Biomaterials research最新文献

Mesoporous metal nanomaterials (MMNs) have gained interest in biomedicine for their unique properties, but their potential is limited by the predominance of spherical shapes and the neglect of morphological effects on biological activity, which hinders the reasonable evaluation of morphology-dependent enzyme-like activities and biological behaviors and its further biomedical applications. It is therefore imperative to find an effective and facile method to design and prepare MMNs with novel, well-defined morphologies. Herein, we fabricated 3 mesoporous platinum nanoenzymes including sphere, rod, and bipyramid topologies [Au@mesoPt sphere, Au@mesoPt rod, and Au@mesoPt bipyramid nanoparticles (NPs), respectively] via a facile atomic layer deposition method using gold NPs (Au NPs) as the templated cores and Pluronic F127 as a structure-directing agent. The obtained Au@mesoPt NPs could enhance cellular uptake efficiency and prolong blood elimination half-lives, which helped more cancer cell spheroid permeation and accumulation at the disease sites post-injection. Au@mesoPt NPs could obviously alleviate atherosclerosis through reactive oxide species (ROS) scavenge due to its catalase-like activity and inhibition of pro-inflammatory cytokine release. Due to the role of metal nanoenzymes containing high-order-number (Z) elements as radiosensitizers, Au@mesoPt NPs have a distinct radiosensitizing on pancreatic cancer treatment. Among the shapes, Au@mesoPt bipyramids showed the best therapeutic efficacy in treating atherosclerosis and pancreatic cancer, likely due to their high aspect ratio, irregular surface, and anisotropy, which favor blood flow and cellular uptake. The tunable synthesis of shape-defined MMNs bodes well for other areas of application, including biosensors, surface-enhanced Raman scattering, surface plasmon resonance, hydrogen storage, catalysis, and electrotherapy.

Cancer is a devastating disease, and its pathogenesis is highly associated with malnutrition and poor lifestyle. Chemotherapy continuously causes inadequate therapeutic efficacy and induces off-target toxicities. Hence, targeted co-administration of chemotherapy and dietary supplement producing anticancer effect at low doses with minimized toxicities would be a promising strategy for cancer treatment. In this study, we constructed chondroitin sulfate (CS) and methotrexate (MTX) carried serum albumin nanocages (C/M@Alb NCs) by albumin nanoreactor strategy. During fabrication, we achieved the precipitation of MTX and CS inside the albumin nanocore under mild reaction condition to prepare C/M@Alb NCs. The enhanced anticancer efficacy of C/M@Alb NCs was comprehensively assessed by in vitro and in vivo experiments. Biodistribution, pharmacokinetic profile, and in vivo therapeutic efficacy of C/M@Alb NCs were investigated in human colorectal adenocarcinoma (HT-29), murine breast cancer (E0071), and patient-derived (PDX) lung cancer models. The as-prepared C/M@Alb NCs facilitated higher MTX and CS encapsulation, exhibiting small particle size, improved colloidal stability, dual stimuli (pH/GSH)-responsive drug release profile, an enhanced cellular uptake, cooperative synergistic cytotoxicity, extended blood residence time, improved lymph node and tumor targeting, and in vivo therapeutic efficacy against various cancers such as human colorectal adenocarcinoma, murine breast cancer, and patient-derived (PDX) lung cancer. Altogether, C/M@Alb NCs exhibited enhanced cellular uptake, extended blood residence time, and favorable tumor accumulation and lymph node extravasation, finally leading to the potent antitumor efficacy against various cancers. This nanoplatform offers a new strategy for designing lymph node- and cancer-targeted albumin-based nanomedicine for clinical applications.

The utilization of mesenchymal stem cells (MSCs) serves as an encouraging strategy for treating liver fibrosis. However, precise mechanisms are not completely understood. Recently, small extracellular vesicles (sEVs) have emerged as major paracrine effectors mediating the anti-fibrotic effects of MSCs. This study seeks to examine the healing properties of MSCs-sEVs on liver fibrosis and decipher the associated signaling pathways. Herein, MSCs substantially ameliorated carbon tetrachloride (CCL4)-induced liver inflammation and fibrosis in mice, with this effect predominantly attributed to their derived sEVs. Both in vivo and in vitro experiments verified that MSCs-sEVs skewed the phenotype of liver macrophages into an anti-fibrotic phenotype. Mass spectrometry analysis showed that ubiquitin-specific peptidase 10 (USP10) was significantly enriched in MSCs-sEVs, which was critical for protection against liver fibrosis. USP10 stabilizes Krüppel-like factor 4 (KLF4) via deubiquitination, participating in the modulation of macrophage phenotypes. Mechanistically, KLF4 reprograms macrophages to enhance their anti-inflammatory and repairing functions by modulating NF-κB/STAT6 signaling and regulating the transcription of MMP12. Finally, the exogenous incorporation of USP10 into MSCs-sEVs via genetic engineering further potentiated their antifibrotic effects. These findings deepen the knowledge regarding the cellular pathways through which MSCs ameliorate liver fibrosis, offering a theoretical basis for sEV-based therapeutic strategies.

Patient-derived tumor xenograft (PDX) models serve as powerful tools in oncology research owing to their ability to capture patient-specific tumor heterogeneity and clinical behavior. However, the conventional matrices derived from murine tumors, commonly used to generate PDX models, suffer from key limitations such as lack of tissue specificity, high production costs, and inconsistent batch quality. In response, our study investigates the use of decellularized liver extracellular matrix (Liver ECM) as a biomimetic alternative that more accurately recapitulates the native hepatic microenvironment. We demonstrate that Liver ECM, enriched with liver-specific biochemical cues, enables robust engraftment, growth, and metastasis of patient-derived hepatocellular carcinoma cells in both subcutaneous and orthotopic PDX models. Notably, orthotopic models established with Liver ECM exhibited enhanced metastatic behavior, particularly to the intestine, compared to those formed using conventional matrices. Transcriptomic analysis further revealed activation of key pathways associated with cancer progression, including angiogenesis, apoptosis, migration, and inflammation. Additionally, we extend the application of Liver ECM to patient-derived organoid xenografts, which showed improved tumorigenicity and retained pathophysiological features of the original tumor tissue. Together, these findings underscore the potential of liver-specific ECM as a superior platform for generating physiologically relevant PDX models and enhancing the translational relevance of preclinical cancer studies.

As lung cancer is still the deadliest cancer worldwide, there is an urgent need for safer and more efficient therapies. This study aims to address the challenges posed by tumors in reducing the efficacy of sonodynamic therapy (SDT) through mechanisms such as hypoxia and abnormal blood vessel formations. In this study, manganese-containing DNA nanoflowers (DHA-DDF) loaded with doxorubicin (DOX) were functionalized with an AS1411 aptamer and a hypoxia-inducible factor-1α (HIF-1α) antisense sequence. The in vitro tests confirmed their stability and pH-responsive drug release properties. The combined treatment of DHA-DDF and ultrasound could induce apoptosis, inhibit the migration and invasion of Lewis lung carcinoma (LLC) cells, and down-regulate the expression of HIF-1α and VEGF in LLC cells. The in vivo studies using subcutaneous LLC in mice showed that ultrasound enhanced the tumor-targeted accumulation and penetration of DHA-DDF. The combined approach markedly reduced tumor development and extended the survival of tumor-bearing mice, effectively down-regulated the expression of hypoxia-related genes, inhibited cell proliferation, and blocked tumor angiogenesis. The programmable, biocompatible, and multifunctional nanoflowers demonstrate a notable improvement in the efficacy of SDT and provide robust tumor inhibition in both cellular and animal models. The findings highlight the potential of DNA nanotechnology in advancing innovative cancer therapies.

Bone graft substitutes are commonly used to repair large bone defect, and restoring the alveolar bone defects in height and width is a major challenge in restorative dentistry. In comparison with clinic bone graft substitutes such as bovine-derived powder and hydroxyapatite, demineralized dentin matrix (DDM) is a valuable alternative due to its compositional similarity to human-derived bone. However, a challenge remains in using DDM for bone rehabilitation, particularly in maintaining spatial morphology due to its granular form. This study developed an effective bone graft substitute using DDM particles in a fast-cured silk fibroin/hyaluronic acid methacrylate (SF/HAMA) hydrogel, which adheres well to the alveolar bone defect and rapidly gels under blue light. In vitro and in vivo experiments were performed to evaluate the biocompatibility of this hybrid hydrogel. The ability to repair bone defects was tested on cranial defects in rats and mandibular defects in beagles. Results showed that the in situ composites exhibited excellent mechanical strength and biocompatibility, with micro-computed tomography and histology confirming the best bone regeneration effect of the SF/HAMA/DDM-50 hybrid hydrogel. This composited bone graft substitute could provide a novel strategy for the clinical treatment of alveolar bone defects and is a promising candidate for bone tissue reconstruction and regeneration.

Biological dressings have emerged as a promising approach for effective wound treatment. However, despite extensive research, the fabrication of biomass-based dressings with antioxidant and anti-inflammatory properties, as well as high biocompatibility, remains a challenge. In this study, the byproducts of Andrias davidianus as raw materials were used to prepare a biomass-based Pickering emulsion. A stable emulsion was formed by homogenizing A. davidianus collagen (AD-SC) with liver oil (AD-LO). The antioxidant peptides (AD-BP) were then incorporated into the mixture, and a Pickering emulsion loaded with antioxidant peptides was successfully prepared. The stability of AD-PE was confirmed through storage, centrifugation, and ζ-potential analyses, and the emulsion exhibited the controlled release of the peptides. In vitro experiments confirmed that AD-PE exhibited marked antioxidant activity and high biocompatibility, with no cytotoxicity, and the promotion of cell migration. In addition, in vivo evaluations demonstrated that AD-PE accelerated wound healing by leveraging the synergistic effects of its components to reduce inflammation and mitigate oxidative damage. This work offers a novel approach for the biomedical application of AD-PE and a new strategy for the utilization of A. davidianus processing byproducts.

Radiotherapy is pivotal in localized cancer treatment, yet balancing therapeutic efficacy with collateral tissue damage remains challenging. Conventional iodinated contrast agents, limited by rapid metabolism and short imaging windows, hinder precise radiotherapy planning. We developed IR808-ATIPA, a tumor microenvironment-responsive iodine-based compound integrating computed tomography (CT) imaging and radiosensitization. Synthesized by covalently linking IR808 and ATIPA, IR808-ATIPA leverages iodine's x-ray attenuation for high-contrast imaging while enhancing radiation dose deposition in cervical cancer. Unlike conventional agents, its prolonged tumor retention improves imaging accuracy and therapeutic targeting. Evaluations in HeLa tumor-bearing nude mice demonstrated superior in vitro/in vivo imaging performance and sustained tumor accumulation. RNA sequencing revealed that IR808-ATIPA enhances radiotherapy efficacy by activating the ferroptosis pathway via increased reactive oxygen species production and amplified x-ray absorption. Safety assessments confirmed no notable toxicity to major organs. IR808-ATIPA functions dually as a CT contrast agent for precise tumor delineation and a radiosensitizer promoting ferroptosis-mediated radiotherapy enhancement. Its extended intratumoral retention enables targeted therapy, minimizing off-target effects. These findings highlight IR808-ATIPA as a promising theranostic agent, bridging imaging-guided precision and therapeutic efficacy to advance personalized cancer treatment.

Ferroptosis, a form of lipid peroxidation-mediated cell death, plays a critical role in acute kidney injury (AKI) progression. Tripterine is an active component isolated from traditional medicinal herbs and exhibits diverse biological and pharmacological activities. However, poor bioavailability and cytotoxicity of tripterine has limited its further clinical application, and the underlying action mechanism of tripterine against AKI remains largely unknown. This study aimed to overcome these shortcomings by formulating tripterine into selenized phytosomes and to investigate the therapeutic effects of selenized tripterine phytosomes (Se@Tri-PTs) on ferroptosis-associated AKI. The data showed that Se@Tri-PTs improved the antioxidant capacity of tripterine while reducing its cytotoxicity. Upon erastin or RSL3 stimulation, Se@Tri-PTs maintained intracellular glutathione levels, decreased lipid ROS generation, and suppressed ferroptosis. Mechanistically, Se@Tri-PTs blocked autophagy-mediated degradation of glutathione peroxidase 4 (GPX4), thereby suppressing ferroptosis. Furthermore, Se@Tri-PTs maintained dual-specificity protein phosphatase 1 (DUSP1) protein levels in erastin-stimulated cells, and DUSP1 knockdown reversed Se@Tri-PTs-mediated inhibition of autophagy and ferroptosis. In line with in vitro results, Se@Tri-PTs administration obviously attenuated folic acid-induced AKI and autophagy-dependent ferroptosis in mice. Collectively, these results indicated that Se@Tri-PTs ameliorated ferroptosis and AKI by preserving DUSP1 levels to block autophagy-mediated degradation of GPX4, highlighting their potential in treating ferroptosis-related diseases.

Bioactive hydrogels have garnered considerable attention for endogenous tissue regeneration owing to their affordability, minimal regulatory barriers, and ability to harness the body's intrinsic healing potential. Recently, inorganic-ion-releasing hydrogels have been developed as bioactive matrices, promoting wound healing and tissue repair through external cellular stimulation. Among various therapeutic inorganic ions, zinc ions (Zn²⁺), in particular, play essential roles in wound healing by modulating cell proliferation and angiogenesis and facilitating tissue remodeling. Numerous strategies have been developed to fabricate Zn²⁺-releasing biomaterials; however, these methods often encounter challenges, including complex fabrication processes, rapid ion release, and limited mechanical stability. To address these challenges, we developed a novel Zn²⁺-releasing bioactive hydrogel (Zn-Gel) as a bioactive matrix that supported wound healing via a zinc peroxide (ZnO₂)-mediated cross-linking reaction. Zn-Gel was fabricated by combining thiolated gelatin with ZnO₂ solutions, forming a hydrogel with controllable Zn²⁺ release kinetics that depended on ZnO₂ concentration and enabled sustained release of Zn²⁺ for up to 14 d. Zn-Gel demonstrated excellent cytocompatibility and tissue compatibility in both in vitro and in vivo studies. Interestingly, Zn-Gel accelerated wound healing by promoting cell proliferation, blood vessel formation, hair follicle formation, and collagen deposition. Therefore, Zn-Gel holds great potential as an advanced bioactive material for wound healing and tissue regeneration.