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Roadmap to Nanomedical Applications: Nanotoxicology and In Vitro Guidelines for Lanthanide-Doped Luminescence Nanothermometers 纳米医学应用路线图:掺杂镧系发光纳米温度计的纳米毒理学和体外指南
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-27 DOI: 10.1002/anbr.202500003
Simona Premcheska, Andre G. Skirtach, Anna M. Kaczmarek

Lanthanide-based luminescence nanothermometry has demonstrated unprecedented advantages in the development of nanotheranostic platforms for potential medical applications, yet despite exponential research progress and great enthusiasm across various related disciplines, a swift bench-to-bedside translation seems to be still out of reach. This is predominantly related to fundamental research issues at the preclinical stage, such as complex nanomaterials design, incomplete optimization, fragmented characterization, and insufficient validation of nanothermometer performance in physiological environments. The main impediments currently are important biophysicochemical issues that must be addressed comprehensively, first and foremost in available in vitro systems, before going on to in vivo investigations. This review outlines a critical perspective, as well as a route of suggestions and underexplored aspects to address and significantly minimize the existing translational gap.

基于镧系元素的发光纳米热测量在纳米治疗平台的发展中显示出了前所未有的优势,这些平台具有潜在的医疗应用,然而,尽管各种相关学科的研究取得了指数级的进展和巨大的热情,但从实验室到病床的快速转化似乎仍然遥不可及。这主要与临床前阶段的基础研究问题有关,例如复杂的纳米材料设计,不完整的优化,碎片化的表征,以及在生理环境中纳米温度计性能的不充分验证。目前的主要障碍是重要的生物物理化学问题,在进行体内研究之前,必须首先在体外系统中全面解决这些问题。这篇综述概述了一个批判性的观点,以及解决和显著减少现有翻译差距的建议和未被探索的方面。
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引用次数: 0
Memory Effect of Bacteria-Killing Properties of Piezo-Catalysts Nanomaterials through Defect Engineering 基于缺陷工程的纳米压电催化剂杀菌性能记忆效应研究
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-27 DOI: 10.1002/anbr.202300144
Omid Amiri, Karzan A. Qurbani, Karukh A. Babakr, Peshang Kh. Omer, L. Jay Guo, Hastyar Hama Rashid Najmuldeen, Martin Bertau, Peshawa H. Mahmood, Sangar S. Ahmed, Mohammed A. Jamal

This study investigates the effects of piezo-catalysts on sterilizing surfaces. The memory effects in three piezo-catalysts, ZnO, CuO, and SiO2 are discovered, which are produced by a calcination process. After applying mechanical force to these materials, they retain an antibacterial effect for a period of days. With this discovery, it is possible to combat antibiotic-resistant bacteria by using piezo materials on hospital floors or operating rooms that can kill bacteria just by walking on them. The results show that ZnO, CuO, and SiO2 are capable of killing bacteria even after being subjected to mechanical force for 9 days. The memory effect duration can be influenced by a variety of factors, including the calcination temperature, the storage condition after ultrasonication, the drying temperature after ultrasonication, and the solvent in which the piezo-catalyst is ultrasonicated. When ZnO, CuO, and SiO2 are kept under a vacuum in a dark environment, the piezo effect remains almost constant for 11 days after sonication.

本研究探讨了压电催化剂对灭菌表面的影响。研究了煅烧法制备的ZnO、CuO和SiO2三种压电催化剂的记忆效应。在对这些材料施加机械力后,它们在一段时间内保持抗菌效果。有了这一发现,在医院地板或手术室使用压电材料,只要在上面行走就能杀死细菌,就有可能对抗耐抗生素细菌。结果表明,ZnO、CuO和SiO2在机械力作用9天后仍能杀灭细菌。记忆效应持续时间受多种因素的影响,包括煅烧温度、超声处理后的储存条件、超声处理后的干燥温度、超声处理的溶剂等。当ZnO、CuO和SiO2在黑暗环境中真空保存时,超声后的压电效应在11天内几乎保持不变。
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引用次数: 0
Induction of Cell Death by Combined Treatment with Photosensitizer-Chitosan Nanoparticles and the Ferroptosis Inducer RSL3 in Breast Cancer Cell Lines 光敏剂-壳聚糖纳米颗粒与铁下垂诱导剂RSL3联合作用诱导乳腺癌细胞死亡
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-23 DOI: 10.1002/anbr.202400208
Marek Feith, Saikat Das Sajib, Anne Grethe Myrann, Anders Høgset, Pablo Garrido, Alfredo Martinez, Erik Knutsen, Kirsten Sandvig, Tore Skotland, Gunhild Mari Mælandsmo, Tore-Geir Iversen

Breast cancer, a prevalent malignancy worldwide, includes the triple-negative subtype (TNBC) characterized by poor treatment outcomes. TNBC has been shown to be sensitive to ferroptotic cell death, an iron-dependent cell death mechanism involving reactive oxygen species (ROS) and lipid peroxidation. Herein, biodegradable tetraphenylchlorin-conjugated chitosan nanoparticles (TPC-CS NPs) in combination with the free ferroptosis inducer RSL3 is used in MCF7 (hormone receptor-positive, epithelial) and MDA-MB-231 (hormone receptor-negative, mesenchymal-like) breast cancer cell lines. The results show that RSL3 treatment has no cytotoxic effect in MCF7 and there is no enhanced sensitivity when combined with TPC-CS NPs, while the combination sensitizes MDA-MB-231 cells. Western blot analysis reveals that the combined treatment decreases and differently affects GPX4 levels and the ratio between the two GPX isoforms in the two cell lines. In MDA-MB-231 cells, the combined treatment shows enhanced effects on lipid peroxidation, mitochondrial potential, and basal and maximal respiration, as compared to single treatments. Finally, ferroptosis expression signatures distinguish breast cancer cell lines with an increasing score in mesenchymal-like cells. Moreover, the signatures correlate with breast cancer subtypes, exhibiting the highest scores in subtypes rich in mesenchymal-like cells, particularly basal-like and claudin-low tumors, suggesting their susceptibility to ferroptosis induction.

乳腺癌是一种世界范围内普遍存在的恶性肿瘤,包括三阴性亚型(TNBC),其特点是治疗效果差。TNBC已被证明对铁致细胞死亡敏感,铁致细胞死亡是一种涉及活性氧(ROS)和脂质过氧化的铁依赖性细胞死亡机制。本研究将可生物降解的四苯基氯偶联壳聚糖纳米颗粒(TPC-CS NPs)与游离铁凋亡诱导剂RSL3联合应用于MCF7(激素受体阳性,上皮细胞)和MDA-MB-231(激素受体阴性,间质样)乳腺癌细胞系。结果显示,RSL3治疗对MCF7无细胞毒作用,与TPC-CS NPs联合使用时,其敏感性没有增强,而与TPC-CS NPs联合使用时,对MDA-MB-231细胞增敏。Western blot分析显示,联合处理降低了两种细胞系GPX4水平,并对两种GPX亚型的比值有不同程度的影响。在MDA-MB-231细胞中,与单一处理相比,联合处理对脂质过氧化、线粒体电位、基础呼吸和最大呼吸的影响增强。最后,铁下垂表达特征区分乳腺癌细胞系,在间充质样细胞中评分增加。此外,这些特征与乳腺癌亚型相关,在富含间充质样细胞的亚型中表现出最高的分数,特别是基底样和低cludin肿瘤,表明它们对铁下垂诱导的易感性。
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引用次数: 0
Hydrophilic Particles Exit While Hydrophobic Particles Persist Following In Vivo Biodegradation of Nanoparticle-Laden Polymeric Devices 携带纳米粒子的聚合物装置在体内生物降解后,亲水粒子退出,而疏水粒子继续存在
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.1002/anbr.202500005
Kendell M. Pawelec, Jeremy M. L. Hix, Matti Kiupel, Peter J. Bonitatibus Jr., Erik M. Shapiro

Longitudinally monitoring biomedical devices postimplantation can improve patient outcomes by allowing targeted intervention during healing. Most polymeric devices are not visible via biomedical imaging technologies. Incorporation of nanoparticle contrast agents into polymer matrices creates imageable devices, but understanding and controlling nanoparticle clearance from the implant site after polymer degradation is needed for clinical translation. To achieve homogeneous distribution throughout biomedical devices, nanoparticle surface chemistry, particularly hydrophobicity, is often manipulated to generate stable suspensions during manufacture. As nanoparticle surface chemistry is a key parameter determining blood circulation, the effects of nanoparticle hydrophilicity on tissue clearance of nanoparticles from implant sites following polymeric device degradation are investigated. Hydrophilic and hydrophobic radiopaque tantalum oxide (TaOx) nanoparticles are incorporated at 10 wt% tantalum into gelatin phantoms. In vitro, the diffusion coefficient of released hydrophilic nanoparticles after phantom degradation is significantly greater than hydrophobic nanoparticles, 1.29 ± 0.26 × 10−5 and 0.40 ± 0.16 × 10−5 cm2 s−1, respectively. After subcutaneous implantation in mouse and subsequent phantom degradation, hydrophilic nanoparticles clear skin and muscle tissue within 24 h, whereas hydrophobic nanoparticles remained at the implant site >14 days without change in radiopacity. This clearly demonstrates that nanoparticle surface chemistry must be balanced for initial device manufacturing and final excretion.

纵向监测生物医学设备植入后可以改善患者的结果,允许在愈合期间进行有针对性的干预。大多数聚合物装置通过生物医学成像技术是不可见的。将纳米颗粒造影剂掺入聚合物基质中可以创造出可想象的装置,但了解和控制聚合物降解后纳米颗粒从植入部位清除是临床转化所需要的。为了在整个生物医学设备中实现均匀分布,纳米颗粒的表面化学,特别是疏水性,通常在制造过程中被操纵以产生稳定的悬浮液。由于纳米颗粒表面化学是决定血液循环的关键参数,因此研究了纳米颗粒亲水性对聚合物装置降解后植入部位组织清除纳米颗粒的影响。亲水性和疏水性的不透射线氧化钽(TaOx)纳米颗粒以10 wt%的钽掺入明胶幻影中。体外实验结果表明,降解后释放的亲水纳米颗粒的扩散系数显著大于疏水纳米颗粒,分别为1.29±0.26 × 10−5和0.40±0.16 × 10−5 cm2 s−1。在小鼠皮下植入和随后的幻影降解后,亲水纳米颗粒在24小时内清除皮肤和肌肉组织,而疏水纳米颗粒在植入部位停留14天,没有改变放射透明度。这清楚地表明,纳米颗粒表面化学必须平衡初始设备制造和最终排泄。
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引用次数: 0
Highly Loaded Reactive Oxygen Species–Responsive Theranostic Lenvatinib-Prodrug Nanoparticles Produced by Dispersion Polymerization 分散聚合制备的高负荷活性氧反应治疗Lenvatinib-Prodrug纳米颗粒
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-18 DOI: 10.1002/anbr.202400187
Sarah Spiewok, Felicitas Jansen, Jiaying Han, Markus Lamla, Max von Delius, Christian Trautwein, Laura De Laporte, Alexander J. C. Kuehne

Nanoparticles represent a powerful class of materials for drug delivery, leveraging their small size for passive targeting through the enhanced permeability and retention effect in tumors. This universal approach in tumor targeting offers several advantages over free therapeutics, particularly when combined with imaging capabilities. While a plethora of nanoparticles exist for various imaging techniques, the number of nanoparticles with therapeutic functions is much smaller, due to the synthetic challenges present for incorporation and release of an active drug. Herein, a strategy to transform the tyrosine kinase inhibitor lenvatinib into a polymerizable prodrug monomer is presented, enabling its incorporation into biodegradable polyimidazole-based particles. This drug monomer is then polymerized and thus incorporated into the nanoparticles via direct arylation in a dispersion polymerization approach. The polyimidazole backbone allows for high drug loads of up to 90 wt%. Additionally, the photoacoustic properties of the polyimidazole nanoparticles are preserved after drug incorporation. Moreover, the backbone remains degradable upon exposure to hydrogen peroxide, facilitating drug release. This approach enables packaging of a drug, for which no prodrug approaches exist and which is therefore challenging to incorporate into particles due to limited functional groups. The result is a new theranostic nanoagent.

纳米颗粒代表了一种强大的药物递送材料,利用其小尺寸通过增强肿瘤的渗透性和滞留效应进行被动靶向。这种通用的肿瘤靶向方法比免费治疗有几个优势,特别是当与成像能力相结合时。虽然存在大量用于各种成像技术的纳米颗粒,但具有治疗功能的纳米颗粒的数量要少得多,这是由于活性药物的结合和释放所面临的合成挑战。本文提出了一种将酪氨酸激酶抑制剂lenvatinib转化为可聚合的前药单体的策略,使其能够融入可生物降解的聚咪唑基颗粒中。然后将该药物单体聚合,从而通过分散聚合方法中的直接芳基化纳入纳米颗粒中。聚咪唑骨架允许高达90% wt%的高药物负荷。此外,在药物掺入后,聚咪唑纳米颗粒的光声特性得以保留。此外,骨架在暴露于过氧化氢时仍可降解,促进药物释放。这种方法能够包装药物,因为没有前药方法存在,因此由于有限的官能团而难以将其纳入颗粒中。结果是一种新的治疗纳米剂。
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引用次数: 0
Inhibition of Biofilm Formation on Orthopedic Implants Based on Spider Silk Coatings Increases Survival of Galleria mellonella 抑制基于蜘蛛丝涂层的骨科植入物生物膜的形成可提高黑孢Galleria mellonella的存活率
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-10 DOI: 10.1002/anbr.202400160
Supun Mohotti, Gopala K. Mannala, Hendrik Bargel, Volker Alt, Thomas Scheibel

The microbial repellence of some spider silk-based materials makes them interesting candidates for biomedical applications. This study investigates the microbial repellent properties of recombinant spider silk coatings on orthopedic metal implants, specifically targeting the prevention of biofilm-related implant infections caused by multidrug-resistant bacteria such as Staphylococcus aureus. Utilizing Galleria mellonella as an in vivo model, stainless steel and titanium implants coated with films made of three different recombinant spider silk proteins are analyzed concerning biofilm formation and its impact on animal survival. Amongst the tested spider silk variants, the polyanionic eADF4(C16) demonstrates superior bacterial-repellent properties and improved larval survivability. Scanning electron microscopy analysis reveals reduced bacterial presence on eADF4(C16)-coated wires compared to uncoated controls, correlating with survival data. Based on the results, the potential of recombinant spider silk coatings to enhance implant functionality and longevity is highlighted, presenting a novel solution to combat biofilm-related implant infections and address the growing threat of antimicrobial resistance. Furthermore, employing Galleria mellonella as an in vivo model underscores a commitment to ethical research practices in studying biofilm infections.

一些蜘蛛丝基材料的微生物驱避性使它们成为生物医学应用的有趣候选者。本研究研究了重组蜘蛛丝涂层在骨科金属种植体上的微生物驱避特性,专门针对金黄色葡萄球菌等多重耐药细菌引起的生物膜相关种植体感染进行预防。以粗孔线虫为体内模型,对三种不同重组蜘蛛丝蛋白制成的膜包覆不锈钢和钛植入物的生物膜形成及其对动物生存的影响进行了分析。在测试的蜘蛛丝变体中,聚阴离子eADF4(C16)表现出优越的驱菌性能和提高的幼虫存活率。扫描电镜分析显示,与未涂覆eADF4(C16)的对照组相比,涂覆eADF4(C16)的导线上细菌的存在减少,这与存活数据相关。基于这些结果,重组蜘蛛丝涂层在增强种植体功能和寿命方面的潜力被强调,为对抗与生物膜相关的种植体感染和解决日益增长的抗生素耐药性威胁提供了一种新的解决方案。此外,采用千层杆菌作为体内模型强调了对研究生物膜感染的伦理研究实践的承诺。
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引用次数: 0
MXene Nanoparticles: Orchestrating Spherioidogenesis for Targeted Osteogenic and Neurogenic Differentiation MXene纳米颗粒:定向成骨和神经分化的球状形成
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-09 DOI: 10.1002/anbr.202570031
Yoonjoo Kang, Hyeongtaek Park, Surim Shim, Gul Karima, Subeen Lee, Kisuk Yang, Hwan D. Kim

MXenes

MXenes, novel 2D materials, enhance cell adhesion and guide stem cell fate. In article 2400100, Kisuk Yang, Hwan D. Kim, and co-workers show MXenes promote rapid spheroid formation and differentiation of human stem cells in 3D microenvironments, advancing tissue regeneration in bone and nerve repair. These findings demonstrate MXenes’ potential to enhance spheroid growth and differentiation, offering valuable applications for tissue regeneration.

MXenes,新型二维材料,增强细胞粘附,引导干细胞命运。在文章2400100中,Kisuk Yang, Hwan D. Kim及其同事发现MXenes在3D微环境中促进人类干细胞的快速球形形成和分化,促进骨和神经修复中的组织再生。这些发现表明MXenes具有促进球体生长和分化的潜力,为组织再生提供了有价值的应用。
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引用次数: 0
Dynamic Steerable Patterning of Microscale Particles and Living Cells Using an Ultrasound-Phased Array 利用超声相控阵对微尺度颗粒和活细胞进行动态可转向图案化
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-26 DOI: 10.1002/anbr.202400172
Rick J. P. van Bergen, Bart G. W. Groenen, Daniëlle C. A. Duffhues, Richard G. P. Lopata, Carlijn V. C. Bouten, Hans-Martin Schwab

Acoustic patterning is a noncontact method to manipulate the spatial distribution of small particles using the forces generated in an ultrasound standing wave field. The technique has found applications in fields such as cell sorting, microfabrication, and tissue engineering. For tissue engineering, acoustic patterning enables remote cell and tissue manipulation, even in clinical settings. Conventional axial patterning strategies rely on reflector-based or dual-probe approaches, limiting their application to controlled setups incompatible with in vivo conditions. In contrast, single-sided lateral patterning approaches, exploiting the transmit beamforming capabilities and tunability of a clinical ultrasound transducer array, can bridge the gap to in vivo applications. For the first time, a clinical-phased array is used to acoustically pattern microscale particles in both axial and lateral directions, with dynamic control over pattern shape and orientation by adjusting electronic transducer delays. The data are used to validate a numerical model designed to predict acoustic forces and particle displacement in current and future experiments. Finally, acoustic patterning is successfully applied to living cells, demonstrating the potential translation of the proof of concept toward living tissues. In conclusion, clinical transducer arrays can pattern particles and living cells, augmenting patterning flexibility and advancing acoustic patterning for tissue engineering.

声学图案化是一种非接触式方法,利用超声驻波场产生的力来操纵小颗粒的空间分布。该技术已应用于细胞分拣、微细加工和组织工程等领域。在组织工程方面,声学图案化可实现远程细胞和组织操作,甚至在临床环境中也是如此。传统的轴向图案化策略依赖于基于反射器或双探针的方法,限制了其在与体内条件不相容的受控设置中的应用。相比之下,利用临床超声换能器阵列的发射波束成形能力和可调谐性的单侧横向图案化方法,可以弥补体内应用的差距。这是首次使用临床相控阵对微米级粒子进行轴向和侧向声学图案化,并通过调整电子换能器延迟对图案形状和方向进行动态控制。这些数据用于验证一个数值模型,该模型旨在预测当前和未来实验中的声力和粒子位移。最后,声学图案设计成功应用于活细胞,证明了将概念验证转化为活组织的潜力。总之,临床换能器阵列可以对颗粒和活细胞进行图案化,提高了图案化的灵活性,推动了组织工程中的声学图案化。
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引用次数: 0
Polyurethane Nanocapsules Incorporating Epigallocatechin Gallate, A Green Tea Extract 含有没食子儿茶素没食子酸酯的聚氨酯纳米胶囊,一种绿茶提取物
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-26 DOI: 10.1002/anbr.202400204
Temitope Ale, Nhyira Ghunney, Narendra Pandala, Budd Tucker, Kassandra McFadden, Jack Hutcheson, Erin Lavik

Explosions cause 79% of combat-related injuries, often leading to traumatic brain injury (TBI) and hemorrhage. Epigallocatechin gallate (EGCG), a green tea polyphenol, aids neuroprotection and wound healing. In this work, we sought to investigate the fabrication and characterization of polyurethane nanocapsules encapsulating EGCG, demonstrating controlled, on-demand release, and highlighting their potential for targeted therapeutic delivery in trauma care.

爆炸导致79%的战斗相关伤害,通常导致创伤性脑损伤(TBI)和出血。表没食子儿茶素没食子酸酯(EGCG)是一种绿茶多酚,有助于神经保护和伤口愈合。在这项工作中,我们试图研究包封EGCG的聚氨酯纳米胶囊的制造和表征,证明控制,按需释放,并强调其在创伤护理中靶向治疗递送的潜力。
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引用次数: 0
Functional Silver-Loaded Porous Composite Scaffold for Bone Tissue Bacterial Infection 用于骨组织细菌感染的功能性载银多孔复合材料支架
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-21 DOI: 10.1002/anbr.202500004
An'nan Hu, Jian Zhou

Chronic osteomyelitis poses a significant clinical challenge in orthopedic care, contributing to substantial socioeconomic burdens. To address this issue, we engineered three-dimensional porous gelatin/β-tricalcium phosphate (β-TCP) composite scaffolds incorporating silver nanoparticles (AgNPs), designed to combine antimicrobial efficacy with osteoconductive potential. The AgNP-loaded scaffolds were synthesized and characterized. Biocompatibility and antibacterial activity were systematically evaluated. Results indicated that AgNP incorporation preserved the scaffolds’ interconnected porous architecture while improving hydrophilicity, water absorption capacity, and mechanical resilience. Cell counting kit-8 (CCK-8) assays revealed no statistically significant inhibition of cell proliferation relative to AgNP-free controls (P > 0.05), with scanning electron microscopy confirming robust cellular adhesion and proliferation. Osteogenic marker expression was markedly elevated in composite scaffolds compared to controls, with these enhancements remaining unaffected by optimal AgNP loading. Sustained Ag+ ion release persisted for six weeks, correlating with prolonged antibacterial efficacy against common pathogens. Collectively, the AgNP-loaded gelatin/β-TCP scaffolds demonstrated synergistic antibacterial activity, cytocompatibility, and osteogenic promotion. These properties position the composite as a promising biomaterial for addressing infection-related bone defects, offering a dual therapeutic strategy to mitigate microbial colonization while supporting tissue regeneration.

慢性骨髓炎在骨科护理中是一个重大的临床挑战,造成了巨大的社会经济负担。为了解决这个问题,我们设计了含有银纳米粒子(AgNPs)的三维多孔明胶/β-磷酸三钙(β-TCP)复合支架,旨在将抗菌功效与骨传导潜能结合起来。合成了负载agnp的支架并对其进行了表征。系统评价其生物相容性和抗菌活性。结果表明,AgNP的掺入保留了支架相互连接的多孔结构,同时提高了支架的亲水性、吸水能力和机械弹性。细胞计数试剂盒-8 (CCK-8)检测显示,与不含agnp的对照组相比,agnp对细胞增殖的抑制无统计学意义(P > 0.05),扫描电镜证实细胞粘附和增殖强劲。与对照组相比,复合支架中的成骨标志物表达明显升高,这些增强不受最佳AgNP负载的影响。Ag+离子的持续释放持续了6周,这与对常见病原体的抗菌效果延长有关。总的来说,agnp负载的明胶/β-TCP支架具有协同抗菌活性,细胞相容性和成骨促进作用。这些特性使复合材料成为解决感染相关骨缺损的有前途的生物材料,提供双重治疗策略,以减轻微生物定植,同时支持组织再生。
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引用次数: 0
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