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Formation of aggregated neutrophil extracellular traps in tissues is determining the efficacy of particulate nanoadjuvants 组织中聚集的中性粒细胞胞外陷阱的形成决定了颗粒纳米佐剂的功效
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-28 DOI: 10.1016/j.nano.2024.102798
Galyna Bila PhD , Valentyn Utka , Roman Grytsko Dr , Volodymyr Vovk Dr , Rostyslav Bilyy Dr, Prof.
Neutrophils are essential for innate immunity, using mechanisms like Neutrophil Extracellular Trap (NET) formation to fight pathogens. Aggregated NETs (aggNETs) help resolve inflammation by cleaving pro-inflammatory cytokines, while scattered NETs can exacerbate inflammation, leading to tissue damage. Co-injection of 10 nm nanodiamonds (ND10) with peptide antigens boosts immune responses, including anti-SARS-CoV-2 immunity, due to transient immune responses induced by aggNETs around ND10 particles. Diamond nanoparticles in adjuvant mixtures enhance vaccines, though the optimal dose is uncertain. Our study aimed to find the minimal ND10 amount needed for effective aggNETs formation and a robust immune response with minimal long-term tissue damage. In vivo experiments revealed 1 mg of ND10 per injection significantly enhances immune responses, forming granulomas rich in neutrophil elastase. Lower doses left scattered nanoparticles, insufficient for aggNETs formation. The effective ND10 dose for mice, 1 mg per injection, can be extrapolated to other organisms.
中性粒细胞对先天免疫至关重要,利用中性粒细胞胞外陷阱(NET)的形成等机制来对抗病原体。聚集的NETs (aggNETs)通过分裂促炎细胞因子帮助缓解炎症,而分散的NETs会加剧炎症,导致组织损伤。10纳米纳米金刚石(ND10)与肽抗原共同注射可增强免疫反应,包括抗sars - cov -2免疫,这是由于ND10颗粒周围的agnets诱导的短暂免疫反应。佐剂混合物中的金刚石纳米颗粒可增强疫苗,但最佳剂量尚不确定。我们的研究旨在找到有效形成agnets所需的最小ND10量和最小的长期组织损伤的强大免疫反应。体内实验显示,每次注射1mg ND10可显著增强免疫反应,形成富含中性粒细胞弹性酶的肉芽肿。较低的剂量会留下分散的纳米颗粒,不足以形成agnets。每次注射1毫克的ND10对小鼠的有效剂量可以推断到其他生物体。
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引用次数: 0
The nanocrystal-loaded liposome of tanshinone IIA with high drug loading and stability towards efficient liver fibrosis reversion 纳米晶载丹参酮IIA脂质体具有高载药量和稳定性,可有效逆转肝纤维化
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-27 DOI: 10.1016/j.nano.2024.102797
Chunyan Cai BS , Kai Liu MMed , Dejun Yang BS , Jijiao Wu BS , Zhaolei Peng BS , Yulin Wang BS , Jingjing Xi BS , Fan Xie MMed , Xiaofang Li Ph.D
Tanshinone IIA (TSIIA) is a lipid-soluble pharmacological constituent extracted from the Salvia miltiorrhiza with anti-hepatic fibrosis properties. However, its clinical use has been limited due to its poor water solubility and oral bioavailability. In this paper, we constructed a drug delivery system consisting of a drug nanocrystal core and a liposome shell: TSIIA nanocrystals@liposome (TNC@Lipo). This combination can greatly improve the solubility and bioavailability of poorly water-soluble drugs. TNC@Lipo was prepared by ultrasonic method combined with antisolvent method. In order to obtain the optimal TNC, we optimized the formulation ratio and preparation process of TNC by single-factor experiments. The results showed that TNC@Lipo had higher drug loading (27.86 ± 1.55 %) and superior stability. And TNC@Lipo can significantly reversed CCl4-induced liver fibrosis in mice compared with free-TSIIA. In conclusion, this study provides a new approach for the clinical application of TSIIA.
丹参酮IIA (TSIIA)是从丹参中提取的一种具有抗肝纤维化特性的脂溶性药理成分。然而,由于其水溶性和口服生物利用度差,其临床应用受到限制。在本文中,我们构建了一个由药物纳米晶核和脂质体壳组成的药物传递系统:TSIIA nanocrystals@liposome (TNC@Lipo)。这种组合可以大大提高水溶性差的药物的溶解度和生物利用度。用超声波法结合抗溶剂法制备了TNC@Lipo。为了获得最佳的TNC,我们通过单因素实验优化了TNC的配方配比和制备工艺。结果表明,TNC@Lipo具有较高的载药量(27.86±1.55%)和较好的稳定性。与游离tsiia相比,TNC@Lipo能显著逆转ccl4诱导的小鼠肝纤维化。本研究为TSIIA的临床应用提供了新的途径。
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引用次数: 0
Hyaluronic acid based nanoparticles that mediate sustained thanatin release protect against NDM-1–resistant bacterial infections in a murine model 在小鼠模型中,基于透明质酸的纳米颗粒介导持续的thanatin释放,可防止ndm -1耐药细菌感染。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-27 DOI: 10.1016/j.nano.2024.102796
Xiaojun Deng PhD , HaiBo Wang PhD , Chao Fang PhD , Min Xu BS , Zhufei Chu BS , Miaomiao Li BS , Zheng Hou PhD , Hongyan Qin PhD
Thanatin, a potent cationic antimicrobial peptide, has demonstrated remarkable efficacy against new NDM-1 producing bacteria. However, its clinical application is hampered by suboptimal stability in circulation and limited bioavailability in the human body. To overcome these challenges, a novel thanatin nanomedicine has been developed, which encapsulated thanatin in nanoparticles formed by electrostatic interactions between negatively charged HA and PLGA. The obtained ThaNPs demonstrated good stability, low cytotoxicity, and good metabolic ratio. ThaNPs significantly improve the stability of thanatin in the circulation, increasing its half-life in 50 % serum from 0.6 h to 3.2 h. Notably, the protective effect of ThaNPs against sepsis induced by NDM-1–producing Escherichia coli. was 10-fold higher than that of unencapsulated thanatin. These findings suggest that hyaluronic acid-based nanoparticles have the potentiality to overcome the clinical limitations associated with cationic antimicrobial peptides, thereby providing a novel and effective strategy for treating severe infections caused by antibiotic-resistant bacteria.
Thanatin是一种有效的阳离子抗菌肽,对新型NDM-1产生菌具有显著的抑制作用。然而,其临床应用受到循环稳定性欠佳和人体生物利用度有限的阻碍。为了克服这些挑战,一种新型的thanatin纳米药物已经被开发出来,该药物将thanatin包裹在由带负电荷的HA和PLGA之间的静电相互作用形成的纳米颗粒中。所得ThaNPs稳定性好,细胞毒性低,代谢率好。ThaNPs显著提高了thanatin在循环中的稳定性,使其在50% %血清中的半衰期从0.6 h增加到3.2 h。值得注意的是,ThaNPs对产生ndm -1的大肠杆菌引起的脓毒症具有保护作用。比未包封的大麻素高10倍。这些发现表明,基于透明质酸的纳米颗粒有可能克服与阳离子抗菌肽相关的临床局限性,从而为治疗抗生素耐药菌引起的严重感染提供一种新的有效策略。
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引用次数: 0
Comparison of cholesterol transport capacity of peptide- and polymer-based lipid Nanodiscs 多肽和聚合物脂质纳米盘胆固醇转运能力的比较
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-16 DOI: 10.1016/j.nano.2024.102795
Minzhi Yu PhD, Saatvik Vaishnav BS, Kristen Hong Dorsey PhD, May Thazin Phoo BSE, Antonela Rodriguez BS, Anna Schwendeman PhD
Apolipoprotein-based, synthetic high-density lipoprotein (sHDL) nanodiscs have been extensively studied as a potential therapeutic agent for cardiovascular disease due to their ability to promote reverse cholesterol transport. Recently, polymer-based nanodiscs have been made possible with the development of novel polymeric materials such as styrene-maleic anhydride copolymer (SMA). While the polymer-based nanodiscs resemble the discoidal structure of sHDLs, their functional similarity with sHDL has not been investigated. In the present study, we compared the SMA-based and peptide-based sHDL nanodiscs focusing on their cholesterol mobilization effects. Results showed that SMA-based nanoparticles presented similar particle size and in vitro cholesterol efflux effect to those of sHDL nanodiscs. However, SMA nanodiscs induced less cholesterol mobilization in vivo, possibly due to insufficient cholesterol esterification by lecithin:cholesterol acyltransferase.
以载脂蛋白为基础的合成高密度脂蛋白(sHDL)纳米盘因其促进胆固醇逆向运输的能力,已作为心血管疾病的潜在治疗药物被广泛研究。最近,随着苯乙烯-马来酸酐共聚物(SMA)等新型聚合物材料的开发,以聚合物为基础的纳米盘成为可能。虽然聚合物基纳米盘与 sHDL 的盘状结构相似,但它们与 sHDL 的功能相似性尚未得到研究。在本研究中,我们比较了基于 SMA 和基于肽的 sHDL 纳米盘,重点研究了它们的胆固醇动员效应。结果表明,基于 SMA 的纳米颗粒与基于 sHDL 的纳米微粒具有相似的粒径和体外胆固醇外排效果。然而,SMA 纳米微粒在体内诱导的胆固醇迁移率较低,这可能是由于卵磷脂:胆固醇酰基转移酶对胆固醇的酯化作用不足。
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引用次数: 0
Retraction notice to “In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies” [Nanomedicine: Nanotechnology, Biology and Medicine 10/1 (2014) 225–234] 用于神经修复疗法的磁化内皮祖细胞的体外血管生成性能和体内脑靶向》[Nanomedicine: Nanotechnology, Biology and Medicine 10/1 (2014) 225-234]的撤稿通知。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-19 DOI: 10.1016/j.nano.2024.102793
Elisa Carenza MSc , Verónica Barceló , Anna Morancho MSc , Lisa Levander MSc , Cristina Boada , Anna Laromaine PhD , Anna Roig PhD , Joan Montaner MD, PhD , Anna Rosell PhD
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引用次数: 0
Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a 通过激活 FOXO3a 使微胶囊姜黄醇用于卵巢癌的维持治疗。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 DOI: 10.1016/j.nano.2024.102789
Jing Wang PhD, MD , Bing Chen MSc , Jiezhen Yang MSc , Qin Tang MSc , Yan Zhong MSc , Jiyu Du MSc , Sheng Wang MSc , Qiang Wu PhD, MD , Yang Lu PhD , Yonghong Song PhD
Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC50 values of MC in two kinds of OC cells were 37.69 ± 2.43 and 28.54 ± 1.58 μg/mL, respectively. Mechanistically, curcumol could interact with the AKTThr308 site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.
卵巢癌(OC)的维持治疗(MT)对于防止疾病复发至关重要。姜黄醇具有有效的抗卵巢癌能力,且对正常卵巢上皮细胞毒性低,但其生物利用度较低。本文制备了胶束载体姜黄醇(MC),并对其在卵巢癌细胞上的抗肿瘤能力进行了研究。结果表明,MC 在两种 OC 细胞中的 IC50 值分别为 37.69 ± 2.43 和 28.54 ± 1.58 μg/mL。从机理上讲,姜黄醇可与AKTThr308位点相互作用,抑制FOXO3a的磷酸化,从而促进FOXO3a的核定位,并将其招募到PERK启动子上,激活ERS诱导的细胞凋亡途径。此外,MC还能抑制肿瘤裸鼠SKOV3细胞的生长,且DiR标记的MC能在肿瘤区域快速聚集。基于天然产物活性成分的纳米平台,MC为实现OC的高效MT提供了极大的可行性。
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引用次数: 0
Conceptual rationale for the use of chemically modified nanocomposites for active influence on atherosclerosis using the greater omentum model of experimental animals 利用化学修饰纳米复合材料对实验动物大网膜模型的动脉粥样硬化产生积极影响的概念原理。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-27 DOI: 10.1016/j.nano.2024.102787
Shamil Akhmedov PhD, MD , Ivan Stepanov MD , Sergey Afanasyev PhD, MD , Sergei Tverdokhlebov PhD , Victor Filimonov PhD , Nikolay Kamenshchikov MD , Anatoly Yermakov PhD , Suowen Xu PhD , Natalia Afanasyeva MD , Boris Kozlov PhD, MD
The use of chemically modified nanocomposites for atherosclerotic plaques can open up new opportunities for studying their effect on changing the structure of the plaque itself. It was shown on the model of the greater omentum of two groups of experimental animals (rats n = 30), which were implanted with Fe@C NPs nanocomposites of 10–30 Nm size into the omentum area. Group 1 (n = 15) consisted of animals that were implanted with chemically modified Fe@C NPs nanocomposites and control group 2 (n = 15) was with non-modified Fe@C NPs nanocomposites. After 1, 2 and 3 weeks we conducted the morphological study of changes in the structure of the omentum using two dyes (Nile Blue and Sudan III), which are specific for adipose tissue. Chemically modified nanocomposites have demonstrated, in contrast to non-modified nanoparticles, to cause morphological changes in the structure of the greater omentum accompanied by the probable release of a similar antiatherogenic factor.
将化学修饰纳米复合材料用于动脉粥样硬化斑块可为研究其对改变斑块本身结构的影响提供新的机会。实验显示,在两组实验动物(大鼠,n = 30)的大网膜模型中,将尺寸为 10-30 Nm 的 Fe@C NPs 纳米复合材料植入大网膜区域。第 1 组(n = 15)的动物被植入化学改性的 Fe@C 纳米复合材料,第 2 组(n = 15)的动物被植入非改性的 Fe@C 纳米复合材料。1周、2周和3周后,我们使用两种针对脂肪组织的染料(尼罗蓝和苏丹Ⅲ)对网膜结构的变化进行了形态学研究。与未经改性的纳米颗粒相比,经化学改性的纳米复合材料已被证明可引起大网膜结构的形态学变化,并可能释放出类似的抗动脉粥样硬化因子。
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引用次数: 0
Preparation of cubic liquid crystal nanoparticles of puerarin and its protective effect on ischemic stroke 葛根素立方液晶纳米颗粒的制备及其对缺血性中风的保护作用
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-27 DOI: 10.1016/j.nano.2024.102786
Jingbao Chen MD , Yuhang Xu MD , Yue Liu MD , Yun Meng MD , Long Wu MD , Wenxuan Cao MD , Dayuan Jiang MD , Xiaoqin Chu PhD
The low oral bioavailability of puerarin (Pur) affects its efficacy. Preparation of puerarin cubic liquid crystal nanoparticles (Pur-Cub) enhances the protective effect of Pur against ischemic stroke (IS) by increasing its bioavailability. The average particle size, PDI, and zeta potential of Pur-Cub were 274.70 ± 16.20 nm, 0.24 ± 0.05 and −25.30 ± 2.34 mV, respectively. Polarized light microscopy (PLM) and Small angle X-ray diffraction (SAXS) identified Pur-Cub as a cubic phase (Pn3m). The in vitro release of Pur-Cub was fast and then slow, in accordance with the biphasic kinetic equation. Pur-Cub increased the penetration of Pur in the intestine (mainly the duodenum) and significantly improved the bioavailability of Pur in the blood (304.16 %) and its distribution in the brain (1.69-fold) compared to Pur suspension. Pur-Cub narrowed down cerebral infarcts and significantly reduced levels of TNF-α, IL-1β, and IL-6 in a rat model of middle cerebral artery occlusion (MCAO).
葛根素(Pur)的口服生物利用度较低,影响了其药效。制备葛根素立方液晶纳米颗粒(Pur-Cub)可提高葛根素的生物利用度,从而增强其对缺血性中风(IS)的保护作用。Pur-Cub 的平均粒径、PDI 和 zeta 电位分别为 274.70 ± 16.20 nm、0.24 ± 0.05 和 -25.30 ± 2.34 mV。偏光显微镜(PLM)和小角 X 射线衍射(SAXS)确定 Pur-Cub 为立方相(Pn3m)。Pur-Cub 的体外释放先快后慢,符合双相动力学方程。与 Pur 悬浮液相比,Pur-Cub 增加了 Pur 在肠道(主要是十二指肠)中的渗透性,并显著提高了 Pur 在血液中的生物利用度(304.16%)及其在大脑中的分布(1.69 倍)。在大脑中动脉闭塞(MCAO)大鼠模型中,Pur-Cub缩小了脑梗塞的范围,并显著降低了TNF-α、IL-1β和IL-6的水平。
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引用次数: 0
Determination of spectroscopy marker of atherosclerotic carotid stenosis using FTIR-ATR combined with machine learning and chemometrics analyses 利用傅立叶变换红外-ATR 结合机器学习和化学计量学分析确定动脉粥样硬化性颈动脉狭窄的光谱标记。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-26 DOI: 10.1016/j.nano.2024.102788
Jan Jakub Kęsik PhD , Wiesław Paja PhD , Pawel Jakubczyk Prof. , Maryna Khalavka PhD , Piotr Terlecki Prof. , Marek Iłżecki PhD. , Wioletta Rzad MSc , Joanna Depciuch PhD
Atherosclerotic carotid stenosis (ACS) is a recognized risk factor for ischemic stroke. Currently, the gold diagnostic standard is Doppler ultrasound, the results of which do not provide certainty whether a given person should be qualified for surgery or not, because in some patients, carotid artery stenosis, for example at the level of 70 %, does not cause ischemic stroke in others yes. Therefore, there is a need for new methods that will clearly indicate the marker qualifying the patient for surgery. In this article we used Fourier Transform InfraRed Attenuated Total Reflectance (FTIR-ATR) spectra of serum collected from healthy and patients suffering from ACS, which had surgery were analyzed by machine learning and Principal Component Analysis (PCA) to determine chemical differences and spectroscopy marker of ACS. PCA demonstrated clearly differentiation between serum collected from healthy and non-healthy patients. Obtained results showed that in serum collected from ACS patients, higher absorbances of PO2− stretching symmetric, CH2 and CH3 symmetric and asymmetric and amide I vibrations were noticed than in control group. Moreover, lack of peak at 1106 cm−1 was observed in spectrum of serum from non-control group. As a result of spectral shifts analysis was found that the most important role in distinguishing between healthy and unhealthy patients is played by FTIR ranges caused by vibrations of PO2− phospholipids, amides III, II and CO lipid vibrations. Continuing, peaks at 1636 cm−1 and 2963 cm−1 were proposed as a potential spectroscopy markers of ACS. Finally, accuracy of obtained results higher than 90 % suggested, that FTIR-ATR can be used as an additional diagnostic tool in ACS qualifying for surgery.
动脉粥样硬化性颈动脉狭窄(ACS)是公认的缺血性中风的危险因素。目前,黄金诊断标准是多普勒超声检查,但其结果并不能确定某人是否符合手术条件,因为有些患者的颈动脉狭窄程度(例如 70%)不会导致缺血性中风,而有些患者的颈动脉狭窄程度(例如 70%)则会导致缺血性中风。因此,我们需要新的方法来明确指出患者是否符合手术条件。在本文中,我们使用傅立叶变换红外衰减全反射(FTIR-ATR)光谱分析了从健康人和接受过手术的 ACS 患者采集的血清,并通过机器学习和主成分分析(PCA)确定了 ACS 的化学差异和光谱标记。主成分分析清楚地显示了健康和非健康患者血清之间的差异。结果显示,与对照组相比,采集自 ACS 患者的血清中 PO2-对称伸展、CH2 和 CH3 对称和不对称以及酰胺 I 振动的吸光度更高。此外,在非对照组血清的光谱中没有发现 1106 cm-1 处的峰值。光谱移动分析结果表明,傅立叶变换红外光谱中,PO2-磷脂振动、酰胺 III、II 和 CO 脂质振动在区分健康和不健康患者中起着最重要的作用。此外,1636 cm-1 和 2963 cm-1 的峰值被认为是 ACS 的潜在光谱标记。最后,傅立叶变换红外-ATR 结果的准确率高于 90%,这表明傅立叶变换红外-ATR 可用作 ACS 手术资格的额外诊断工具。
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引用次数: 0
Enhanced osteointegration and osteogenesis of osteoblast cells by laser-induced surface modification of Ti implants 通过激光诱导对钛植入物进行表面改性,增强成骨细胞的骨整合和成骨作用。
IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-20 DOI: 10.1016/j.nano.2024.102785
Iaroslav Gnilitskyi PhD , Leonid Dolgov PhD , Aile Tamm PhD , Ana Maria Ferraria PhD , Kateryna Diedkova PhD , Sergei Kopanchuk PhD , Yaroslav Tsekhmister PhD , Santa Veiksina PhD , Vincent Polewczyk PhD , Maksym Pogorielov PhD
Dental and orthopedic implants have become routine medical technologies for tooth replacement and bone fixation. Despite significant progress in implantology, achieving sufficient osseointegration remains a challenge, often leading to implant failure over the long term. Nanotechnology offers the potential to mimic the natural patterns of living tissues, providing a promising platform for tissue engineering and implant surface design. Among the various methods for developing nanostructures, High-Regular Laser-Induced Periodic Surface Structures (HR-LIPSS) techniques stand out for their ability to fabricate highly ordered nanostructures with excellent long-range repeatability and production efficiency. In this study, we utilized an innovative technical approach to generate traditional laser-induced superficial LIPSS nanostructures, followed by detailed surface analysis using classical microscopy and physicochemical methods. Our findings demonstrate for the first time that nanostructured LIPSS surfaces can significantly enhance cell adhesion and proliferation while providing an optimal environment for cell metabolism. Given the high reproducibility, low cost, and potential of HR-LIPSS techniques to support cell growth and differentiation, this novel technology has the potential to impact both the industrial development of new implants and clinical outcomes after implantation.
牙科和骨科植入物已成为牙齿替换和骨固定的常规医疗技术。尽管种植学取得了重大进展,但实现充分的骨结合仍然是一项挑战,往往会导致种植体长期失效。纳米技术具有模仿活组织自然形态的潜力,为组织工程和种植体表面设计提供了一个前景广阔的平台。在开发纳米结构的各种方法中,高规则激光诱导周期表面结构(HR-LIPSS)技术因其能够制造出高度有序的纳米结构、出色的长程可重复性和生产效率而脱颖而出。在这项研究中,我们采用了一种创新的技术方法来生成传统的激光诱导表层 LIPSS 纳米结构,然后使用经典的显微镜和物理化学方法进行了详细的表面分析。我们的研究结果首次证明,LIPSS 纳米结构表面能显著增强细胞粘附和增殖,同时为细胞代谢提供最佳环境。鉴于 HR-LIPSS 技术的高可重复性、低成本和支持细胞生长和分化的潜力,这项新技术有可能对新型植入物的工业开发和植入后的临床效果产生影响。
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