Bioactive Materials最新文献_第3页

The anti-oxidation related bioactive materials for intervertebral disc degeneration regeneration and repair 用于椎间盘退变再生和修复的抗氧化相关生物活性材料

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-09 DOI: 10.1016/j.bioactmat.2024.10.012

Yingjie Mai , Siying Wu , Penghui Zhang , Ningning Chen , Jun Wu , Fuxin Wei

Intervertebral disc degeneration (IVDD) is a prevalent chronic spinal condition characterized by the deterioration of the intervertebral discs (IVD), leading to structural damage and associated pain. This degenerative process is closely linked to oxidative stress injury, which plays a pivotal role in its onset and progression. Oxidative stress in IVDD results from the excessive production of reactive oxygen species (ROS) and impaired ROS clearance mechanisms, disrupting the redox balance within the intervertebral disc. Consequently, oxidative stress contributes to the degradation of the extracellular matrix (ECM), promotes cell apoptosis, and exacerbates disc tissue damage. Current treatment options for IVDD face significant challenges in effectively alleviating the oxidative stress-induced damage and facilitating disc tissue repair. However, recent advancements in biomaterials have opened new avenues of hope for IVDD treatment by addressing oxidative stress. In this review, we first provide an overview of the pathophysiological process of IVDD and explore the mechanisms and pathways associated with oxidative stress injury. Then, we delve into the current research on antioxidant biomaterials employed in the treatment of IVDD, and outline the advantages and limitations of hydrogel, nanomaterials, polyphenol and inorganic materials. Finally, we propose the future research direction of antioxidant biomaterials in IVDD treatment. The main idea of this review is shown in Scheme 1.

椎间盘变性（IVDD）是一种普遍存在的慢性脊柱疾病，其特点是椎间盘（IVD）退化，导致结构性损伤和相关疼痛。这种退化过程与氧化应激损伤密切相关，氧化应激损伤在其发生和发展过程中起着关键作用。IVDD 中的氧化应激源于活性氧（ROS）的过度产生和 ROS 清除机制的受损，从而破坏了椎间盘内的氧化还原平衡。因此，氧化应激会导致细胞外基质（ECM）降解，促进细胞凋亡，加剧椎间盘组织损伤。目前的 IVDD 治疗方案在有效缓解氧化应激引起的损伤和促进椎间盘组织修复方面面临巨大挑战。然而，生物材料的最新进展为通过解决氧化应激问题治疗 IVDD 带来了新的希望。在本综述中，我们首先概述了 IVDD 的病理生理过程，并探讨了与氧化应激损伤相关的机制和途径。然后，我们深入探讨了目前用于治疗 IVDD 的抗氧化生物材料的研究，概述了水凝胶、纳米材料、多酚和无机材料的优势和局限性。最后，我们提出了抗氧化生物材料在 IVDD 治疗中的未来研究方向。本综述的主要思路如方案 1 所示。

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引用次数: 0

Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair 通过免疫调节微球架起免疫-神经血管串扰的桥梁，促进神经修复

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-08 DOI: 10.1016/j.bioactmat.2024.10.031

Tongtong Xu , Lin Gan , Wei Chen , Dandan Zheng , Hanlai Li , Shiyu Deng , Dongliang Qian , Tingting Gu , Qianyuan Lian , Gracie Shen , Qingzhu An , Wanlu Li , Zhijun Zhang , Guo-Yuan Yang , Huitong Ruan , Wenguo Cui , Yaohui Tang

The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system (CNS) injury. Maintaining brain immune homeostasis is crucial for restoring neurovascular function. In this study, an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit, thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery. This immunomodulatory crosstalk microsphere (MP/RIL4) was composed of microglia-targeted RAP12 peptide-modified interleukin-4 (IL-4) nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques. We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β, iNOS, and CD86, while upregulating levels of anti-inflammatory factors such as IL-10, Arg-1, and CD206 in microglia. In addition, injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke, promoted neurobehavioral recovery, and enhanced the crosstalk between immune cells and the neurovascular unit, thus increasing angiogenesis and neurogenesis of stroke mice. In summary, the immunomodulatory microspheres, capable of orchestrating the interaction between immune cells and neurovascular unit, hold considerable therapeutic potential for ischemic stroke and other CNS diseases.

免疫细胞和神经血管单元之间的相互影响在中枢神经系统（CNS）损伤后的神经再生中起着关键作用。维持脑部免疫平衡对恢复神经血管功能至关重要。本研究通过免疫调节水凝胶微球开发了一种互动桥梁，将小胶质细胞和神经血管单元之间的互动网络连接起来，从而精确调节免疫-神经血管串扰，实现神经功能恢复。这种免疫调节串联微球（MP/RIL4）由小胶质细胞靶向 RAP12 肽修饰的白细胞介素-4（IL-4）纳米颗粒和硼酸酯功能化水凝胶组成，采用了生物素-avidin 反应和空气微流体技术。我们证实，免疫调节微球降低了小胶质细胞中IL-1β、iNOS和CD86等促炎因子的表达，同时上调了IL-10、Arg-1和CD206等抗炎因子的水平。此外，注射 MP/RIL4 还能显著减轻缺血性中风小鼠模型的脑萎缩体积，促进神经行为的恢复，并增强免疫细胞与神经血管单元之间的串联，从而增加中风小鼠的血管生成和神经再生。总之，免疫调节微球能够协调免疫细胞和神经血管之间的相互作用，对缺血性中风和其他中枢神经系统疾病具有相当大的治疗潜力。

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引用次数: 0

Emerging biotechnologies for engineering liver organoids 用于肝脏器官组织工程的新兴生物技术

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-08 DOI: 10.1016/j.bioactmat.2024.11.002

Junqi Zhao , Yue Zhi , Haozhen Ren , Jinglin Wang , Yuanjin Zhao

The engineering construction of the liver has attracted enormous attention. Organoids, as emerging miniature three-dimensional cultivation units, hold significant potential in the biomimetic simulation of liver structure and function. Despite notable successes, organoids still face limitations such as high variability and low maturity. To overcome these challenges, engineering strategies have been established to maintain organoid stability and enhance their efficacy, laying the groundwork for the development of advanced liver organoids. The present review comprehensively summarizes the construction of engineered liver organoids and their prospective applications in biomedicine. Initially, we briefly present the latest research progress on matrix materials that maintain the three-dimensional morphology of organoids. Next, we discuss the manipulative role of engineering technologies in organoid assembly. Additionally, we outline the impact of gene-level regulation on organoid growth and development. Further, we introduce the applications of liver organoids in disease modeling, drug screening and regenerative medicine. Lastly, we overview the current obstacles and forward-looking perspectives on the future of engineered liver organoids. We anticipate that ongoing innovations in engineered liver organoids will lead to significant advancements in medical applications.

肝脏的工程构造引起了极大的关注。有机体作为新兴的微型三维培养单元，在肝脏结构和功能的生物仿真模拟方面具有巨大潜力。尽管取得了显著的成功，但器官组织仍然面临着变异性大和成熟度低等限制。为了克服这些挑战，人们建立了工程策略来保持类器官的稳定性并提高其功效，从而为开发先进的肝脏类器官奠定了基础。本综述全面总结了工程肝脏器官组织的构建及其在生物医学中的应用前景。首先，我们简要介绍了保持器官组织三维形态的基质材料的最新研究进展。接着，我们讨论了工程技术在类器官组装中的操纵作用。此外，我们还概述了基因水平调控对类器官生长和发育的影响。此外，我们还介绍了肝脏类器官在疾病建模、药物筛选和再生医学中的应用。最后，我们概述了工程肝脏器官组织目前面临的障碍和对未来的前瞻性展望。我们预计，工程肝脏器官组织的不断创新将为医学应用带来重大进展。

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引用次数: 0

β-Ketoenamine covalent organic framework nanoplatform combined with immune checkpoint blockade via photodynamic immunotherapy inhibit glioblastoma progression β-酮胺共价有机框架纳米平台结合光动力免疫疗法的免疫检查点阻断抑制胶质母细胞瘤进展

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-07 DOI: 10.1016/j.bioactmat.2024.10.029

Tengfeng Yan , Qiuye Liao , Zhihao Chen , Yang Xu , Wenping Zhu , Ping Hu , Si Zhang , Yanze Wu , Lei Shu , Junzhe Liu , Min Luo , Hongxin Shu , Yilei Sheng , Li Wang , Chun Xu , Chang Lei , Hongming Wang , Qingsong Ye , Li Yang , Xingen Zhu

The synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma (GBM) patients. The observed upregulation of O-GlcNAc glycolysis in tumors may contribute to the stabilization of endogenous PD-L1 protein, facilitating tumor immune evasion. This study presents a pH-adapted excited state intramolecular proton transfer (ESIPT)-isomerized β-ketoamide-based covalent organic framework (COF) nanoplatform (denoted as OT@COF-RVG). Temozolomide (TMZ) and OSMI-4 (O-GlcNAc transferase inhibitor) were integrated into COF cavities, then modified on the surface with polyethylene glycol and the rabies virus peptide RVG-29, showing potential for sensitizing TMZ chemotherapy and initiating photodynamic therapy (PDT). By inhibiting O-GlcNAc and promoting lysosomal degradation of PD-L1, OT@COF-RVG enhanced the effectiveness of immune checkpoint blockade (ICB) therapy. Additionally, treatment with OT@COF-RVG led to a notable elevation in reactive oxygen species (ROS) levels, thereby re-establishing an immunostimulatory state, inducing immunogenic cell death (ICD). In summary, our research unveiled a correlation between O-GlcNAc in GBM and the evasion of immune responses by tumors, while showcasing the potential of OT@COF-RVG in reshaping the immunosuppressive microenvironment of GBM and offering a more effective approach to immunotherapy in clinical settings.

光动力免疫疗法与内源性清除PD-L1免疫检查点阻断疗法相结合的协同方法有望提高胶质母细胞瘤（GBM）患者的生存率。在肿瘤中观察到的O-GlcNAc糖酵解上调可能有助于稳定内源性PD-L1蛋白，从而促进肿瘤免疫逃避。本研究提出了一种与 pH 值相适应的激发态分子内质子转移（ESIPT）异构化β-酮酰胺基共价有机框架（COF）纳米平台（简称 OT@COF-RVG）。将替莫唑胺（TMZ）和OSMI-4（O-GlcNAc转移酶抑制剂）整合到COF空腔中，然后用聚乙二醇和狂犬病毒肽RVG-29对其表面进行修饰，显示了TMZ化疗增敏和启动光动力疗法（PDT）的潜力。通过抑制 O-GlcNAc 和促进 PD-L1 的溶酶体降解，OT@COF-RVG 增强了免疫检查点阻断疗法（ICB）的效果。此外，用 OT@COF-RVG 治疗会导致活性氧（ROS）水平显著升高，从而重建免疫刺激状态，诱导免疫原性细胞死亡（ICD）。总之，我们的研究揭示了 GBM 中的 O-GlcNAc 与肿瘤逃避免疫反应之间的相关性，同时展示了 OT@COF-RVG 在重塑 GBM 免疫抑制微环境方面的潜力，并为临床免疫疗法提供了一种更有效的方法。

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引用次数: 0

Conductive polyphenol microneedles coupled with electroacupuncture to accelerate wound healing and alleviate depressive-like behaviors in diabetes 导电多酚微针与电针相结合，加速伤口愈合并缓解糖尿病患者的抑郁样行为

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-07 DOI: 10.1016/j.bioactmat.2024.11.001

Yue Hou , Xiaochuan Guo , Jinhui Ran , Xiong Lu , Chaoming Xie

Inflammation and depression are serious complications of diabetes that interact to form a feedback loop and may hinder diabetic wound healing. They share a common pathophysiological basis of abnormal interactions between diabetic wounds and the brain. Here, we propose a strategy combining electroacupuncture (EA) stimulation of the Dazhui acupoint (GV14) with polyphenol-mediated conductive hydrogel microneedles to promote diabetic wound healing and alleviate depression through local wound–brain interactions. The conductive microneedles comprised methacrylated gelatin, dopamine (DA), DA-modified poly(3,4-ethylenedioxythiophene), and Lycium barbarum polysaccharide. EA at GV14 activated the vagus–adrenal axis to inhibit systemic inflammation while DA coupled electrical signals for long-term inhibition of local wound inflammation. EA at GV14 was also found to elevate 5-hydroxytryptamine levels in rats with diabetic wounds, consequently mitigating depressive-like behaviors. Additionally, the polyphenol-mediated conductive hydrogel microneedles, and coupled with EA stimulation promoted healing of wound tissue and peripheral nerves. This strategy regulated both local and systemic inflammation while alleviating depressive-like behaviors in diabetic rats, providing a new clinical perspective for the treatment of diabetes-related and emotional disorders.

炎症和抑郁是糖尿病的严重并发症，它们相互作用形成反馈回路，可能阻碍糖尿病伤口的愈合。它们有一个共同的病理生理基础，即糖尿病伤口与大脑之间的异常互动。在此，我们提出了一种策略，将刺激大椎穴（GV14）的电针（EA）与多酚介导的导电水凝胶微针相结合，通过局部伤口与大脑之间的相互作用促进糖尿病伤口愈合并缓解抑郁。导电微针由甲基丙烯酸明胶、多巴胺（DA）、DA 改性聚（3,4-亚乙二氧基噻吩）和枸杞多糖组成。龙胆紫 14 的 EA 可激活迷走神经-肾上腺轴，抑制全身炎症，而 DA 则可耦合电信号，长期抑制局部伤口发炎。研究还发现，GV14 的 EA 还能提高糖尿病伤口大鼠体内的 5- 羟色胺水平，从而减轻类似抑郁的行为。此外，多酚介导的导电水凝胶微针与 EA 刺激相结合，促进了伤口组织和外周神经的愈合。这种策略既能调节局部和全身炎症，又能减轻糖尿病大鼠的抑郁样行为，为治疗糖尿病相关疾病和情绪障碍提供了新的临床视角。

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引用次数: 0

Innovative spiral nerve conduits: Addressing nutrient transport and cellular activity for critical-sized nerve defects 创新性螺旋神经导管：解决临界尺寸神经缺损的营养运输和细胞活动问题

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-07 DOI: 10.1016/j.bioactmat.2024.10.028

Allen Zennifer , S.K. Praveenn Kumar , Shambhavi Bagewadi , Swathi Unnamalai , Davidraj Chellappan , Sama Abdulmalik , Xiaojun Yu , Swaminathan Sethuraman , Dhakshinamoorthy Sundaramurthi , Sangamesh G. Kumbar

Large-gap nerve defects require nerve guide conduits (NGCs) for complete regeneration and muscle innervation. Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration. Still, most are tubular with inadequate pore sizes and lack surface cues for nutrient transport, cell attachment, and tissue infiltration. This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane (TPU) fiber lattice. The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun aligned (aPHBV) and randomly (rPHBV) oriented nanofibers to enhance cellular activity. TPU lattices were made with 25 %, 35 %, and 50 % infill densities to create scaffolds with varied mechanical compliance. The fabricated TPU/PHBV spiral conduits had significantly higher surface areas (25 % TPU/PHBV: 698.97 mm², 35 % TPU/PHBV: 500.06 mm², 50 % TPU/PHBV: 327.61 mm²) compared to commercially available nerve conduits like Neurolac™ (205.26 mm²). Aligned PHBV nanofibers showed excellent Schwann cell (RSC96) adhesion, proliferation, and neurogenic gene expression for all infill densities. Spiral TPU/PHBV conduits with 25 % and 35 % infill densities exhibited Young's modulus values comparable to Neurotube® and ultimate tensile strength like acellular cadaveric human nerves. A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months, as evaluated by gait analysis, functional recovery, and histology. The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.

大间隙神经缺损需要神经引导导管（NGC）来实现完全再生和肌肉神经支配。为了促进轴突再生，人们利用各种支架设计和组织工程策略开发了许多 NGC。然而，大多数NGC都是管状的，孔隙大小不足，缺乏营养运输、细胞附着和组织浸润的表面线索。本研究利用 3D 打印热塑性聚氨酯（TPU）纤维晶格开发了一种多孔螺旋 NGC，以解决这些问题。为了增强细胞活性，该晶格用聚合（3-羟基丁酸-co-3-羟基戊酸）（PHBV）电纺排列（aPHBV）和随机（rPHBV）取向纳米纤维进行了功能化。TPU 网格的填充密度分别为 25%、35% 和 50%，以创建具有不同机械顺应性的支架。与 Neurolac™ 等市售神经导管（205.26 平方毫米）相比，制成的热塑性聚氨酯/PHBV 螺旋导管的表面积明显更高（25% 热塑性聚氨酯/PHBV：698.97 平方毫米；35% 热塑性聚氨酯/PHBV：500.06 平方毫米；50% 热塑性聚氨酯/PHBV：327.61 平方毫米）。排列整齐的 PHBV 纳米纤维在所有填充密度下都显示出出色的许旺细胞（RSC96）粘附、增殖和神经源基因表达能力。填充密度分别为 25% 和 35% 的螺旋形热塑性聚氨酯/PHBV 导管的杨氏模量值与 Neurotube® 不相上下，极限拉伸强度与无细胞尸体人类神经相当。通过步态分析、功能恢复和组织学评估，使用 TPU/aPHBV NGCs 治疗 Wistar 大鼠 10 毫米坐骨神经缺损 4 个月后，其肌肉神经支配和轴突愈合情况与自体移植相当。本研究中开发的 TPU/PHBV NGC 具有治疗大间隙神经缺损的前景。

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引用次数: 0

Nanoclay gels attenuate BMP2-associated inflammation and promote chondrogenesis to enhance BMP2-spinal fusion 纳米粘土凝胶可减轻 BMP2 相关炎症并促进软骨生成，从而增强 BMP2-脊髓融合能力

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-05 DOI: 10.1016/j.bioactmat.2024.10.027

Takuya Furuichi , Hiromasa Hirai , Takayuki Kitahara , Masayuki Bun , Masato Ikuta , Yuichiro Ukon , Masayuki Furuya , Richard O.C. Oreffo , Agnieszka A. Janeczek , Jonathan I. Dawson , Seiji Okada , Takashi Kaito

Bone morphogenetic protein 2 (BMP2) is clinically applied for treating intractable fractures and promoting spinal fusion because of its osteogenic potency. However, adverse effects following the release of supraphysiological doses of BMP2 from collagen carriers are widely reported. Nanoclay gel (NC) is attracting attention as a biomaterial, given the potential for localized efficacy of administered agents. However, the efficacy and mechanism of action of NC/BMP2 remain unclear. This study explored the efficacy of NC as a BMP2 carrier in bone regeneration and the enhancement mechanism. Subfascial implantation of NC containing BMP2 elicited superior bone formation compared with collagen sponge (CS). Cartilage was uniformly formed inside the NC, whereas CS formed cartilage only on the perimeter. Additionally, CS induced a dose-dependent inflammatory response around the implantation site, whereas NC induced a minor response, and inflammatory cells were observed inside the NC. In a rat spinal fusion model, NC promoted high-quality bony fusion compared to CS. In vitro, NC enhanced chondrogenic and osteogenic differentiation of hBMSCs and ATDC5 cells while inhibiting osteoclastogenesis. Overall, NC/BMP2 facilitates spatially controlled, high-quality endochondral bone formation without BMP2-induced inflammation and promotes high-density new bone, functioning as a next-generation BMP2 carrier.

骨形态发生蛋白 2（BMP2）具有成骨作用，因此被临床用于治疗难治性骨折和促进脊柱融合。然而，胶原蛋白载体释放超生理剂量的 BMP2 后产生不良反应的报道屡见不鲜。纳米粘土凝胶（NC）作为一种生物材料备受关注，因为它有可能使施用的药剂产生局部疗效。然而，NC/BMP2 的功效和作用机制仍不清楚。本研究探讨了 NC 作为 BMP2 载体在骨再生中的功效及其增强机制。与海绵胶原（CS）相比，筋膜下植入含有BMP2的NC能促进骨形成。软骨在 NC 内部均匀形成，而 CS 仅在周边形成软骨。此外，CS 会在植入部位周围诱发剂量依赖性炎症反应，而 NC 只诱发轻微反应，并且在 NC 内部也能观察到炎症细胞。在大鼠脊柱融合模型中，与CS相比，NC能促进高质量的骨融合。在体外，NC增强了hBMSCs和ATDC5细胞的软骨和成骨分化，同时抑制了破骨细胞的生成。总之，NC/BMP2 可促进空间可控的高质量软骨内骨形成，且不会引起 BMP2 诱导的炎症，还能促进高密度新骨的形成，可作为新一代 BMP2 载体发挥作用。

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引用次数: 0

Engineered nanoplatform mediated gas therapy enhanced ferroptosis for tumor therapy in vivo 工程纳米平台介导的气体疗法增强了体内治疗肿瘤的铁氧化作用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-05 DOI: 10.1016/j.bioactmat.2024.10.024

Kun Xu , Ke Li , Ye He , Yulan Mao , Xuan Li , Liangshuai Zhang , Meijun Tan , Yulu Yang , Zhong Luo , Peng Liu , Kaiyong Cai

The high glutathione (GSH) environment poses a significant challenge for inducing ferroptosis in tumor cells, necessitating the development of nanoplatforms that can deplete intracellular GSH. In this study, we developed an engineered nanoplatform (MIL-100@Era/L-Arg-HA) that enhances ferroptosis through gas therapy. First, we confirmed that the Fe element in the nanoplatform undergoes valence changes under the influence of high GSH and H₂O₂ in tumor cells. Meanwhile, L-Arg generates NO gas in the presence of intracellular H₂O₂, which reacts with GSH. Additionally, Erastin depletes GSH by inhibiting the cystine/glutamate antiporter system, reducing cystine uptake and impairing GPX4, while also increasing intracellular H₂O₂ levels by activating NOX4 protein expression. Through these combined GSH-depletion mechanisms, we demonstrated that MIL-100@Era/L-Arg-HA effectively depletes GSH levels, disrupts GPX4 function, and increases intracellular lipid ROS levels in vitro. Furthermore, this nanoplatform significantly inhibited tumor cell growth and extended the survival time of tumor-bearing mice in vivo. This engineered nanoplatform, which enhances ferroptosis through gas therapy, shows significant promise for ferroptosis-based cancer therapy and offers potential strategies for clinical tumor treatment.

高谷胱甘肽（GSH）环境对诱导肿瘤细胞铁突变构成了巨大挑战，因此有必要开发可消耗细胞内GSH的纳米平台。在这项研究中，我们开发了一种工程纳米平台（MIL-100@Era/L-Arg-HA），它能通过气体疗法增强铁突变。首先，我们证实了该纳米平台中的铁元素在肿瘤细胞的高GSH和H2O2影响下发生价态变化。同时，L-Arg 在细胞内 H2O2 的存在下生成 NO 气体，并与 GSH 发生反应。此外，Erastin 还通过抑制胱氨酸/谷氨酸抗转运体系统、减少胱氨酸摄取和损害 GPX4 来消耗 GSH，同时还通过激活 NOX4 蛋白表达来增加细胞内 H2O2 水平。通过这些联合的 GSH 消耗机制，我们证明 MIL-100@Era/L-Arg-HA 在体外有效地消耗了 GSH 水平，破坏了 GPX4 的功能，并增加了细胞内脂质 ROS 水平。此外，这种纳米平台还能明显抑制肿瘤细胞的生长，延长肿瘤小鼠的体内存活时间。这种通过气体疗法增强铁突变的工程纳米平台为基于铁突变的癌症疗法带来了巨大前景，并为临床肿瘤治疗提供了潜在策略。

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引用次数: 0

In vivo performance of lean bioabsorbable Mg–Ca alloy X0 and comparison to WE43: Influence of surface modification and alloying content 瘦生物可吸收镁钙合金 X0 的体内性能以及与 WE43 的比较：表面改性和合金含量的影响

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-05 DOI: 10.1016/j.bioactmat.2024.09.036

L. Berger , S. Dolert , T. Akhmetshina , J.-P. Burkhard , M. Tegelkamp , A.M. Rich , W. Rubin , S. Darwiche , G. Kuhn , R.E. Schäublin , B. von Rechenberg , B. Schaller , K.M. Nuss , J.F. Löffler

Magnesium alloys present a compelling prospect for absorbable implant materials in orthopedic and trauma surgery. This study evaluates an ultra-high purity, lean magnesium–calcium alloy (X0), both with and without plasma electrolytic oxidation (PEO) surface modification, in comparison to a clinically utilized WE43 magnesium alloy. It is shown that the mechanical properties of X0 can be tuned to yield a high-strength material suitable for bone screws (with an ultimate tensile strength of 336 MPa) or a ductile material appropriate for intraoperatively deformable plates (with an elongation at fracture of 24 %). Four plate-screw combinations were implanted onto the pelvic bones of six sheep without osteotomy for 8 weeks. Subsequent analysis utilized histology, micro-computed tomography, and light and electron microscopy. All implants exhibited signs of degradation and hydrogen-gas evolution, with PEO-coated X0 implants demonstrating the least volume loss and the most substantial new-bone formation on the implant surface and surrounding cancellous bone. Furthermore, the osteoconductive properties of the X0 implants, when uncoated, exceeded those of the uncoated WE43 implants, as evidenced by greater new-bone formation on the surface. This osteoconductivity was amplified with PEO surface modification, which mitigated gas evolution and enhanced osseointegration, encouraging bone apposition in the cancellous bone vicinity. These findings thus indicate that PEO-coated X0 implants hold substantial promise as a biocompatible and absorbable implant material.

镁合金是整形外科和创伤外科中一种前景广阔的可吸收植入材料。本研究评估了一种超高纯度、贫镁钙合金（X0），将其与临床上使用的 WE43 镁合金进行了比较，前者经过和未经过等离子电解氧化（PEO）表面改性。结果表明，X0 的机械性能可以进行调整，以获得适合骨螺钉的高强度材料（极限抗拉强度为 336 兆帕）或适合术中可变形钢板的韧性材料（断裂伸长率为 24%）。将四种钢板-螺钉组合植入六只绵羊的骨盆骨中，不进行截骨手术，为期八周。随后利用组织学、微型计算机断层扫描以及光镜和电子显微镜进行了分析。所有植入物都出现了降解和氢气演化的迹象，其中 PEO 涂层 X0 植入物的体积损失最小，植入物表面和周围松质骨的新骨形成最多。此外，X0 植入体在未涂层时的骨传导性能超过了未涂层的 WE43 植入体，其表面形成的新骨更多就证明了这一点。这种骨传导性在 PEO 表面改性后得到增强，PEO 可减轻气体演化，增强骨结合，促进松质骨附近的骨附着。因此，这些研究结果表明，PEO 涂层 X0 植入物作为一种生物相容性和可吸收性植入材料具有广阔的前景。

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引用次数: 0

Nucleotide coordinated polymers, a ROS-based immunomodulatory antimicrobial, doubly kill Pseudomonas aeruginosa biofilms of implant infections 核苷酸配位聚合物是一种基于 ROS 的免疫调节抗菌剂，可加倍杀死植入感染的铜绿假单胞菌生物膜

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-11-04 DOI: 10.1016/j.bioactmat.2024.10.026

Jinghuang Chen , Xianqing Tang , Qihan Sun , Xin Ji , Xingbo Wang , Zhendong Liu , Xu Zhang , Haijiao Xu , Fan Yang , Jian Sun , Xiurong Yang

Pseudomonas aeruginosa causes high morbidity and mortality in nosocomial infections, and newly approved antibiotics have been declining for decades. A green and universal deprotonation-driven strategy is used to screen the guanylic acid-metal ion coordination polymer nanoparticles (GMC), instead of the failure of binding occurs when specific metal ion participation. We find that the precise pH-dependent oxidase-like activity of GMC-2 orchestrates a duple symphony of immune modulation for Pseudomonas aeruginosa biofilm infections. Specifically, GMC-2-mediated reactive oxygen species (ROS) regulation triggers mitochondrial dysfunction and releases damage-associated molecular patterns, engaging pattern recognition receptors and resulting in endogenous innate immune activation. Meanwhile, GMC-2-triggered ROS generation in a mildly acidic biofilm environment destroys the biofilm, exposing exogenous pathogen-associated molecular patterns. GMC-2 cannot cause resistance for Pseudomonas aeruginosa compared with conventional antibiotics. In an infected implant mouse model, Pseudomonas aeruginosa biofilms were effectively eliminated by GMC-2-mediated triggering of innate and adaptive immunity. These findings provide a universal approach for facilitating the binding of biomolecules with metal ions and highlight the precise ROS-regulating platform plays a critical role in initiating endogenous and exogenous immune activation targeted for bacterial biofilm infection.

铜绿假单胞菌是导致高发病率和高死亡率的病原菌，几十年来新批准的抗生素一直在减少。我们采用了一种绿色、通用的去质子化驱动策略来筛选鸟苷酸-金属离子配位聚合物纳米粒子（GMC），而不是在特定金属离子参与时发生结合失败。我们发现，GMC-2 精确的 pH 依赖性氧化酶样活性为铜绿假单胞菌生物膜感染的免疫调节谱写了一曲双交响乐。具体来说，GMC-2 介导的活性氧（ROS）调节会引发线粒体功能障碍，并释放与损伤相关的分子模式，与模式识别受体结合，导致内源性先天性免疫激活。同时，在微酸性生物膜环境中，GMC-2 触发的 ROS 生成会破坏生物膜，暴露出外源性病原体相关分子模式。与传统抗生素相比，GMC-2 不会导致铜绿假单胞菌产生抗药性。在受感染的植入小鼠模型中，GMC-2 介导的先天性免疫和适应性免疫可有效消除铜绿假单胞菌生物膜。这些发现提供了一种促进生物分子与金属离子结合的通用方法，并强调了精确的 ROS 调节平台在启动针对细菌生物膜感染的内源性和外源性免疫激活中的关键作用。

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引用次数: 0