demonstrated to inhibit T cell-dendritic cell interactions, evaluating the modulation of CD40-CD40 ligand interaction, two key costimulatory molecules for immune activation. The material biocompatibility at the single-cell level on 17 human immune cell subpopulations by single-cell mass cytometry is confirmed. Finally, the molecular mechanism underlying V C immune modulation is explored, demonstrating a MXene-mediated downregulation of antigen presentation-associated genes in primary human immune cells. The findings set the basis for further V C investigation and application as a negative modulator of the immune response in inflammatory and autoimmune diseases.

TiC-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a multifunctional nanoplatform based on TiC-MXene-Au nanocomposites, which combines photothermal properties and peroxidase-like activity, accomplishing synergistic photothermal therapy (PTT) and enzyme dynamic therapy (EDT) accompanied by photoacoustic (PA) and thermal dual-mode imaging . Furthermore, PTT induces immunogenic cell death, and EDT promotes cell apoptosis, facilitating dendritic cell (DC) maturation and T cell infiltration into the tumor. On this basis, the antibody OX40 (αOX40) was utilized to further contribute immune therapy for reversing the immunosuppressive tumor microenvironment by activating CD4 and CD8 T cells. In summary, a triune of PTT/EDT/antitumor immune therapy is achieved by combining TiC-MXene-Au nanocomposites and αOX40, which possesses several strong features of good biocompatibility, NIR-controlled targeting, significant cancer cell killing, and satisfactory biosafety and . Our work might highlight the promising application of MXene-based nanoplatforms for cancer therapy.

The repair of diabetic wounds remains challenging, primarily due to the high-glucose-derived immune inhibition which often leads to the excessive inflammatory response, impaired angiogenesis, and heightened susceptibility to infection. However, the means to reduce the immunosuppression and regulate the conversion of M2 phenotype macrophages under a high-glucose microenvironment using advanced biomaterials for diabetic wounds are not yet fully understood. Herein, we report two-dimensional carbide (MXene)-M2 macrophage exosome (Exo) nanohybrids (FM-Exo) for promoting diabetic wound repair by overcoming the high-glucose-derived immune inhibition. FM-Exo showed the sustained release of M2 macrophage-derived exosomes (M2-Exo) up to 7 days and exhibited broad-spectrum antibacterial activity. In the high-glucose microenvironment, relative to the single Exo, FM-Exo could significantly induce the optimized M2a/M2c polarization ratio of macrophages by activating the PI3K/Akt signaling pathway, promoting the proliferation, migration of fibroblasts, and angiogenic ability of endothelial cells. In the diabetic full-thickness wound model, FM-Exo effectively regulated the polarization status of macrophages and promoted their transition to the M2 phenotype, thereby inhibiting inflammation, promoting angiogenesis through VEGF secretion, and improving proper collagen deposition. As a result, the healing process was accelerated, leading to a better healing outcome with reduced scarring. Therefore, this study introduced a promising approach to address diabetic wounds by developing bioactive nanomaterials to regulate immune inhibition in a high-glucose environment.