Biomaterials最新文献_第10页

Design and characterization of in situ cell-penetrating multi-modal gadolinium-gold nanoparticles for MR and CT imaging 用于磁共振和CT成像的原位细胞穿透多模态钆-金纳米颗粒的设计和表征

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123947

Alena Kisel , Minrui Luo , Matthew D. Bailey , Kathryn Ghobrial , Luydmila Lukashova , Yiqing Lei , T. Kevin Hitchens , Thomas J. Meade , Michel Modo

Contrast agents capable of labeling cells in situ are essential for tracking individual cells as they migrate through tissues during dynamic biological processes. Gold nanoparticles (AuNPs) conjugated with gadolinium (Gd) and fluorochromes offer multimodal detection via magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence microscopy. In this study, a systematic strategy was employed to incrementally increase the complexity of Gd-labeled AuNPs (GdAuNPs) and evaluate four distinct surface chemistries for in situ cell labeling. Comprehensive characterization of GdAuNP synthesis and stability—using inductively coupled plasma mass spectrometry, UV/visible spectroscopy, transmission electron microscopy, and MR relaxometry—demonstrated high reproducibility and a long shelf-life. Following intracerebroventricular or intrastriatal injection, histological analyses revealed that GdAuNPs labeled over 80 % of neurons in the striatum and approximately 20 % of neural stem cells (NSCs) in the subventricular zone. Only GdAuNPs functionalized with single-stranded DNA (ssDNA) were efficiently internalized by cells; GdAuNPs lacking ssDNA remained extracellular and were removed during immunohistochemical processing. ssDNA-labeled GdAuNPs localized peri-nuclearly following endocytosis. In microglia, GdAuNP also accumulated near the nucleus, whereas in macrophages, all GdAuNP formulations—including those with ssDNA—were mostly sequestered within phagosomes, indicating uptake via phagocytosis. The most effective design, termed type D GdAuNP, featured Gd chelates conjugated both to ssDNA and directly to the AuNP surface. These nanoparticles exhibited the highest MR sensitivity and contrast-to-noise ratio in MRI after in situ labeling and were also robustly detected by μCT. This stepwise approach to nanoparticle optimization demonstrates the potential to enhance multimodal imaging sensitivity, supporting the feasibility of a noninvasive visualization of in situ labeled neurons and NSCs.

造影剂能够标记细胞在原位是必要的跟踪单个细胞，因为他们在动态的生物过程中通过组织迁移。金纳米颗粒（AuNPs）与钆（Gd）和荧光染料结合，通过磁共振成像（MRI）、计算机断层扫描（CT）和荧光显微镜提供多模态检测。在这项研究中，采用了一种系统的策略来逐步增加gd标记的AuNPs （GdAuNPs）的复杂性，并评估四种不同的表面化学物质用于原位细胞标记。综合表征GdAuNP合成和稳定性-使用电感耦合等离子体质谱，紫外/可见光谱，透射电子显微镜和磁共振弛豫测量-证明了高重复性和长保质期。在脑室内或纹状体内注射后，组织学分析显示GdAuNPs标记了纹状体中80%以上的神经元和约20%的脑室下区神经干细胞（NSCs）。只有被单链DNA功能化的GdAuNPs才能被细胞有效地内化；缺乏ssDNA的GdAuNPs留在细胞外，并在免疫组织化学处理过程中被去除。ssdna标记的GdAuNPs在胞吞作用后定位于核周围。在小胶质细胞中，GdAuNP也在细胞核附近积累，而在巨噬细胞中，所有GdAuNP配方（包括那些含有ssdna的配方）大多被隔离在吞噬体内，表明通过吞噬作用被摄取。最有效的设计称为D型GdAuNP，其特点是Gd螯合物既与ssDNA结合，又直接与AuNP表面结合。在原位标记后，这些纳米颗粒在MRI上表现出最高的MR灵敏度和对比噪声比，并且在μCT上也具有很强的检测能力。这种逐步优化纳米颗粒的方法证明了提高多模态成像灵敏度的潜力，支持了原位标记神经元和NSCs的无创可视化的可行性。

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引用次数: 0

ROS-triggered transformation of microgels to bioadhesive patch for orally administrated treatment of inflammatory bowel disease ros触发的微凝胶转化为生物粘接贴片用于炎症性肠病的口服治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123937

Yi-jing Yin , Kuo-ran Xing , Yu-tong Li , Fan Jia , Ting Ding , Min-jie Chen , Tian-tian Zhang , Jian Ji , Ke-feng Ren , Cheng-fu Xu , Jie Zhang

Inflammatory bowel diseases (IBD) are driven by excessive reactive oxygen species (ROS) and progressive disruption of the intestinal mucus barrier, yet sustained mucosal protection remains insufficiently addressed by current therapies. Here, we develop an orally administered, inflammation-activated microgel system (iPatch) that undergoes a ROS-triggered microgel-to-patch transformation specifically at inflamed intestinal sites. Unlike pre-formed hydrogels or enema-based formulations, this in situ transformation enables prolonged mucosal retention, adaptive barrier reconstruction, and sequential dual-drug release after oral dosing. In colitis mouse models, iPatch restores epithelial integrity, suppresses inflammation, and significantly improves clinical outcomes. This self-transforming oral patch system offers a patient-friendly and mechanistically distinct strategy for IBD treatment.

炎症性肠病（IBD）是由过多的活性氧（ROS）和肠道粘液屏障的进行性破坏驱动的，但目前的治疗方法仍然不足以解决持续的粘膜保护问题。在这里，我们开发了一种口服的炎症激活微凝胶系统（iPatch），它经历了ros触发的微凝胶到贴片的转化，特别是在炎症的肠道部位。与预先形成的水凝胶或灌肠制剂不同，这种原位转化能够延长粘膜保留时间，适应性屏障重建，并在口服给药后连续释放双药。在结肠炎小鼠模型中，ippatch可恢复上皮完整性，抑制炎症，并显著改善临床结果。这种自我转化的口腔贴片系统为IBD治疗提供了一种对患者友好且机制独特的策略。

引用次数: 0

Solvent-free melt-electrowriting of polycaprolactone-bioceramic composites 聚己内酯-生物陶瓷复合材料的无溶剂熔融电解。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123943

M.L. Eames , A. Weekes , T. Ayyachi , R.A. Pepper , E. Pickering , S. Bell , C. Wu , M.A. Woodruff , T.J. Klein

With increasing surgical cases for bone reconstruction, there is a rising need for advanced synthetic graft materials. In this paper, a novel pipeline for fabricating polycaprolactone (PCL)/bioceramic scaffolds was used to produce micron-fibre composite scaffolds comprising either 25 wt% 45S5 bioglass/45K PCL or 25 wt% molybdenum-doped bioglass/45K PCL (MoBG/PCL). Cryomixing was shown to be an effective method for evenly dispersing high concentrations of finely milled bioceramic particles into PCL without the need for chloroform solvents. The resulting composites had sufficiently low viscosity at 120 °C to be printed using melt electrowriting (MEW). The addition of bioceramic particles into PCL increased the elastic modulus and dramatically reduced the elongation at break. MEW scaffolds printed from a MoBG/PCL composite were shown to effectively support osteoblast cell growth. The cells on MoBG/PCL constructs displayed greater metabolic activity and DNA concentration after 7 days in culture relative to constructs made from unmodified PCL. Concentrated MoBG/PCL composite scaffolds may be a promising pathway for advanced bone tissue scaffolds.

随着骨重建手术病例的增加，对先进合成移植材料的需求也在不断增加。本文提出了一种新型制备聚己内酯/生物陶瓷支架的工艺流程，用于制备含有25% 45S5生物玻璃/45K PCL或25%掺钼生物玻璃/45K PCL （MoBG/PCL）的微米纤维复合支架。低温混合被证明是一种有效的方法均匀分散高浓度的精细研磨的生物陶瓷颗粒到PCL而不需要氯仿溶剂。所得到的复合材料在120°C下具有足够低的粘度，可以使用熔体电解（MEW）进行印刷。生物陶瓷颗粒的加入提高了PCL的弹性模量，并显著降低了断裂伸长率。由MoBG/PCL复合材料打印的新骨支架可以有效地支持成骨细胞的生长。与未经修饰的PCL构建物相比，MoBG/PCL构建物上的细胞在培养7天后显示出更高的代谢活性和DNA浓度。高浓度MoBG/PCL复合支架可能是高级骨组织支架的一个有前途的途径。

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引用次数: 0

Long-acting multiple programmed cell death nanoinducers based on polyunsaturated fatty acid supplemented liposomal photosensitizers for enhanced photodynamic immunotherapy 基于多不饱和脂肪酸补充脂质体光敏剂增强光动力免疫治疗的长效多重程序性细胞死亡纳米诱导剂

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123948

Yu Hao , Minming Chen , Yunyun Zhang , Hongchao Yang , Sisi Ling , Chunjie Wang , Yujie Zhu , Ziliang Dong , Chunyan Li , Zhuang Liu , Liangzhu Feng

Photodynamic therapy (PDT) has been investigated for minimal invasive treatment of superficial tumors, but its clinical efficacy is constrained by its immediate light-dependent cytotoxicity, low immunogenicity, and other reasons. Building on the capacity of polyunsaturated fatty acids (PUFAs) to convert short-lived reactive oxygen species into longer-lived, highly cytotoxic lipid radicals, we develop a long-acting liposomal photosensitizer by co-encapsulating chlorin e6 (Ce6) and linoleic acid (LA) with commercial lipids. The resulting LA-Ce6@liposome converts short-lived singlet oxygens to persistent lipid radicals during light exposure, sustaining free LA peroxidation even post-irradiation. Mechanistic studies demonstrate that LA-Ce6@liposome-mediated PDT drives immunogenic ferroptosis and PANoptosis in cancer cells via amplified lipid peroxidation. In preclinical models, this strategy not only inhibits the growth of light-irradiated primary tumors but also activates systemic antitumor immunity, delaying progression of distal metastatic and rechallenged tumors, particularly when synergized with immune checkpoint blockade therapy. This study highlights a streamlined strategy to augment conventional PDT by integrating photosensitizers with PUFAs, offering prolonged tumoradical activity and immune activation.

光动力疗法（PDT）已被研究用于浅表肿瘤的微创治疗，但其临床疗效受到其直接的光依赖性细胞毒性、低免疫原性等原因的限制。基于多不饱和脂肪酸（PUFAs）将短寿命活性氧转化为长寿命、高细胞毒性的脂质自由基的能力，我们开发了一种长效脂质体光敏剂，通过将氯e6 （Ce6）和亚油酸（LA）与商业脂质共包封。由此产生的LA-Ce6@liposome在光照下将短寿命的单线态氧转化为持久的脂质自由基，即使在照射后也能维持自由的LA过氧化。机制研究表明LA-Ce6@liposome-mediated PDT通过放大脂质过氧化作用驱动癌细胞免疫原性铁下垂和PANoptosis。在临床前模型中，该策略不仅可以抑制光照射原发肿瘤的生长，还可以激活全身抗肿瘤免疫，延缓远端转移和再挑战肿瘤的进展，特别是当与免疫检查点阻断疗法协同时。本研究强调了一种简化的策略，通过将光敏剂与pufa结合来增强传统的PDT，提供延长的肿瘤活性和免疫激活。

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引用次数: 0

Targeting hypersialylation via lectin-directed protein aggregation therapy (LPAT) for anti-metastasis applications 通过凝集素定向蛋白聚集疗法（LPAT）靶向高唾液化用于抗转移应用

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-23 DOI: 10.1016/j.biomaterials.2025.123945

Xiao Han , Yifei Liu , Jingjin Zhou , Ka Lun Lai , Jianing Zhang , Yufei Li , Jyotsna Jai , Jinqing Huang , Henry Lam , Kenward Vong

Here, we report the development of lectin-directed protein aggregation therapy (LPAT), which combines the strong glycan-targeting capabilities of multivalent lectins with the aggregating propensities of bacterial microcompartment proteins. The design aims to create a system sensitive enough to elicit cell-specific aggregation towards invasive, metastatic tumor cells, while being nontoxic to normal tissues. LPAT agents were screened against a panel of 6 breast cancer cell lines, with the most potent agent showing preferential anti-adhesive and anti-invasive activity against the hypersialylated/MMP9 overexpressing MDA-MB-231 cell line. Furthermore, LPAT agents did not exhibit any propensity for hemagglutination, a principal disadvantage of lectin-based targeting systems. Subsequent studies using a metastatic mouse model showed that LPAT agents could prevent the formation of experimental lung metastases caused by the highly metastatic MDA-MB-231-LM2 isoform cell line. Overall, this work has laid the foundation for a potential glycan-targeting therapy aimed at preventing the onset and progression of metastatic tumors in a safe and selective manner.

在这里，我们报道了凝集素定向蛋白聚集疗法（LPAT）的发展，它结合了多价凝集素强大的聚糖靶向能力和细菌微室蛋白的聚集倾向。该设计旨在创建一个足够敏感的系统，以诱导细胞特异性聚集到侵袭性、转移性肿瘤细胞，同时对正常组织无毒。LPAT药物对6种乳腺癌细胞系进行了筛选，最有效的药物对高唾液化/MMP9过表达的MDA-MB-231细胞系显示出优先的抗粘附和抗侵袭活性。此外，LPAT制剂没有表现出任何血凝倾向，这是基于凝集素的靶向系统的主要缺点。随后使用转移小鼠模型进行的研究表明，LPAT药物可以阻止高转移性MDA-MB-231-LM2亚型细胞系引起的实验性肺转移的形成。总的来说，这项工作为潜在的靶向治疗奠定了基础，旨在以安全和选择性的方式预防转移性肿瘤的发生和进展。

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引用次数: 0

Engineering fluorescent iNOS-Inhibitory covalent organic frameworks: Fewer doses than fluticasone propionate for house dust mite-induced allergic rhinitis treatment 工程荧光inos -抑制共价有机框架：比丙酸氟替卡松治疗屋尘螨引起的变应性鼻炎的剂量更少

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-23 DOI: 10.1016/j.biomaterials.2025.123946

Shu-Jia Sang , Jia-Lu Zhuang , Xi-Xi Chen , Wen-Long Huang , Zhong-Lian Wang , Ji Lu , Mao-Yu Jiang , Yu-Chen Liu , Qin Wang , Guiyang Zhang , Ye-Hai Liu

Allergic rhinitis (AR) is a chronic inflammatory disease primarily mediated by T_H2-type immune responses, which is clinically managed with glucocorticoid therapy. However, this approach is limited by its variable efficacy and notable side effects. Herein, we developed two covalent organic framework (COF) nanoflakes—Aming-COF and Aming-BCOF—with inducible nitric oxide synthase (iNOS) inhibitory functions. We achieved targeted delivery and in vivo tracing by polymerizing the iNOS inhibitor aminoguanidine with a tetraphenylethylene fluorescent group through covalent bonds. In a mouse AR model induced by house dust mites, intranasal administration of Aming-COF demonstrated therapeutic efficacy: inhibiting excessive iNOS expression in the nasal mucosa to alleviate oxidative stress damage; repairing tight junction proteins such as ZO-1 and occludin to enhance epithelial barrier function; and regulating GATA-3/T-bet expression to rebalance T_H1/T_H2 immunity, thereby reducing T_H2-type cytokines such as IL-4 and IL-5 while increasing T_H1-type IFN-γ levels. Transcriptome analysis revealed its mechanism of action: inhibition of the IL5Rα-JAK-STAT signaling pathway. Aming-COF showed greater efficacy than fluticasone propionate with fewer doses (3 vs. 5) and no significant hepatotoxicity or nephrotoxicity, indicating good biosafety. This study provides a novel nanomaterial strategy for AR precision therapy and opens new directions for the application of COFs in immune regulation.

变应性鼻炎（AR）是一种主要由th2型免疫反应介导的慢性炎症性疾病，临床上主要采用糖皮质激素治疗。然而，这种方法因其疗效不一和明显的副作用而受到限制。在此，我们开发了两种具有诱导型一氧化氮合酶（iNOS）抑制功能的共价有机框架（COF）纳米片——aming -COF和aming - bcof。我们通过共价键将iNOS抑制剂氨基胍与四苯基荧光基团聚合，实现了靶向递送和体内追踪。在室内尘螨诱导的小鼠AR模型中，经鼻给药阿明- cof显示出治疗效果：抑制鼻黏膜iNOS过度表达，减轻氧化应激损伤；修复紧密连接蛋白如ZO-1和occludin，增强上皮屏障功能；调节GATA-3/T-bet表达，重新平衡TH1/TH2免疫，从而降低TH2型细胞因子如IL-4和IL-5，同时增加TH1型IFN-γ水平。转录组分析揭示其作用机制：抑制IL5Rα-JAK-STAT信号通路。阿明- cof比丙酸氟替卡松更有效，且剂量更少（3比5），无明显肝毒性或肾毒性，表明生物安全性良好。本研究为AR精准治疗提供了一种新的纳米材料策略，为COFs在免疫调节中的应用开辟了新的方向。

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引用次数: 0

Multifunctional hollow manganese silicate nanoparticles for the treatment of acute lung injury and Pseudomonas aeruginosa pulmonary infection 多功能中空硅酸锰纳米颗粒治疗急性肺损伤和铜绿假单胞菌肺部感染

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-23 DOI: 10.1016/j.biomaterials.2025.123944

Jingge Ma , Lin Du , Xiyue Shen , Jiayi Wang , Hao Qian , Chengtie Wu , Jin-Fu Xu

Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition associated with high morbidity and mortality, underscoring the urgent need for effective treatment options. This study proposes a nanotherapeutic strategy for acute lung injury (ALI) based on manganese silicate (MS) hollow nanospheres, whose intrinsic properties include ROS scavenging enabled by multivalent Mn, and immunomodulatory and tissue-protective effects endowed by the bioactive ions released from MS. The designed hollow structure of MS grants the nanoparticles with drug delivery capability. Taking advantage of multiple bioactivities, MS nanospheres suppress inflammation, reduce oxidative stress, and support the recovery of the alveolar-capillary barrier in the lipopolysaccharide (LPS)-induced acute lung injury model. Furthermore, following the utilization as a drug delivery vehicle, MS nanospheres effectively target Pseudomonas aeruginosa-induced acute pulmonary infection, achieving synergistic effects between the intrinsic bioactivity and antimicrobial therapy. Therefore, the study presents a versatile nanoplatform with a combination of anti-inflammatory, antioxidant, and injury-mitigating biofunctions, offering a promising strategy of nanomedicine application for the management of inflammatory lung diseases.

急性呼吸窘迫综合征（ARDS）是一种与高发病率和死亡率相关的严重炎症性肺部疾病，迫切需要有效的治疗方案。本研究提出了一种基于硅酸锰（MS）空心纳米球的急性肺损伤（ALI）纳米治疗策略，其内在特性包括多价锰的活性氧清除作用，以及MS释放的生物活性离子赋予的免疫调节和组织保护作用。在脂多糖（LPS）诱导的急性肺损伤模型中，MS纳米微球利用多种生物活性，抑制炎症，减少氧化应激，支持肺泡-毛细血管屏障的恢复。此外，作为药物递送载体，质谱纳米球可以有效靶向铜绿假单胞菌诱导的急性肺部感染，实现内在生物活性和抗菌治疗的协同效应。因此，该研究提出了一种具有抗炎、抗氧化和减轻损伤生物功能的多功能纳米平台，为纳米医学应用于炎症性肺部疾病的治疗提供了一种有前景的策略。

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引用次数: 0

Thrombogenic characterization of alloyed and surface-modified magnesium bioresorbable metals for cardiovascular device applications 用于心血管装置的合金和表面改性镁生物可吸收金属的血栓形成特性

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-22 DOI: 10.1016/j.biomaterials.2025.123935

Cole A. Baker, Jennifer J. Johnson, Monica T. Hinds, Deirdre E.J. Anderson

Magnesium alloys show great promise for use in bioresorbable metal vascular stents due to their mechanical properties. However, considerable material engineering efforts are required to reduce the corrosion rate of magnesium and translate these stents into clinical use. Alloying elements and surface modifications are frequently used to reduce corrosion rate and retain mechanical strength for a longer time. This work sought to characterize the effects that these alloying approaches and surface modifications have on the acute thrombogenicity of magnesium scaffolds. Common magnesium alloys were assessed in conjunction with a biostable clinical control in both ex vivo whole blood and in vitro assays. Our results indicated that magnesium alloying did not affect the thrombogenicity of the material with equivalent platelet deposition and fibrin accumulation on all of the alloyed magnesium metals, as well as in the alloys’ proclivity to produce fibrin or activate factor XII (FXII). In contrast, surface modifications of magnesium, specifically fluorination and anodization, increased platelet deposition and fibrin accumulation onto the magnesium surface compared to the unmodified metal. No differences were found in fibrin or FXIIa generation between surface-modified and the unmodified magnesium material. In conclusion, this research demonstrated that alloying is a viable strategy to increase magnesium corrosion resistance without affecting its thrombogenicity, whereas surface modifications to magnesium may increase the material thrombogenicity.

镁合金具有良好的机械性能，在生物可吸收金属血管支架中具有广阔的应用前景。然而，需要大量的材料工程努力来降低镁的腐蚀速度并将这些支架转化为临床应用。合金元素和表面改性经常用于降低腐蚀速率和保持机械强度更长时间。这项工作旨在表征这些合金化方法和表面修饰对镁支架的急性血栓形成性的影响。普通镁合金在离体全血和体外试验中与生物稳定性临床对照一起进行了评估。我们的研究结果表明，镁合金不会影响材料的血栓形成性，在所有合金镁金属上都有相当的血小板沉积和纤维蛋白积累，也不会影响合金产生纤维蛋白或激活因子XII （FXII）的倾向。相比之下，镁的表面修饰，特别是氟化和阳极氧化，与未修饰的金属相比，增加了镁表面的血小板沉积和纤维蛋白积累。表面修饰的镁材料与未修饰的镁材料在纤维蛋白和FXIIa生成方面没有差异。总之，本研究表明合金化是一种可行的策略，可以提高镁的耐腐蚀性而不影响其血栓性，而对镁进行表面改性可能会增加材料的血栓性。

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引用次数: 0

Glycolysis inhibition-based breakdown of ferroptosis defenses to achieve ferroptosis and immune cascades for antitumor therapy 以糖酵解抑制为基础，破坏铁下垂防御，实现铁下垂和免疫级联，用于抗肿瘤治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-22 DOI: 10.1016/j.biomaterials.2025.123939

Nan Liu , Xiangling Ren , Hening Zhuang , Shimei Li , Zengzhen Chen , Longfei Tan , Changhui Fu , Qiong Wu , Yongxiang Zhao , Xianwei Meng

As a newly identified type of regulated cell death, ferroptosis has attracted considerable attention within cancer treatment research. Nevertheless, tumor cells often evade ferroptosis through defensive mechanisms such as aberrant energy metabolism and elevated glutathione (GSH) levels, which help maintain intracellular redox homeostasis. The potential of targeting energy metabolism to disrupt ferroptosis resistance in cancer treatment has been largely overlooked. In this study, we constructed a purposefully engineered nanoplatform utilizing a hollow metal–organic framework as its foundation (ZIF-90), denoted as ZIF-90-ruthenium (Ru)-Apigenin@Tetradecanol-PEG (ZRATP), to disrupt redox balance and establish a tumor microenvironment (TME) conducive to ferroptosis via glycolysis inhibition. Under simultaneous microwave irradiation and acidic TME conditions, ZRATP gradually releases apigenin and Ru. Apigenin acts as a glycolysis inhibitor by targeting pyruvate kinase M2, thereby reprogramming tumor metabolism to favor ferroptosis. Concurrently, Ru depletes GSH and generates reactive oxygen species, directly disturbing redox homeostasis and initiating ferroptosis. This ferroptotic process not only induces immunogenic cell death but also recruits damage-associated molecular patterns. Glycolysis inhibition further alleviates the immunosuppressive TME and enhances immune cell infiltration. These activated immune cells secrete interferon-γ, which downregulates the cystine/glutamate antiporter (system Xc-), thereby further promoting ferroptosis. Together, these effects establish a self-amplifying cycle where metabolic intervention and immune activation synergistically enhance ferroptosis in tumor cells. ZRATP represents a novel strategic platform for the treatment of malignant tumors.

作为一种新发现的受调控细胞死亡类型，铁下垂在癌症治疗研究中引起了相当大的关注。然而，肿瘤细胞通常通过异常的能量代谢和谷胱甘肽（GSH）水平升高等防御机制来逃避铁凋亡，这有助于维持细胞内氧化还原稳态。在癌症治疗中，靶向能量代谢破坏铁下垂抵抗的潜力在很大程度上被忽视了。在这项研究中，我们构建了一个有目的的工程纳米平台，以中空金属有机框架（ZIF-90）为基础，标记为ZIF-90-钌(Ru)-Apigenin@Tetradecanol-PEG (ZRATP)，通过糖酵解抑制来破坏氧化还原平衡，建立一个有利于铁死亡的肿瘤微环境（TME）。在微波辐照和酸性TME条件下，ZRATP逐渐释放出芹菜素和Ru。芹菜素作为糖酵解抑制剂，靶向丙酮酸激酶M2，从而重编程肿瘤代谢，有利于铁下垂。同时，Ru消耗谷胱甘肽并产生活性氧，直接扰乱氧化还原稳态并启动铁死亡。这一过程不仅诱导免疫原性细胞死亡，而且还招募损伤相关的分子模式。糖酵解抑制进一步减轻免疫抑制性TME，增强免疫细胞浸润。这些被激活的免疫细胞分泌干扰素-γ，其下调胱氨酸/谷氨酸反转运蛋白（系统Xc-），从而进一步促进铁下垂。总之，这些效应建立了一个自我放大的循环，代谢干预和免疫激活协同增强肿瘤细胞的铁下垂。ZRATP为恶性肿瘤的治疗提供了新的战略平台。

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引用次数: 0

Dynamic stimulation of piezoelectric scaffolds enhances osteogenesis-related biological responses via electro-mechanical sensitive channels and cytoskeletal remodeling 压电支架的动态刺激通过机电敏感通道和细胞骨架重塑增强成骨相关的生物反应

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-22 DOI: 10.1016/j.biomaterials.2025.123938

Ju Liu , Xinyu Wang , Zhifeng Wu , Zongjie Hui , Jun Zhang , Jiawen Zhang , Xianbo Qiu , Sailing He , Yingjie Yu , Xiaoping Yang , Qing Cai

The inherent electrophysiological properties of natural bone tissue and the enhancement of bone healing via endogenous electric field highlight the importance of piezoelectric biomaterials for neovascularized bone regeneration. However, current research predominantly utilizes static conditions for in vitro cell studies and relies largely on non-load-bearing calvarial defect models for animal evaluations. To investigate how piezoelectric scaffolds influence cell behaviors under dynamic mechanical stimulation, this study employs a custom-made circulating compression system to perform dynamic cell culture experiments on a piezoelectric cryogel scaffold. The scaffold consists of methacrylated gelatin (GelMA) combined with piezoelectric whitlockite (PWH), exhibiting outstanding shape deformation-recovery stability under cyclic mechanical loading. Mechanical stimulation was applied at two distinct frequencies (1 Hz and 2 Hz) to simulate conditions similar to walking and jogging. Bone marrow mesenchymal stromal cells (BMSCs) seeded onto the scaffold were assessed for their potential to undergo osteogenic, angiogenic, and neurogenic differentiation in response to dynamic mechanical stimuli. Notably, the electrical signals generated by the scaffold significantly influence BMSCs proliferation and differentiation. These effects are mediated through mechanisms including activation of ionic channels, enhanced influx of Ca²⁺/Mg²⁺ ions, cytoskeletal remodeling, and actomyosin contractility. This study provides clear evidences linking scaffold piezoelectricity with specific cellular responses essential for osteogenesis and bone regeneration. Overall, the findings offer valuable insights into the roles of electroactive biomaterials in tissue repair, guiding future development of advanced scaffolds for bone tissue engineering.

天然骨组织固有的电生理特性和内源性电场对骨愈合的促进作用凸显了压电生物材料在新生血管骨再生中的重要性。然而，目前的研究主要利用静态条件进行体外细胞研究，并在很大程度上依赖于非承重颅骨缺损模型进行动物评估。为了研究压电支架在动态力学刺激下对细胞行为的影响，本研究采用定制的循环压缩系统在压电低温凝胶支架上进行了动态细胞培养实验。该支架由甲基丙烯酸明胶（GelMA）与压电whitlockite （PWH）结合而成，在循环机械载荷下表现出出色的形状变形-恢复稳定性。机械刺激应用于两个不同的频率（1hz和2hz）来模拟类似于步行和慢跑的情况。将骨髓间充质基质细胞（BMSCs）植入支架，评估其在动态机械刺激下发生成骨、血管生成和神经生成分化的潜力。值得注意的是，支架产生的电信号显著影响骨髓间充质干细胞的增殖和分化。这些作用是通过离子通道激活、Ca2+/Mg2+离子内流增强、细胞骨架重塑和肌动球蛋白收缩等机制介导的。这项研究提供了明确的证据，表明支架压电性与骨生成和骨再生所必需的特定细胞反应有关。总的来说，这些发现为电活性生物材料在组织修复中的作用提供了有价值的见解，指导了未来骨组织工程先进支架的发展。

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