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Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment. Graphical abstract

Bone regeneration is mediated by paracrine signaling, with extracellular vesicles (EVs) playing a crucial role as communication mediators. Previous studies have shown that there are differences in the performance of the bone marrow mesenchymal stem cells (BMSCs) derived from the mandible and limbs. However, it is not clear whether there are differences in EVs originating from them. In this study, we demonstrated that compared to EVs derived from limbs, the EVs derived from the mandible were more effective in stimulating BMSCs migration, proliferation, osteogenic differentiation in vitro , and bone regeneration in vivo . Upregulated miRNAs in EVs from mandible target signaling pathways such as MAPK, Wnt, and Hippo, which have been shown to be crucial for bone formation. Therefore, it may be an excellent candidate for improving bone healing in autologous bone transplantation, bone tissue engineering, or other bone diseases.

The dressing that promotes scarless healing is essential for both normal function and aesthetics after a wound. With a deeper understanding of the mechanisms involved in scar formation during the wound healing process, the ideal dressing becomes clearer and more promising. For instance, the yes‐associated transcriptional regulator (YAP) has been extensively studied as a key gene involved in regulating scar formation. However, there has been limited attention given to pectolinarin, a natural flavonoid that may exhibit strong binding affinity to YAP, in the context of scarless healing. In this study, we successfully developed a temperature‐sensitive Pluronic@F‐127 hydrogel as a platform for delivering pectolinarin to promote scarless wound healing. The bioactive pectolinarin was released from the hydrogel, effectively enhancing endothelial cell migration, proliferation and the expression of angiogenesis‐related genes. Additionally, a concentration of 20 μg/mL of pectolinarin demonstrated remarkable antioxidant ability, capable of counteracting the detrimental effects of reactive oxygen species (ROS). Our results from rat wound healing models demonstrated that the hydrogel accelerated wound healing, promoting re‐epithelialization and facilitating skin appendage regeneration. Furthermore, we discovered that a concentration of 50 μg/mL of pectolinarin incorporated to the hydrogel exhibited the most favourable outcomes in terms of promoting wound healing and minimizing scar formation. Overall, our study highlights that the significant potential of locally released pectolinarin might substantially inhibit YAP and promoting scarless wound healing.

The Hox gene plays a crucial role in the bone development, determining their structure and morphology. Limb bone grafts expressing Hox positive genes are commonly used for free transplantation to repair Hox negative mandibular critical bone defects. However, the specific role of original Hox genes in newly formed bone during the cross‐layer bone grafting healing process remains unexplored. Our findings demonstrate that femurs ectopically grafted into the mandibular environment retained a significant ability to differentiate into cartilage and form cartilaginous callus, which may be a key factor contributing to differences in bone graft healing. Hoxc10, an embryonic layer‐specific genes, regulates cartilage formation during bone healing. Mechanistically, we observed Hoxc10 retention in co‐cultured femoral BMSCs. Knocking out Hoxc10 narrows the bone gap and reduces cartilage formation. In summary, we reveal Hoxc10's ‘positional memory’ after adult cross‐layer bone graft, influencing the outcomes of autologous bone graft.

Oral squamous cell carcinoma (OSCC) is a prevalent and deadly cancer, with over 350,000 new cases yearly. A hypoxic tumor microenvironment is the bottleneck of photodynamic therapy (PDT) and significantly weakens overall therapeutic efficacy. In this study, we introduce nitrogen vacancy-modified PCN (N -PCN), a novel metal-free and O -independent photosensitizer designed for PDT. N -PCN targets Cal-27-induced OSCC by reducing highly expressed H O in tumors to highly reactive •OH. This innovative approach aims to overcome the limitations posed by the hypoxic environment and enhance the effectiveness of PDT in treating OSCC. The introduction of N not only further improves the cell accessibility of PCN by increasing the content of -NH but also provides more reactive sites for H O reduction and facilitates carrier separation. Under illumination, N -PCN generates a burst of •OH around the nuclei and mitochondria of Cal-27 cells, which effectively kills the cells via synchronously leading to DNA damage and mitochondrial dysfunction. Compared to the conventional photosensitizer chlorin e6, N -PCN-based PDT exhibits excellent anticancer performance in vitro and in vivo, highlighting its potential as a next-generation therapeutic agent. Collectively, the high •OH-generation efficiency, strong anticancer activity, and overall safety of the O -independent nanoparticle opens up new avenues for in-depth study on carbon nitride-based cancer PDT strategies. This work offers new hope for the effective treatment of OSCC and other challenging cancers.

Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action. The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry. The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting. This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state.

TLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response. Innate immune cells respond to a number of environmental cues including TLR signalling. Here the authors implicate mechanical sensor Piezo1 in the TLR4 mediated host response to bacterial infection and implicate it in the enhancement of macrophage mediated host response.

Beneficial from the excellent optical performance of zinc oxide (ZnO) nanocrystals and the absorption properties of graphene oxide (GO), the nanocomposites of ZnO and GO with synergistic photocatalytic effects were prepared by a precipitation method, in which GO is utilized as the catalyst carrier. The prepared composites were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy and also performed photocatalytic activity for the nanocomposites. The results show that ZnO is uniformly loaded on the surface of GO assisted by an effective interface coupling. Due to interface coupling between ZnO and GO, electrons can be directly transferred from the valence band of ZnO to GO. The photodegradation efficiency of the composites reaches to 97.6%, and the first-order reaction rate constant of photodegradation is calculated to be 0.04401 min-1. The novel ZnO-GO composites with excellent photocatalytic performance display promising potential applications in the field of photocatalysis and will provide a new platform for building next-generation graphene-based semiconductor composites.

Iron carbide catalysts, particularly the Fe 7 C 3 phase, hold significant potential for efficient CO 2 hydrogenation to olefins, yet stabilizing this phase under reactive conditions remains a major challenge. Herein, we report a robust and efficient synthesis of nearly phase-pure Fe 7 C 3 catalysts derived from Prussian blue analogues, whose stability is significantly enhanced by strategically incorporating K and Mg promoters. Comprehensive characterization reveals that K accelerates the carbonization process and markedly enhances olefin selectivity, whereas Mg effectively suppresses water-induced oxidation, preserving the structural integrity of the Fe 7 C 3 phase. Under optimized reaction conditions (340 °C, 2 MPa, H 2 /CO 2  = 3), the Fe 7 C 3 -KMg catalyst achieves a high CO 2 conversion of 41.5% and an olefin selectivity of 67.1%, maintaining exceptional catalytic stability for over 1000 hours. These findings offer valuable new insights into the rational design of robust iron carbide catalysts for sustainable and efficient CO 2 conversion into high-value chemicals. Iron carbide catalysts—especially the Fe 7 C 3 ; phase—show great promise for efficient CO 2 hydrogenation to olefins. Here, the authors report the first stable, nearly pure Fe 7 C 3 catalyst for CO 2 -to-olefins conversion, overturning conventional models that posit the necessity of Fe 5 C 2 –Fe 3 O 4 coexistence.

To address the challenging issues of metal materials corrosion in industries, which has caused huge economic losses and security threats to many facilities in marine environments, functional polymer coatings have been widely used and regarded as one of the simplest and most effective methods to prevent such an undesirable event. In this study, a new type of coating filler consisting of graphene oxide/polyaniline/polydopamine (GO-PANI-PDA) nanocomposites has been successfully synthesized. The morphology, structure, composition, and corrosion resistance performance of the GO-PANI-PDA (GPP) nanocomposites were investigated via a series of characterization methods. The results from our electrochemical impedance spectroscopy, potentiodynamic polarization curve and salt spray experiment showed that the best corrosion resistance performance of the coating is from GPP 21 with the epoxy/GO-PANI:PDA ratio of 2:1, which exhibited a positive corrosion potential (−0.51 V) shift from epoxy/GO-PANI coating (−0.64 V). The corrosion current density (3.83 × 10−8 A/cm2) of GPP 21 is nearly an order of magnitude lower than that of epoxy/GO-PANI (7.05 × 10−7 A/cm2). The good anti-corrosion performance was fascinatingly observed in salt spray tests even without obvious corrosion phenomenon after 30 days of testing. Due to these remarkable properties, GPP nanocomposites can be an outstanding candidate for the rapid development of broadband shielding and anticorrosive materials.