Electromagnetic pollution and interference have emerged as a critical environmental and technical challenge due to the proliferation of wireless communication, radar, and various electronics. Tailoring interfacial polarization, electron migration, and conductive network through graphitization offers a powerful route to high-efficiency microwave absorbers. Here, we fabricated Fe3O4@Hydrochar core@shell composites via controlled pyrolysis of Hydrochar-coated Fe3O4, enabling precise modulation of carbon shell graphitization and defect density. The high graphitization process could generate a large number of defects, which can produce abundant dipole and enhance the electrical conductivity of composites. Conductive atomic force microscopy imaging and density functional theory simulations demonstrated mechanism that graphitization and defect engineering can effectively tailor the interfacial electronic landscape and enhance electromagnetic-wave attenuation. The Fe3O4@Hydrochar-800 exhibited the minimum reflection loss of -68.95 dB at 10.72 GHz, 4.88 GHz effective absorption bandwidth. The superior absorption property was ascribed to defect-mediated dipole relaxation, intense interface polarization, and impedance-matched conductive loss. The coupling mechanism between graphitization and polarization provided new avenue for fabricating broadband high-performance electromagnetic wave absorbers.
Bone regeneration assisted by synthetic bone substitutes largely depends on the integration of the vascular, neural, and lymphatic systems in the bone. Bone marrow mesenchymal stem cells (BMSCs) are the key cells for this process. However, their role in regulating the integration has not been fully characterized. Human BMSCs (hBMSCs) were treated with osteogenic induction and collected from 0 to 504 h for bulk RNA sequencing (RNA-Seq). Differentially expressed genes (DEGs) were identified and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Time-Series Transcriptomic Trend Analysis were used to comprehensively analyze the possible pathways and functions associated with these DEGs. Weighted Gene Co-expression Network Analysis (WGCNA) was constructed to identify the modules and hub genes of the process. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to validate the expression of key genes identified by RNA-Seq. Time-series analysis of the hBMSCs transcriptome suggested a dynamic expression trajectory during osteogenic differentiation, which was characterized by four functional patterns: the initial adaptation stage (1–24 h), the proliferation activation stage (24–72 h), the differentiation regulation stage (72–336 h) and the remodeling stability stage (336–504 h). Moreover, 72 h was suggested as a potential key time point in the osteogenic–vascular–neural–lymphatic coupling process based on transcriptomic analysis, with typical activation of BMP, vascular endothelial growth factor (VEGF) and PPAR signaling pathways. Four modules and closely related hub genes such as growth differentiation factor 5 (GDF5), matrix Gla protein (MGP) and pregnancy-associated plasma protein A2 (PAPPA2), whose expressions were validated by qRT-PCR and ELISA were also identified and highlighted. Our study revealed the temporal trends of angiogenesis, lymphangiogenesis, and neurogenesis during BMSCs osteogenic differentiation, which not only supplemented the transcriptional regulation in bone regeneration, but also provided a theoretical basis for the design of synthetic bone substitutes.
ABSTRACT Critical‐sized bone defects remain a major clinical challenge in orthopedics and regenerative medicine. Bone organoid provided therapy potentials; however, current engineering strategies generally neglect the bioenergetic foundation and intrinsic mechano‐electrical coupling microenvironment of native bone tissue. Herein, we prepared a three‐dimensional native bone electromechanical niche‐mimicking mechano‐electrical coupling scaffold based on piezoelectric potassium sodium niobate and methacrylated gelatin. Experiments demonstrate that this scaffold establishes an enabling physiologically relevant mechanical–electrical microenvironment throughout organoid construction under dynamic mechanical stimulation, which markedly enhances osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs)and simultaneously endows the engineered organoids with robust pro‐angiogenic and pro‐lymphangiogenic paracrine functions, achieving efficient coordinated regeneration in a rat critical‐sized calvarial defect. RNA‐sequencing together with fluorescent staining proved that mechano‐electrical coupling signals activate the PIEZO1 channel to promote Ca 2+ influx into the cytoplasm and simultaneously upregulate mitochondrial calcium uniporter (MCU) expression, thereby enhancing mitochondrial Ca 2+ . The increased mitochondrial Ca 2 + enrichment promoted tricarboxylic acid cycle enzyme activities and elevated cellular ATP production, which efficiently supports the functional maturation of bone organoids. Overall, this work establishes a bioenergetic engineering construction strategy for bone organoids with enhanced vascular/lymphatic system regeneration, providing both a conceptual framework and an engineering approach for organoid functional optimization and critical‐sized bone defect regenerative treatment.
Post-operative treatment of bone tumors faces a critical clinical dilemma: the need to simultaneously inhibit the tumor while promoting bone regeneration. For this purpose, a multifunctional borate bioactive glass (B-BG) with dynamic pH was designed. In vitro studies indicated, within 2 days, a significant increase in pH up to ∼8.3 was generated to inhibit tumor cells. In the meantime, the increase of surrounding pH generated the formation of apatite-like minerals on the glass surface due to higher supersaturation with respect to hydroxyapatite, thus slow down the degradation rate of B-BG to generate the second stage, a moderate pH range between 7.5 and 8.0, thus increasing the expression of angiogenic genes in HUVECs at 2 days to 2 weeks, and then osteogenic genes in hADSCs after 2 weeks. Such results were further confirmed by implanting B-BG in a mouse CDX osteosarcoma model, a rabbit tumor metastatic model, and a rabbit femoral condyle defect model. The intelligence of such composition indicates the ability to spontaneously meet the surrounding environment respectively tumor inhibition and bone formation. In summary, multifunctional borate bioactive glass (B-BG) may provide a promising strategy for the treatment of bone tumors and the repair of bone defects.
The relationship between the structure of the alkyl chain of organic photothermal agents (PTAs), their ability to form stable nanoparticles, and the resulting efficacy of photothermal therapy (PTT) is unclear, substantially hindering the application of biomimetic PTA-based nanoparticles in PTT. In this study, we designed three Y6-based photothermal molecules with distinct alkyl chain architectures: Y6-0 (no alkyl chain), Y6-nC11 (linear), and Y6-iC11 (branched). Biomimetic nanoparticles incorporating these molecules were constructed (DP@Y6-0, DP@Y6-nC11, and DP@Y6-iC11). The structure-property relationships between the alkyl chain structure, photothermal performance, and storage stability were investigated. Molecules with alkyl chain modifications (Y6-nC11 and Y6-iC11) were found to enhance liposome-binding affinity via hydrophobic interactions. Long alkyl chains promoted more ordered molecular packing, branched side chains (compared to their linear counterparts), and disrupted pi-pi stacking distances, thereby diminishing photothermal performance. Therefore, the DP@Y6-nC11 nanoparticles exhibited a more pronounced redshift in absorption and superior photothermal performance compared to DP@Y6-iC11. Furthermore, fusion with tumor cell membranes significantly enhanced the tumor-specific accumulation of these nanoparticles. Overall, M@DP@Y6-nC11 nanoparticles exhibited excellent photothermal therapeutic efficacy in personalized tumor-specific models.
Implant-associated infections are urgently addressed; however, existing materials are difficult to kill bacteria without damaging cells. Here, we propose an innovative concept of selective antibacterial starvation therapy based on interfering with proton and electron transfer on the bacterial membrane. As a proof-of-principle demonstration, a special Schottky heterojunction film composed of gold and alkaline magnesium-iron mixed metal oxides (Au/MgFe-MMO) was constructed on the titanium implant. Once bacteria contacted this implant, the Au/MgFe-MMO film continuously captured the proton and electron participated in respiratory chain of bacteria to impede their energy metabolism, leading to the deficit of adenosine 5'-triphosphate. Prolonged exposure to this starvation state inhibited numerous biosynthesis processes and triggered severe oxidative stress in bacteria, ultimately leading to their death due to DNA and membrane damage. In addition, this heterojunction film was comfortable for mammalian cells, without inhibiting mitochondrial function. This proposed starvation antibacterial therapy gives a notable perspective in designing biosafe smart antibacterial biomaterials.
Biodegradable zinc-based metals have received attention due to their strength, biodegradability, and desirable biocompatibility. However, the trade-off between strength and ductility has limited their use. Here, we designed a biodegradable Zn-Li-Mn ternary alloy with superior strength and ductility. The ultimate tensile strength (UTS) of Zn-0.4Li-xMn (x = 0.1, 0.4, and 0.8) alloys reached 438.74-469.96 MPa, similar to pure Ti, with elongation reaching 41.52%-54.91%, surpassing other Zn-Li-based alloys. We investigated the biodegradation behavior and osteogenic effects of the Zn-Li-Mn alloys both in vitro and in vivo. Immersion tests demonstrated that the alloys exhibited a more uniform degradation morphology with significantly less release of Zn2+ ion compared to pure Zn. Cytocompatibility, hemocompatibility, and histological analyses demonstrated their biosafety. In addition, Zn-Li-Mn alloy extracts significantly enhanced osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs), manifesting higher alkaline phosphatase activity, increased biomineralization, and elevated osteogenic gene expression. Zn-0.4Li-0.8Mn alloy showed the highest osteogenic activity in vitro. When implanted in rat femoral condyles, it demonstrated improved in vivo bone regeneration effects, exhibiting enhanced osteointegration. Transcriptomic analysis revealed that Zn2+, Mn2+, and Li+ ions released from Zn-Li-Mn alloy collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, prompting osteogenic differentiation. These findings demonstrate the high potential of the Zn-0.4Li-0.8Mn alloy for bone implants. STATEMENT OF SIGNIFICANCE: 1. Biodegradable Zn-Li-Mn ternary alloy with superior mechanical strength and excellent ductility were designed. 2. Enhanced osteointegration were observed in Zn-0.4Li-0.8Mn implants in vivo. 3. Transcriptomic analysis revealed that the Zn2+, Mn2+, and Li+ released from Zn-0.4Li-0.8Mn collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, enhancing osteogenesis.
The poor mechanical properties of pure zinc (Zn) restrain its applications in orthopedics, which requires high loading capacity. Alloying with lithium (Li) element can enhance strength, however, the workhardening rate is impaired with increased Li content. Here, introducing scandium (Sc) into a low Li- containing Zn-0.1Li alloy could effectively refine its microstructure, reducing the average grain size from 10 to 4 }m. The refinement in microstructure led to a significant improvement in tensile strength, improving from 257 MPa of Zn-0.1Li to 341 MPa of Zn-0.1Li-0.1Sc, meanwhile, the work-hardening rate remained positive during the whole plastic deformation stage. The addition of Sc-impaired elongation is due to numerous microcracks formed at the Zn/ScZn12 interfaces, as well as in the large-sized ScZn12 particles. Corrosion tests revealed an accelerated corrosion rate due to the galvanic effect between the Zn matrix and ScZn12 phase. Even so, the Zn-0.1Li-1.0Sc alloy still exhibited superior biocompatibility with rat/mouse mesenchymal stem cells and close osteogenesis capacity to the original Zn-0.1Li alloy. These findings demonstrated that the addition of Sc in low Li-containing alloys could improve mechanical strength without sacrificing the work-hardening rate and biocompatibility. (c) 2025 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.
Myocardial ischemia/reperfusion (I/R) injury represents a major global health concern, driven by excessive reactive oxygen species (ROS), which closely correlates with subsequent myocardial infarction and fibrosis. Combining ROS scavenging with ischemic myocardium revascularization holds therapeutic promise. However, developing multifunctional therapeutic agents that can simultaneously scavenge ROS and promote angiogenesis remains unreported. Herein, we propose MgSrCeAl-layered double hydroxide (LDH) nanosheets as a multifunctional ROS scavenger and angiogenesis promoter for efficient myocardial I/R injury treatment. MgSrCeAl-LDH nanosheets not only exhibit exceptional hydroxyl radicals (·OH) and superoxide anions (·O2−) scavenging capabilities, which is 1.78 times and 1.61 times that of CeO2, respectively, but also respond to the ischemia-induced acidic microenvironment to release angiogenic Sr2+ with a concentration of 32.65 ppm (pH 5.0), which is conducive to efficient angiogenesis. Specifically, the ROS levels in I/R-injured myocardium decreased to 66.2
Effective treatment of intervertebral disc degeneration with biomaterials remains a challenge, owing to the difficulty in simultaneously overcoming oxidative stress and its associated cascades in the nucleus pulposus microenvironment, which includes cellular senescence, apoptosis, inflammation, and extracellular matrix (ECM) degradation. To address these issues, a multifunctional hydrogel (HG-QNT) loaded with transforming growth factor- beta 1 (TGF- beta 1) and quercetin-based nanoparticles (QUNPs) is developed through borate ester bonding and Schiff base reaction-induced crosslinking. Specifically, QUNPs fabricated via coordination and hydrophobic interactions endow the hydrogel with extraordinary antioxidative properties. Benefiting from the multi-dynamic crosslinking, the hydrogel achieves self-healing, mechanical stability, and pH-responsive release of QUNPs and TGF- beta 1. The HG-QNT hydrogel is demonstrated to enhance the proliferation of encapsulated nucleus pulposus cells, thereby providing an ideal platform for cell transplantation. The cooperative antioxidation of QUNPs and the hydrogel carrier renders HG-QNT effective in mitigating oxidative stress, resulting in the suppression of cellular senescence, mitochondrial dysfunction, apoptosis, excessive inflammation, and abnormal catabolism. Afterwards, TGF- beta 1 and QUNPs act in synergy with the hydrogel to restore the anabolic/catabolic balance by enhancing ECM synthesis. Overall, the strategy orchestrating multiple modulation by HG-QNT hydrogel shows great potential for application in intervertebral disc regeneration. (c) 2025 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.
The repair of multiple organs in motor systems remains a major clinical challenge that necessitates bioactive grafts with a multidirectional differentiation ability. Hydrogel-based organoids implants have emerged as pivotal tools and attracted great attentions. However, strategies to unlock the multipotency of bone marrow mesenchymal stem cells (BMSCs) by precisely modulating the mechanical and structural characteristics of biomimetic extracellular matrix (ECM) during hydrogel-based organoid construction remain underexplored. In this study, a gelatin methacryloyl (GelMA)-based biomimetic ECM mimic hydrogel (HG-2) loaded with BMSCs was developed to construct a multidirectional differentiation organoid, HG-2/3d-BMSC. The hydrogel could provide spatial mechanical stimulation to adherent BMSCs via cell adhesion induced cytoskeleton assembly. RNA sequencing (RNA-Seq) combined with in vitro and in vivo biological experiments reveals that ECM mimic hydrogels deliver adhesion-based spatial mechanical stimulation. This mechanical stimulation specifically unlocks the multipotency of BMSCs during osteogenic differentiation induction. Furthermore, it accelerates and enhances the multidirectional differentiation capacity of BMSCs, simultaneously promoting their commitment to osteogenic, chondrogenic, and tendonogenic tissue lineages. Further investigations prove that adhesion-based spatial mechanical stimulation from the ECM mimic hydrogel enhances multidirectional differentiation of BMSCs-based organoid via Yap/Tead4 (yes-associated protein/TEA domain transcription factor 4) mechanotransduction mediated Kat7 downregulation. The work not only advances the theoretical framework for designing biomaterials that exploit mechanical cues to override biochemical-driven lineage commitment but also establishes a novel paradigm for developing multifunctional organoid constructs to address the clinical challenge of regenerating hierarchically complex tissues in a motor system.
Pathogenic infections and volatile organic compounds (VOCs) with low concentration but high toxicity imperil heavily the health of people. Herein, we developed a green and eco-friendly photocatalytic multifunctional material of CeO2/ZnMn2O4 by in-situ hydrothermal growth of ZnMn2O4 on CeO2, which can not only kill bacteria rapidly but also eradicate formaldehyde effectively. In vitro antibacterial test disclosed that after 35 min of irradiation with 300 W xenon lamp, CeO2/ZnMn2O4 composite can kill 99.85 % Staphylococcus aureus (S. aureus) and 97.84 % Escherichia coli (E. coli). Meanwhile, the synthesized CeO2/ZnMn2O4 composite can degrade 91.35 % formaldehyde within 60 min under simulated light irradiation (0.1 W/cm2). The underlying mechanism stems from the heterojunction interface formed between CeO2 and ZnMn2O4, which accelerates the transfer and separation of photo-excited electron-hole pairs, thereby enhancing reactive oxygen species (ROS) generation. Driven by the heterojunction's synergistic photothermal-oxidative mechanisms, the generated ROS disrupt bacterial membranes via oxidative damage, achieving effective bactericidal efficacy. Simultaneously under light activation, formaldehyde adsorbed on the composite surface undergoes ROS-mediated mineralization, converting this toxic pollutant into innocuous byproducts such as CO2 and H2O.
Contact infection is accelerating the spread of pathogenic bacteria, threatening the health of people all over the world. Herein, photoresponsive TiO 2 /N‐doped ZnO (TiO 2 /N‐ZnO) nanofilms are synthesized using atomic layer deposition and the sol–gel method to rapidly kill bacteria on electronic touch screens by strengthened photocatalytic sterilization. The enhancement of the photocatalytic performance of TiO 2 /ZnO is significantly attributed to the oxygen vacancy and crystal defect induced by nitrogen element doping, leading to the production of an increased quantity of reactive oxygen species from TiO 2 /N‐ZnO. Further, when bacteria engage with the nanofilm, there is an occurrence of electron transfer between the TiO 2 /N‐ZnO and the bacterial film, thereby consequently disturbing the electron equilibrium on the bacterial film. Upon exposure to simulated sunlight for a duration of 3 min (for Staphylococcus aureus ; S. aureus ) or 10 min (for Escherichia coli ; E. coli ), TiO 2 /N‐ZnO demonstrates superior antibacterial effects (>95%) on both bacterial strains. With the illumination time extended to 20 min, the antibacterial efficacy of TiO 2 /N‐ZnO against S. aureus and E. coli reaches up to 100%. Concurrently, the TiO 2 /N‐ZnO nanofilms demonstrate commendable light transmittance (>85%) and biocompatibility. As such, this study may offer a potential methodology for antimicrobial applications in electronic touch screens.
Titanium alloys with good antibacterial properties and low elastic modulus have great potentials for biomedical application. Ti-13Nb-13Zr-xAg(x = 7,10) alloys were prepared to reveal the influence of Ag content on the microstructure, corrosion resistance, elastic modulus and antibacterial property. The results have shown that the decrease in the Ag content promoted the precipitation of Ti2Ag phase, thereby improving the antibacterial properties and reducing the elastic modulus of the material. Ti-13Nb-13Zr-10Ag achieved the high corrosion resistance, good antibacterial properties and low elastic modulus.
Antibacterial coatings that can firstly prevent bacterial adhesion and then kill the attached bacteria are urgently required for combat of implant-associated infections. However, current surface strategies are limited by complicated preparation, uncontrolled-release of antimicrobials, and low biocompatibility. Here, we developed a dual-functional, antibacterial coating by functionalizing iron oxide nanoparticles (FNP) with polydopamine and polyethylene glycol, and then depositing them with silk fibroin (SF) on a titanium substrate (FNP/SF-Ti). This surface strategy is facile to achieve and widely adapted to any nanoparticles and substrates. In an optimized SF coating density, the FNP/SF-Ti surface reduced bacterial adhesion for more than 100 folds to both Methicillinresistant Staphylococcus aureus and Escherichia coli to compare with bare Ti surface. Under near-infrared (NIR) light irradiation, the attached bacteria on FNP/SF-Ti surface were totally killed in a photo-controllable way and no biofilm formed subsequently. The in vitro biocompatibility and osteogenic effect of FNP/SF-Ti surface was better than bare Ti and FNP-Ti surface. In a rat sub-cutaneous model, MRSA infections on FNP/SF coated Ti discs were effectively inhibited due to the synergistically effect of anti-adhesive and photothermal performances. In a rat bone-defect model, MRSA-contaminated FNP/SF-Ti rods were disinfected by NIR irradiation after implantation and the osteogenesis on FNP/SF-Ti rods were not affected by MRSA infection. Therefore, the FNP/SF coating is a potential surface treatment strategy to prevent implant-associated infections.
Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.
Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries. Tissue engineering is another milestone in the developmental history of life science after cellular and molecular bioscience. Nevertheless, despite decades of rapid development, tissue-engineered biomaterials have not been widely used clinically. Biomaterials constructed by physical and chemical methods have lots of difficulty in precisely mimicking the macroscopic and microscopic structures of human tissues. The ultimate way to build organoid tissue for regeneration is to enable the cells to take the initiative and build suitable functions. Based on the thoughts of tissue engineering, organoid technology holds great potential as a research tool for a wide range of fields, including developmental biology, disease pathology, cell biology, precision medicine, and drug toxicity and efficacy testing. This technology also holds tremendous potential for regenerative medicine, as organoids present the possibility for autologous and allogeneic cell therapy through the replacement of damaged or diseased tissues with organoid-propagated tissue or stem cell populations. In this review work, we briefly outlook the development history of organoid technology, summarize the current bottlenecks and the underlying reasons, and propose the unified term “function-oriented design in tissue engineering”, a new topic that may provide a solution to overcome these bottlenecks.