Materials Science & Engineering C-Materials for Biological Applications最新文献_第9页

Laminin expression profiles of osteogenic-and chondrogenic-induced dECM sheets 成骨和软骨诱导的dECM薄片的层粘连蛋白表达谱。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-30 DOI: 10.1016/j.bioadv.2024.214127

Yuting Feng , Zhiwei Jiang , Chaozhen Chen , Ling Hu , Qifeng Jiang , Yuchen Wang , Zhenxuan Cheng , Fang Wang , Guoli Yang , Ying Wang

Decellularized extracellular matrix sheets (dECMSs) produced by stem cells have attracted attention because they preserve the natural biological activity of the ECM to direct lineage-specific differentiation with less immunogenicity. As a core ECM protein, laminin modulates cellular phenotype and differentiation. Nevertheless, no studies thus far have explored the distribution and abundance of laminins in diverse dECMSs. Herein, we first compared the differential expression of laminins among dECMSs in osteogenic-induced medium (OI-dECMS), chondrogenic-induced medium (CI-dECMS), and standard medium (dECMS), employing a defined mass spectrometry (MS)-based proteomic analysis. In vitro, dECMSs were verified to be successfully decellularized. Cluster analysis identified a marked fluctuation in the expression of 7 laminins and 17 laminin-associated proteins in OI-dECMS vs dECMS and CI-dECMS vs dECMS. Two significantly changed pathways were selected from the KEGG pathway enrichment analysis: the FAK/ERK pathway and the PI3K/AKT pathway.

Moreover, Alkaline Phosphatase (ALP) activity, Alcian blue staining, and RT-qPCR results for recellularization showed that CI-dECMS promotes chondrogenesis while OI-dECMS inhibits osteogenesis compared with dECMS. In vivo experiments were conducted to implant dECMSs in a rat osteochondral defect, demonstrating that dECMS and CI-dECMS promoted bone and cartilage repair. Furthermore, the inhibitory analysis was performed to verify the function of specific laminin isoforms modulating osteogenesis and chondrogenesis, which might be related to FAK/ERK and PI3K/AKT pathways. In summary, this study constructed dECMS, OI-dECMS, and CI-dECMS and uncovered the internal comprehensive molecular regulatory network centralized by laminins, thus proposing a biomimetic substitute for bone and cartilage regeneration.

由干细胞产生的脱细胞细胞外基质片（dECMSs）因其保留了ECM的天然生物活性而引起了人们的关注，以指导谱系特异性分化，而免疫原性较低。作为ECM的核心蛋白，层粘连蛋白调节细胞表型和分化。然而，到目前为止，还没有研究探讨层粘连蛋白在不同dECMSs中的分布和丰度。在本文中，我们首先比较了在成骨诱导培养基（OI-dECMS）、软骨诱导培养基（CI-dECMS）和标准培养基（dECMS）中dECMS中层粘胶蛋白的差异表达，采用了基于定义质谱（MS）的蛋白质组学分析。在体外，证实dECMSs成功脱细胞。聚类分析发现7个层粘连蛋白和17个层粘连蛋白相关蛋白的表达在i -dECMS和CI-dECMS中有明显的波动。从KEGG通路富集分析中选择了两个显著变化的通路：FAK/ERK通路和PI3K/AKT通路。此外，碱性磷酸酶（ALP）活性、阿利新蓝染色和细胞再化RT-qPCR结果显示，与dECMS相比，CI-dECMS促进软骨形成，而io -dECMS抑制骨形成。将dECMS植入大鼠骨软骨缺损的体内实验表明，dECMS和CI-dECMS促进骨软骨修复。此外，通过抑制分析验证了特定层粘连蛋白亚型调节成骨和软骨形成的功能，这可能与FAK/ERK和PI3K/AKT通路有关。综上所述，本研究构建了dECMS、OI-dECMS和CI-dECMS，揭示了内部以层合蛋白为中心的综合分子调控网络，提出了骨软骨再生的仿生替代品。

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引用次数: 0

The effect of osteoclasts on epigenetic regulation by long non-coding RNAs in osteoblasts grown on titanium with nanotopography 破骨细胞对纳米钛表面生长成骨细胞长链非编码rna表观遗传调控的影响

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-29 DOI: 10.1016/j.bioadv.2024.214128

Rayana Longo Bighetti-Trevisan , Luciana Oliveira Almeida , Jaqueline Isadora Reis Ramos , Gileade Pereira Freitas , Fabiola Singaretti Oliveira , Jonathan Alexander Robert Gordon , Coralee Elizabeth Tye , Gary Stephen Stein , Jane Barbara Lian , Janet Lee Stein , Adalberto Luiz Rosa , Marcio Mateus Beloti

Titanium (Ti) implant osseointegration is regulated by the crosstalk among bone cells that are affected by epigenetic machinery, including the regulation of long non-coding RNAs (lncRNAs). Nanotopography Ti (Ti Nano) induces the differentiation of osteoblasts that are inhibited by osteoclasts through epigenetic mechanisms. Thus, we hypothesize that osteoclasts affect lncRNA expression in Ti Nano-cultivated osteoblasts. Osteoblasts were grown on Ti Nano and Ti Control that were then co-cultured with osteoclasts for 48 h. Using RNAseq, we identified 252 modulated lncRNAs in osteoblasts regulated by both surfaces of Ti, but mainly in Ti Nano-cultivated osteoblasts. A negative correlation was observed between Kcnq1ot1 and the mRNAs of Alpl, Bglap, Bmp8a, Col1a1, and Vim in Ti Nano-cultivated osteoblasts with osteoclasts. The pull-down indicated that Bglap mRNA is a direct target of Kcnq1ot1, with enhanced physical interaction in Ti Nano-cultivated osteoblasts, and greater osteoclast inhibition than the Ti Control. The bone marker expression at the levels of mRNA and protein were downregulated by the Kcnq1ot1 silencing, indicating its pivotal role in osteoblast differentiation. These results showed that nanostructured Ti surface modulates the osteoblast–osteoclast crosstalk, at least in part, through the regulation of lncRNA expression in osteoblasts. We demonstrate that the lncRNA Kcnq1ot1 directly interacts with Bglap mRNA, and this interaction is enhanced by nanotopography and reduced by osteoclasts with greater intensity in Ti Nano-cultivated osteoblasts. These findings confirm the molecular mechanisms associated with the high osteogenic potential of nanotopography and can potentially support osteointegration of dental and skeletal prostheses.

钛（Ti）种植体骨整合受表观遗传机制影响的骨细胞间的串扰调控，包括长链非编码rna （lncRNAs）的调控。纳米形貌钛（Ti Nano）通过表观遗传机制诱导被破骨细胞抑制的成骨细胞分化。因此，我们假设破骨细胞影响钛纳米培养成骨细胞中lncRNA的表达。成骨细胞分别在Ti Nano和Ti Control上生长，然后与破骨细胞共培养48小时。使用RNAseq，我们在受Ti两种表面调控的成骨细胞中鉴定出252种可调节的lncrna，但主要存在于Ti纳米培养的成骨细胞中。在钛纳米培养的破骨细胞中，Kcnq1ot1与Alpl、Bglap、Bmp8a、Col1a1、Vim mrna呈负相关。下拉结果表明，Bglap mRNA是kcnqot1的直接靶点，在Ti纳米培养的成骨细胞中具有增强的物理相互作用，并且比Ti对照具有更大的破骨细胞抑制作用。kcnqot1沉默后，骨标志物mRNA和蛋白水平表达下调，提示其在成骨细胞分化中起关键作用。这些结果表明，纳米结构的钛表面至少在一定程度上通过调控成骨细胞中lncRNA的表达来调节成骨细胞与破骨细胞的串扰。我们发现lncRNA kcnqot1直接与Bglap mRNA相互作用，并且在钛纳米培养的成骨细胞中，这种相互作用被纳米形貌增强，被破骨细胞减弱，且强度更大。这些发现证实了与纳米形貌高成骨潜能相关的分子机制，并可能支持牙齿和骨骼假体的骨整合。

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引用次数: 0

Hydrogel biomimetic skin inspired by human skin for resisting bacterial infection 仿生水凝胶皮肤，灵感来自人类皮肤，用于抵抗细菌感染

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-28 DOI: 10.1016/j.bioadv.2024.214126

Junfang Chang , Weijun Wu , Ranran Wu , Zhiyong Guo , Sui Wang , Jie Mao

The flexible surface and chemical compatibility of hydrogels render them particularly appealing for research and development in antibacterial materials. However, designing tough hydrogels with multiple antibacterial mechanisms simultaneously remains a challenge. Inspired by the human skin, a hydrogel with bacterial antifouling, detection, and inactivation functions has been prepared using zwitterionic [2-(methylacrylyl) ethyl] dimethyl-(3-propyl sulfonate) ammonium hydroxide (SBMA) as the matrix and cadmium telluride quantum dots functionalised with cysteamine (CA-CdTe QDs) as the filler through micelle copolymerisation technology, achieving the integration of multiple antimicrobial mechanisms. The experimental analysis demonstrated that the SBMA/CA-CdTe/Micelle (SCM) hydrogel exhibited antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus), proving its excellent broad-spectrum antibacterial properties. Introducing micelles imparts excellent hydrophilicity, stability, and mechanical properties to the SCM hydrogel. Moreover, the SCM hydrogels possess significant self-adhesive properties, enabling them to function as biomimetic skin that tightly adheres to target surfaces, protecting them from bacterial contamination. In addition, the SCM hydrogel biomimetic skin exhibits good electrical conductivity and biocompatibility, capable of converting the motion amplitude of human activity into stable electrical signals, suggesting potential for human motion sensing applications. Overall, the SCM hydrogel biomimetic skin designed in this work, as a multifunctional antibacterial platform, effectively reduces bacterial contamination and holds significant application potential in healthcare and life sciences.

水凝胶的柔韧表面和化学相容性使它们在抗菌材料的研究和开发中特别具有吸引力。然而，同时设计具有多种抗菌机制的坚韧水凝胶仍然是一个挑战。受人体皮肤的启发，以两性离子[2-（甲基丙烯基）乙基]二甲基-（3-丙基磺酸盐）氢氧化铵（SBMA）为基质，以半胱胺（CA-CdTe量子点）为填料，通过胶束共聚技术制备了具有细菌防污、检测和灭活功能的水凝胶，实现了多种抗菌机制的集成。实验分析表明，SBMA/CA-CdTe/胶束（SCM）水凝胶对革兰氏阴性菌（大肠杆菌）和革兰氏阳性菌（金黄色葡萄球菌）均具有抗菌活性，证明其具有良好的广谱抗菌性能。引入胶束使SCM水凝胶具有优异的亲水性、稳定性和机械性能。此外，SCM水凝胶具有显著的自粘特性，使其能够作为仿生皮肤紧密粘附在目标表面，保护其免受细菌污染。此外，SCM水凝胶仿生皮肤具有良好的导电性和生物相容性，能够将人体活动的运动幅度转化为稳定的电信号，具有人体运动传感应用的潜力。综上所述，本课题设计的SCM水凝胶仿生皮肤作为一种多功能抗菌平台，可有效减少细菌污染，在医疗保健和生命科学领域具有重要的应用潜力。

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引用次数: 0

The application and prospects of drug delivery systems in idiopathic pulmonary fibrosis 药物输送系统在特发性肺纤维化中的应用与展望

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-28 DOI: 10.1016/j.bioadv.2024.214123

Xi Zhang , Ling Zhang , Jiahua Tian , Yunfei Li , Manli Wu , Longju Zhang , Xiaofei Qin , Ling Gong

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease primarily affecting elderly individuals aged >65 years and has a poor prognosis. No effective treatment is currently available for IPF. The two antipulmonary fibrosis drugs nintedanib and pirfenidone approved by the FDA in the United States have somewhat decelerated IPF progression. However, the side effects of these drugs can lead to poor patient tolerance and compliance with the medications. Researchers have recently developed various methods for IPF treatment, such as gene silencing and pathway inhibitors, which hold great promise in IPF treatment. Nevertheless, the nonselectivity and nonspecificity of drugs often affect their efficacies. Drug delivery systems (DDS) are crucial for delivering drugs to specific target tissues or cells, thereby minimizing potential side effects, enhancing drug bioavailability, and reducing lung deposition. This review comprehensively summarizes the current state of DDS and various delivery strategies for IPF treatment (e.g., nano-delivery, hydrogel delivery, and biological carrier delivery) to completely expound the delivery mechanisms of different drug delivery carriers. Subsequently, the advantages and disadvantages of different DDS are fully discussed. Finally, the challenges and difficulties associated with the use of different DDS are addressed so as to accelerate their rapid clinical translation.

特发性肺纤维化（IPF）是一种间质性肺疾病，主要影响65岁以上的老年人，预后较差。目前还没有针对IPF的有效治疗方法。美国FDA批准的两种抗肺纤维化药物尼达尼布和吡非尼酮在一定程度上减缓了IPF的进展。然而，这些药物的副作用会导致患者对药物的耐受性和依从性差。研究人员最近开发了多种治疗IPF的方法，如基因沉默和途径抑制剂，这些方法在IPF治疗中具有很大的前景。然而，药物的非选择性和非特异性往往影响其疗效。药物输送系统（DDS）对于将药物输送到特定的靶组织或细胞至关重要，从而最大限度地减少潜在的副作用，提高药物的生物利用度，减少肺沉积。本文综合综述了DDS的研究现状以及IPF治疗的各种递送策略（如纳米递送、水凝胶递送、生物载体递送等），全面阐述了不同药物递送载体的递送机制。随后，对不同DDS的优缺点进行了充分的讨论。最后，讨论了使用不同DDS的挑战和困难，以加快其快速临床转化。

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引用次数: 0

Glycopeptide microneedles triggering the ECM process to promote fibroblast viability for anti-aging treatments 糖肽微针触发ECM过程，促进成纤维细胞活力，用于抗衰老治疗

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-26 DOI: 10.1016/j.bioadv.2024.214124

Wenjie Zhang , Qing Shao , Hua Zhong , Yingying Yang , Ruixue Li , Yaxian Liu , Yi Hu , Penghui Wang , Bo Chi

Skin anti-aging remains challenging due to the cumulative detrimental effects within the intricate microenvironment. Here, we present glycopeptide hydrogel (γ-PGA/HA) microneedle patches composed of poly (γ-glutamic acid) and hyaluronic acid as a potential solution. These microneedles aim to effectively penetrate the skin barrier while remodeling extracellular matrix to regulate the skin microenvironment. To align with clinical requirements, the functional properties of microenvironment regulation materials are characterized by testing the water absorption and retention, redox balance, and inflammatory microenvironment regulation ability. The γ-PGA/HA exhibited remarkable moisturizing, biocompatibility, fibroblast viability promotion, ROS consumption, and TNF-α inhibiting effects. Histological analysis provides empirical evidence supporting the functional efficacy of the microneedle, thus validating the anti-skin-aging potential of a model that mimics natural aging processes. Therefore, γ-PGA/HA holds promise for regulating the skin microenvironment, offering potential applications in skin aging treatments.

由于复杂的微环境中累积的有害影响，皮肤抗衰老仍然具有挑战性。在这里，我们提出了由聚γ-谷氨酸和透明质酸组成的糖肽水凝胶（γ-PGA/HA）微针贴片作为一种潜在的解决方案。这些微针旨在有效穿透皮肤屏障，同时重塑细胞外基质，调节皮肤微环境。为配合临床需要，对微环境调节材料的功能特性进行了表征，测试了材料的吸水潴留、氧化还原平衡、炎症微环境调节能力。γ-PGA/HA具有显著的保湿、生物相容性、促进成纤维细胞活力、消耗ROS和抑制TNF-α的作用。组织学分析提供了支持微针功能功效的经验证据，从而验证了模拟自然衰老过程的模型的抗皮肤衰老潜力。因此，γ-PGA/HA具有调节皮肤微环境的潜力，在皮肤衰老治疗中具有潜在的应用前景。

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引用次数: 0

Articular cartilage regeneration with a microgel as a support biomaterial. A rabbit knee model 以微凝胶为支撑材料的关节软骨再生。兔膝模型

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-26 DOI: 10.1016/j.bioadv.2024.214125

Javier Zurriaga Carda , Carmen María Antolinos-Turpin , Joaquín Ródenas-Rochina , Lara Milián , Julia Pla-Salom , Zakaria Oguir , María Sancho-Tello , Manuel Mata , Carmen Carda , Gloria Gallego-Ferrer , José Luis Gómez Ribelles

Articular cartilage has limited regenerative capacity, so focal lesions generate mechanical stress in the joint that induces an aggravation of the damage, which ultimately leads to osteoarthritis. We recently suggested the use of microgels at the site of the cartilage defect, as a support material, to generate a biomechanical environment where pluripotent cells differentiate towards the hyaline cartilage phenotype. Here we propose a chondral regeneration strategy based on subchondral bone injury, and filling the defect site with an agglomerate of two types of microspheres, some rigid made of a biodegradable polyester (40 μm mean diameter), and others with a gel consistency made of platelet-rich plasma obtained from circulating blood (70–110 μm diameter). A 3-mm diameter defect was made in the articular cartilage of the knee joint in rabbits, exposing the subchondral bone, in which incisions were made to produce bleeding. Microgels were implanted filling the defect, which was covered with a synthetic membrane of the same polyester. Three months later, cartilage regeneration was analyzed according to the International Cartilage Repair Society (ICRS) guidelines. The newly formed tissue showed histological characteristics of hyaline cartilage, being significantly closer to native cartilage than when only the membrane was implanted, mainly in parameters such as tissue (70.0 ± 20.9) and cell morphologies (100.0 ± 0.0), and surface architecture (90.0 ± 22.4) and assessment (70.0 ± 11.2), with native tissue having a value of 100. Polyester microspheres and membrane were not bioreabsorbed during the three months, but rather moved towards the subchondral bone, leaving space for the organization of the newly formed tissue.

关节软骨的再生能力有限，因此局灶性病变在关节内产生机械应力，导致损伤加重，最终导致骨关节炎。我们最近建议在软骨缺损部位使用微凝胶作为支撑材料，以产生一个生物力学环境，使多能细胞向透明软骨表型分化。在这里，我们提出了一种基于软骨下骨损伤的软骨再生策略，并用两种类型的微球团填充缺损部位，一些是由可生物降解聚酯（平均直径40 μm）制成的刚性微球，另一些是由来自循环血液的富含血小板的血浆（直径70-110 μm）制成的凝胶状微球。在兔膝关节关节软骨处做了一个直径3毫米的缺损，暴露了软骨下骨，在软骨下做了切口导致出血。植入微凝胶填充缺陷，并用相同的聚酯合成膜覆盖。3个月后，根据国际软骨修复协会（ICRS）的指南分析软骨再生情况。新形成的组织表现出透明软骨的组织学特征，与仅植入膜时相比，明显更接近天然软骨，主要表现在组织（70.0±20.9）和细胞形态（100.0±0.0）、表面结构（90.0±22.4）和评估（70.0±11.2）等参数上，天然组织的值为100。聚酯微球和膜在三个月内没有被生物重新吸收，而是向软骨下骨移动，为新形成的组织留下空间。

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引用次数: 0

siRNA-based nanotherapeutic approaches for targeted delivery in rheumatoid arthritis 基于 siRNA 的纳米治疗方法用于类风湿性关节炎的靶向给药。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-19 DOI: 10.1016/j.bioadv.2024.214120

Sweta Sawan , Ankita Kumari , Ankit Majie , Arya Ghosh , Varnita Karmakar , Nimmy Kumari, Santanu Ghosh, Bapi Gorain

Rheumatoid arthritis (RA), characterized as a systemic autoimmune ailment, predominantly results in substantial joint and tissue damage, affecting millions of individuals globally. Modern treatment modalities are being explored as the traditional RA therapy with non-specific immunosuppressive drugs showcased potential side effects and variable responses. Research potential with small interfering RNA (siRNA) depicted potential in the treatment of RA. These siRNA-based therapies could include genes encoding pro-inflammatory cytokines like TNF-α, IL-1, and IL-6, as well as other molecular targets such as RANK, p38 MAPK, TGF-β, Wnt/Fz complex, and HIF. By downregulating the expression of these genes, siRNA-based nanoformulations can attenuate inflammation, inhibit immune system dysregulation, and prevent tissue damage associated with RA. Strategies of delivering siRNA molecules through nanocarriers could be targeted to treat RA effectively, where specific genes associated with this autoimmune disease pathology can be selectively silenced. Additionally, simultaneous targeting of multiple molecular pathways may offer synergistic therapeutic benefits, potentially leading to more effective and safer therapeutic strategies for RA patients. This review critically highlights the in-depth pathology of RA, RNA interference-mediated molecular targets, and nanocarrier-based siRNA delivery strategies, along with the challenges and opportunities to harbor future solutions.

类风湿性关节炎（RA）是一种全身性自身免疫性疾病，主要导致关节和组织严重受损，影响着全球数百万人。由于使用非特异性免疫抑制剂的传统 RA 治疗方法存在潜在的副作用和不同的反应，因此人们正在探索现代治疗方法。小干扰 RNA（siRNA）的研究显示了治疗 RA 的潜力。这些基于 siRNA 的疗法可包括编码 TNF-α、IL-1 和 IL-6 等促炎细胞因子的基因，以及 RANK、p38 MAPK、TGF-β、Wnt/Fz 复合物和 HIF 等其他分子靶点。通过下调这些基因的表达，基于 siRNA 的纳米制剂可减轻炎症反应、抑制免疫系统失调并防止与 RA 相关的组织损伤。通过纳米载体递送 siRNA 分子的策略可以有针对性地有效治疗风湿性关节炎，选择性地沉默与这种自身免疫性疾病病理相关的特定基因。此外，同时靶向多种分子通路可能会产生协同治疗效果，从而为 RA 患者带来更有效、更安全的治疗策略。本综述重点介绍了 RA 的深入病理、RNA 干扰介导的分子靶点、基于纳米载体的 siRNA 递送策略，以及未来解决方案所面临的挑战和机遇。

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引用次数: 0

Janus radial nanofiber patch with leak-proof, antimicrobial, and osteogenic integration for skull base reconstruction 用于颅底重建的具有防漏、抗菌和成骨整合功能的 Janus 径向纳米纤维贴片

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-19 DOI: 10.1016/j.bioadv.2024.214122

Xiaomei Xia , Zhen Yang , Hongshui Wang , Werner E.G. Müller , Xiaohong Wang , Lei Yang , Huan Zhou , Yi Xia , Chunyong Liang

During transsphenoidal surgery to remove pituitary adenomas, the structures of the skull base consisting of the dura mater and skull base bones are destroyed, making it crucial to restore the natural structure of the skull base. We crafted a dual-layer Janus fiber membrane utilizing the layer-by-layer electrospinning technique, comprising an osteoblast layer and a leak-proof antimicrobial layer. Specifically, RPG-1%PCPP radially aligned nanofibrous membranes (osteoblasts) can promote directional cell migration and facilitate cellular osteogenic differentiation. TPC nanofibrous membranes (leak-proof antimicrobial layer) can prevent fluid leakage while releasing antimicrobials for resisting bacterial infections. Bacteriostatic tests showed that cefazolin had a good inhibitory ability against both E. coli and S. aureus. RT-PCR showed that radial fiber membrane loaded with PCPP promoted the expression of ALP and BMP-2 genes, thereby promoting osteogenic differentiation of cells. Animal experiments showed that the BV/TV in the TPC/RPG-1%PCPP fiber membrane group was significantly higher than that in the blank group, indicating that TPC/RPG-1%PCPP could promote bone tissue regeneration.

在经蝶窦手术切除垂体腺瘤的过程中，由硬脑膜和颅底骨组成的颅底结构遭到破坏，因此恢复颅底的自然结构至关重要。我们利用逐层电纺技术制作了双层 Janus 纤维膜，包括成骨细胞层和防漏抗菌层。具体来说，RPG-1%PCPP径向排列的纳米纤维膜（成骨细胞）可促进细胞定向迁移，促进细胞成骨分化。TPC 纳米纤维膜（防漏抗菌层）可防止液体渗漏，同时释放抗菌剂以抵抗细菌感染。抑菌测试表明，头孢唑啉对大肠杆菌和金黄色葡萄球菌都有很好的抑制能力。RT-PCR 试验表明，载入 PCPP 的径向纤维膜可促进 ALP 和 BMP-2 基因的表达，从而促进细胞的成骨分化。动物实验表明，TPC/RPG-1%PCPP纤维膜组的BV/TV明显高于空白组，表明TPC/RPG-1%PCPP可促进骨组织再生。

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引用次数: 0

Biotinylated platinum(IV)-conjugated graphene oxide nanoparticles for targeted chemo-photothermal combination therapy in breast cancer 生物素化铂（IV）共轭氧化石墨烯纳米粒子用于乳腺癌的靶向化疗-光热联合疗法。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-19 DOI: 10.1016/j.bioadv.2024.214121

Asif Mohd Itoo, Milan Paul, Naitik Jain, Varshini Are, Ankita Singh, Balaram Ghosh, Swati Biswas

Graphene oxide (GO) and GO-based nanocomposites are promising in drug delivery and photothermal therapy due to their exceptional near-infrared optical absorption and high specific surface area. In this study, we have effectively conjugated an oxaliplatin (IV) prodrug, PEGylated graphene oxide, and PEGylated biotin (PB) in a single platform for breast cancer treatment. This platform demonstrates promising prospects for targeted drug delivery and the synergistic application of photothermal-chemotherapy when exposed to NIR-laser irradiation. The resulting nanocomposite (GO(OX)PB (1/1/0.2) NPs) displayed an exceptionally large surface area, minimal particle size (195.7 nm), specific targeting capabilities, a high drug load capacity (43.56 %) and entrapment efficiency (89.48 %) and exhibit excellent photothermal conversion efficiency and photostability when exposed to NIR-laser irradiation (808 nm). The therapeutic effectiveness was assessed both in vitro and in vivo conditions employing human breast cancer cells (MCF-7), mouse mammary gland adenocarcinoma cells (4T1), and 4T1-Luc tumor-bearing mouse models. The findings demonstrated that GO(OX)PB (1/1/0.2) NPs (+L) were highly effective in causing significant cytotoxicity, G2/M phase cell cycle arrest, ROS generation, mitochondrial membrane depolarization, apoptosis, and photothermal effect. This resulted in a greater percentage of cell death compared to free OX, GO(OX)PEG (1/1/0.2) NPs (±L), and GO(OX)PB (1/1/0.2) NPs (−L). The in vivo therapeutic studies on 4T1-Luc tumor-bearing mice revealed that a combination of GO(OX)PB (1/1/0.2) NPs (+L) caused complete disappearance of the tumor, no tumor recurrence, prolonged survival, reduced lung metastasis, and mitigated nephrotoxicity. The serum and blood analysis demonstrated minimal systemic toxicity of GO(OX)PB (1/1/0.2) NPs. The developed nanoplatform, in this context, may serve as a potential nanomedicine to address conventional nephrotoxicity in breast cancer and prevent metastasis by combining chemo-photothermal therapy.

氧化石墨烯（GO）和基于 GO 的纳米复合材料具有优异的近红外光学吸收能力和高比表面积，因此在药物输送和光热治疗方面大有可为。在这项研究中，我们将奥沙利铂（IV）原药、PEG 化氧化石墨烯和 PEG 化生物素（PB）有效地共轭在一个平台上，用于乳腺癌治疗。该平台展示了靶向给药和在近红外激光照射下协同应用光热化疗的广阔前景。所制备的纳米复合材料（GO(OX)PB (1/1/0.2) NPs）具有超大比表面积、最小粒径（195.7 nm）、特异性靶向能力、高载药量（43.56 %）和夹带效率（89.48 %），并且在近红外激光照射（808 nm）下表现出优异的光热转换效率和光稳定性。研究人员利用人体乳腺癌细胞（MCF-7）、小鼠乳腺腺癌细胞（4T1）和 4T1-Luc 肿瘤小鼠模型对其治疗效果进行了体内外评估。研究结果表明，GO(OX)PB（1/1/0.2）NPs（+L）具有显著的细胞毒性、G2/M 期细胞周期停滞、ROS 生成、线粒体膜去极化、细胞凋亡和光热效应。与游离 OX、GO(OX)PEG (1/1/0.2) NPs (±L)和 GO(OX)PB (1/1/0.2) NPs (-L) 相比，细胞死亡的比例更高。对 4T1-Luc 肿瘤小鼠进行的体内治疗研究表明，GO(OX)PB (1/1/0.2) NPs (+L) 组合可使肿瘤完全消失，无肿瘤复发，延长生存期，减少肺转移，减轻肾毒性。血清和血液分析表明，GO(OX)PB (1/1/0.2) NPs 的全身毒性极小。在这种情况下，所开发的纳米平台可作为一种潜在的纳米药物，通过结合化疗和光热疗法来解决乳腺癌的传统肾毒性问题并防止转移。

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引用次数: 0

Exacerbated hepatotoxicity in in vivo and in vitro non-alcoholic fatty liver models by biomineralized copper sulfide nanoparticles 生物矿化硫化铜纳米颗粒在体内和体外非酒精性脂肪肝模型中加剧的肝毒性

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-18 DOI: 10.1016/j.bioadv.2024.214117

Jinbin Cui , Gang Zhao , Wei Xie , Yang Yang , Xing Fu , Hezhang Meng , He Liu , Mengfei Tan , Dandan Chen , Chao Rong , Yangyun Wang , Yong Wang , Leshuai W. Zhang

Copper sulfide nanoparticles (NPs) synthesized through biomineralization have significant commercial potential as photothermal agents, while the safety evaluation of these NPs, especially for patients with non-alcoholic fatty liver (NAFL), remains insufficient. To explore the differential hepatotoxicity of copper sulfide NPs in NAFL conditions, we synthesized large-sized (LNPs, 15.1 nm) and small-sized (SNPs, 3.5 nm) BSA@Cu_2-xS NPs. A NAFL rat model fed with high fat diet (HFD) was successfully established for a 14-day subacute toxicity study by daily repeated administration of BSA@Cu_2-xS NPs. Our findings from serum biochemistry and histopathological examinations revealed that copper sulfide at both sizes NPs induced more pronounced liver damage in NAFL rats than rats fed with normal diet. Transcriptome sequencing analysis showed that LNPs activated inflammation and DNA damage repair pathways in the livers of NAFL rats, while SNPs displayed minimal inflammation. A three-dimensional spheroid model of NAFL developed in our in-house cell spheroid culture honeycomb chips demonstrated that LNPs, but not SNPs, triggered a distinct release of inflammatory factors and increased reactive oxygen species through Kupffer cells. These results highlight that NAFL condition exacerbated the hepatotoxicity of BSA@Cu_2-xS NPs, with SNPs emerging as safer photothermal agents compared to LNPs, suggesting superior potential for clinical applications.

通过生物矿化合成的硫化铜纳米粒子（NPs）作为光热剂具有巨大的商业潜力，但对这些NPs的安全性评估，尤其是对非酒精性脂肪肝（NAFL）患者的安全性评估仍然不足。为了探索硫化铜 NPs 在非酒精性脂肪肝条件下的不同肝毒性，我们合成了大尺寸（LNPs，15.1 nm）和小尺寸（SNPs，3.5 nm）BSA@Cu2-xS NPs。通过每天重复给药 BSA@Cu2-xS NPs，成功建立了以高脂饮食（HFD）喂养的 NAFL 大鼠模型，并进行了为期 14 天的亚急性毒性研究。血清生化和组织病理学检查结果表明，与正常饮食喂养的大鼠相比，两种尺寸的硫化铜 NPs 对 NAFL 大鼠肝脏的损伤更为明显。转录组测序分析表明，LNPs 激活了非酒精性脂肪肝大鼠肝脏中的炎症和 DNA 损伤修复途径，而 SNPs 则显示出极少的炎症。我们在内部细胞球形培养蜂巢芯片中开发的非酒精性脂肪肝三维球形模型表明，LNPs（而非 SNPs）会通过 Kupffer 细胞引发炎症因子的明显释放和活性氧的增加。这些结果突出表明，非酒精性脂肪肝会加剧 BSA@Cu2-xS NPs 的肝毒性，与 LNPs 相比，SNPs 成为更安全的光热制剂，这表明 SNPs 具有更优越的临床应用潜力。

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引用次数: 0