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Development of a dextrin-vitamin D3 micelle nanocarrier for the antimicrobial peptide LLKKK18 as a potential therapeutic agent for bone infections. 开发抗菌肽 LLKKK18 的糊精-维生素 D3 胶束纳米载体,作为骨感染的潜在治疗剂。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb00903g
Alexandra Machado, Miguel Gama, José Alberto Martins

In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against S. aureus, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.

在这项研究中,我们开发了一种抗菌肽 LL18 自组装胶束载体的快速合成方法。糊精与琥珀酰化维生素 D3 和琥珀酸酐进行共价单锅官能化,产生了一种两亲性材料,它能在水介质中自组装成胶束。琥珀酸化糊精-维生素 D3 胶束通过静电和疏水相互作用有效地负载了 LL18。值得注意的是,负载 LL18 的胶束制剂大大提高了游离 LL18 对金黄色葡萄球菌的抗菌活性,彻底消除了其严重的溶血活性,使 LL18 从成骨细胞核周区内化到溶酶体,并降低了对成骨细胞和巨噬细胞的细胞毒性。总之,这项研究表明,基于糊精、维生素 D3 和抗菌肽的自组装胶束制剂是开发不依赖抗生素、不易产生细菌耐药性的多功能抗菌剂的理想平台,可用于治疗骨感染。
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引用次数: 0
Design and characterization of β-tricalcium phosphate-based self-passivating coatings on magnesium alloys. 基于β-磷酸三钙的镁合金自钝化涂层的设计与表征
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01214c
Erdem Şahin, Roberta Ruggiero, Marco Tatullo, Francesco Paduano, Meltem Alp, Ahmed Şeref

Background: Magnesium alloys degrade rapidly in salt solutions, which limits their use without passivating treatments. AZ31 alloy is particularly promising for implant applications owing to its biodegradability and mechanical properties, necessitating effective corrosion-resistant coatings. Aim: In this study, a self-passivating reactive coating was designed and evaluated for AZ31 magnesium alloy plates using β-tricalcium phosphate (TCP) to enhance corrosion resistance and biocompatibility. Methods: Solutions of TCP, trisodium citrate, magnesium nitrate, hydroxyethyl cellulose (HEC), and sodium chloride were used to dip-coat AZ31 plates. The coated samples were immersed in 3.5 wt% NaCl solution. Phase evolution was analysed using gravimetry, X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). The biological response of the coated samples was evaluated through MTT and resazurin assays. Results: The coating formed a stable TCP/HEC layer that gradually dissolved over two weeks, converting the surface to magnesium hydroxide, magnesium oxychloride, and magnesium phosphate phases. The formation of brucite, responsible for passivation in the long term, was observed. The coating effectively prevented excessive magnesium oxychloride formation and stabilised magnesium hydroxide after one week. Biological characterization indicated that the coating on AZ31 is safe on the Saos-2 and L929 cell lines. Conclusion: The TCP-based coating enhances the corrosion resistance of AZ31 alloy in salt solutions, promoting passivating phases and limiting corrosive products, thereby ameliorating biocompatibility issues. This coating demonstrates substantial potential for extending the longevity and functionality of magnesium alloy implants.

背景:镁合金在盐溶液中会迅速降解,如果不进行钝化处理,就会限制其使用。AZ31 合金因其生物可降解性和机械性能,在植入应用中尤其具有前景,因此需要有效的抗腐蚀涂层。目的:在本研究中,设计并评估了一种自钝化反应涂层,该涂层用于 AZ31 镁合金板材,使用了 β-磷酸三钙 (TCP),以增强其耐腐蚀性和生物相容性。方法:使用 TCP、柠檬酸三钠、硝酸镁、羟乙基纤维素(HEC)和氯化钠溶液对 AZ31 板材进行浸涂。将涂层样品浸入 3.5 wt% 的氯化钠溶液中。使用比重计、X 射线衍射(XRD)、能量色散 X 射线(EDX)光谱和扫描电子显微镜(SEM)分析了相变。涂覆样品的生物反应通过 MTT 和resazurin 试验进行了评估。结果显示涂层形成了稳定的 TCP/HEC 层,该层在两周内逐渐溶解,将表面转化为氢氧化镁、氧氯化镁和磷酸镁相。观察到了青金石的形成,它对长期钝化起着重要作用。一周后,涂层有效地防止了氧氯化镁的过度形成,并稳定了氢氧化镁。生物表征表明,AZ31 涂层对 Saos-2 和 L929 细胞系是安全的。结论:基于 TCP 的涂层增强了 AZ31 合金在盐溶液中的耐腐蚀性,促进了钝化相,限制了腐蚀产物,从而改善了生物相容性问题。这种涂层在延长镁合金植入物的寿命和功能方面具有很大的潜力。
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引用次数: 0
Reconfiguring the endogenous electric field of a wound through a conductive hydrogel for effective exudate management to enhance skin wound healing. 通过导电水凝胶重新配置伤口的内生电场,有效管理渗出物,促进皮肤伤口愈合。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01349b
Yukun Yan, Yuanyuan Chen, Hanqing Dai, Wanlu Zhang, Ruiqian Guo

The ionic environment has a strong influence on the bioelectricity of skin, which is also present in the wound healing process. Inspired by this, we proposed a mechanism for hydrogel-based dressings to respond to endogenous electric fields through exudate absorption and conducted a verification study using a typical hydrogel, namely, polyacrylamide and sodium alginate (PAM-SA) hydrogels, as an example. Theoretical calculations showed that the PAM-SA hydrogels could absorb and orient the various electrolytes of exudate in the hydrogel at the wound site, contributing to the reconstruction of the electric field at the wound site. During the treatment process, this effect significantly accelerated the healing process of the rat epidermis, which exceeded the conventional dressing in terms of healing speed and efficacy, and the wounds on the complete layer of rat skin (wound area: 1.13 cm2) could be rapidly repaired within 10 days. Revealing the electrophysiological behavior of PAM-SA dressings during wound healing can help further improve the design model, the optimization concept, and development paths for the bioelectrical structures of modern dressings and bioelectrical stimulation in wound healing.

离子环境对皮肤的生物电有很大的影响,这同样存在于伤口愈合过程中。受此启发,我们提出了水凝胶敷料通过吸收渗出液响应内生电场的机制,并以聚丙烯酰胺和海藻酸钠(PAM-SA)水凝胶这一典型水凝胶为例进行了验证研究。理论计算表明,PAM-SA 水凝胶可以吸收伤口处水凝胶中的各种电解质并使其定向,从而促进伤口处电场的重建。在治疗过程中,这种效应明显加快了大鼠表皮的愈合过程,在愈合速度和疗效方面都超过了传统敷料,大鼠皮肤全层(伤口面积:1.13 平方厘米)上的伤口可在 10 天内迅速修复。揭示PAM-SA敷料在伤口愈合过程中的电生理行为,有助于进一步完善现代敷料的生物电结构和生物电刺激在伤口愈合中的应用的设计模型、优化理念和发展路径。
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引用次数: 0
Study on porous coral scaffolds containing a hydroxyapatite layer doped with selenium and their properties. 含掺硒羟基磷灰石层的多孔珊瑚支架及其性能研究
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01112k
Tianjing Bao, Jian Ren, Yiyuan Wu, Yang Cao, Haobo Pan, Chunlin Deng

The repair of bone defects caused by osteosarcoma is still a significant clinical issue, and new scaffolds need to be developed to solve this problem. The ocean is a treasure trove for developing new biomedical materials, and coral is widely thought to be suitable as a scaffold for bone implant materials due to its porous structure and mechanical properties. Selenium is known for its antioxidant and antitumor effects, inducing tumor cell cycle arrest. In this study, we hydrothermally transformed corals to grow a hydroxyapatite layer on the scaffold surface (CHAp) and combined it with selenium to obtain selenium-doped scaffolds (Se-CHAp) without affecting the porous structure of the coral. The research successfully validates their biocompatibility and the antitumor efficacy against 143B osteosarcoma cells. The results indicate that the Se-CHAp scaffolds yielded an obvious inhibitory effect on the proliferation of osteosarcoma cells, highlighting that they have huge prospects for application in biomedical technology.

骨肉瘤导致的骨缺损修复仍是一个重要的临床问题,需要开发新的支架来解决这一问题。海洋是开发新型生物医学材料的宝库,而珊瑚因其多孔结构和机械性能被广泛认为适合作为骨植入材料的支架。众所周知,硒具有抗氧化和抗肿瘤作用,能诱导肿瘤细胞周期停止。在这项研究中,我们对珊瑚进行水热转化,在支架表面生长出羟基磷灰石层(CHAp),并将其与硒结合,在不影响珊瑚多孔结构的情况下获得掺硒支架(Se-CHAp)。研究成功验证了其生物相容性和对 143B 骨肉瘤细胞的抗肿瘤功效。研究结果表明,Se-CHAp 支架对骨肉瘤细胞的增殖具有明显的抑制作用,在生物医学技术领域具有广阔的应用前景。
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引用次数: 0
A smart adaptable metal sequestering peptide conjugate to modulate Aβ fibrillar aggregation. 一种可调节 Aβ 纤维聚集的智能型金属螯合肽共轭物。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01093k
Tanmay Mondal, Sujan Kalita, Rinku Dutta, Bhubaneswar Mandal

The aggregation of amyloid β peptide (Aβ) in the presence of elevated levels of transition-metal ions, e.g., Fe3+, Cu2+, Zn2+, is accountable for enhanced cellular toxicity in Alzheimer's disease. Many strategies are reported to inhibit either Cu2+, Zn2+, or Fe3+-induced Aβ fibrillation, focused on one metal. Herein, a taurine-containing adaptable metal sequestering peptide (AMSP) has been developed as the modulator of any of the cited metal-induced Aβ-aggregation in vitro. We designed the peptide conjugate comprising VFFA as a recognition motif and a taurine moiety coupled with a pendant chain of glutamic acid such that the -SO3H groups of taurine lie nearby 13His and 14His of Aβ, and sequester such metal ions that construct the salt bridge preponderantly via13His-metal-14His composition as well as bridges with 6His of Aβ. We checked the modulation of fibrillar aggregates of Aβ in the presence of metal ions by monitoring the fibril accumulation using several biophysical methods. The results established that non-aggregating AMSP sequesters Zn2+ preferably, along with Fe3+ and Cu2+ ions from the metal-Aβ complex at the physiological condition, efficiently inhibiting Aβ aggregation. While such adaptable metal binders that can chelate various metals are new, AMSP inhibits aggregation through selective recognition and metal scavenging.

在过渡金属离子(如 Fe3+、Cu2+、Zn2+)水平升高的情况下,淀粉样β肽(Aβ)的聚集是阿尔茨海默病中细胞毒性增强的原因。据报道,许多抑制 Cu2+、Zn2+ 或 Fe3+诱导的 Aβ 纤维化的策略都集中在一种金属上。在此,我们开发了一种含牛磺酸的适应性金属封闭肽(AMSP),作为上述任何一种金属诱导的 Aβ 聚集的体外调节剂。我们设计了由 VFFA 作为识别基团、牛磺酸分子和谷氨酸悬链组成的多肽共轭物,使牛磺酸的 -SO3H 基团位于 Aβ 的 13His 和 14His 附近,并封存主要通过 13His - 金属 - 14His 构成盐桥以及与 Aβ 的 6His 搭桥的金属离子。我们使用多种生物物理方法监测了 Aβ 的纤维聚集,从而检测了金属离子存在时 Aβ 纤维聚集的调节情况。结果表明,在生理条件下,非聚合型 AMSP 与金属-Aβ 复合物中的 Fe3+ 和 Cu2+ 离子一起,可优先封存 Zn2+,从而有效抑制 Aβ 的聚合。虽然这种可螯合各种金属的适应性金属粘合剂是一种新产品,但 AMSP 可通过选择性识别和清除金属来抑制聚集。
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引用次数: 0
Photocaging of amino acids and short peptides by arylidenethiazoles: mechanism, photochemical characteristics and biological behaviour. 芳基亚噻唑对氨基酸和短肽的光致变色:机理、光化学特性和生物学行为。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01441c
Aleksey A Gagarin, Artem S Minin, Vadim A Shevyrin, Enrico Benassi, Nataliya P Belskaya

A series of fluorophores based on the (5-methyl-4-phenylthiazol-2-yl)-3-phenylacrylonitrile (MPTA) core were designed and synthesised for photocaging of amino acids and peptides. The photophysical characteristics of these compounds and their hybrids with biomolecules were thoroughly investigated through a joint experimental, spectral and computational approach. The photorelease ability of the obtained amino acids-MPTA and peptides-MPTA hybrids was studied under various conditions, including different UV irradiation wavelength and power, and solvents. The main reaction products were identified using high-performance liquid chromatography combined with high-resolution mass spectrometry. Photo uncaging kinetics was quantitatively studied using absorption spectroscopy. The mechanism of photorelease of amino acids and peptides was elucidated through quantum mechanical calculations, which were also used for the exploration of photophysical properties of the excited states, and photodissociation energetics quantification. Relationships between the structure of fluorophores and photodissociation characteristics were estimated, and fluorophores with the good uncaging characteristics (biomolecule photoreleasing yield, uncaging rate, and effectiveness) were identified. Cell viability assays using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT showed a low cytotoxicity of the hybrids. Confocal microscopy revealed the easy penetration of the hybrids into living cells and their selective accumulation in the endoplasmic reticulum, lipid droplets and mitochondria, depending on their chemical structure.

我们设计并合成了一系列以(5-甲基-4-苯基噻唑-2-基)-3-苯基丙烯腈(MPTA)为核心的荧光团,用于对氨基酸和肽进行光成像。通过联合实验、光谱和计算方法,对这些化合物及其与生物大分子的混合物的光物理特性进行了深入研究。在不同的紫外线照射波长、功率和溶剂等条件下,研究了所获得的氨基酸-MPTA 和肽-MPTA 混合物的光释放能力。采用高效液相色谱法和高分辨率质谱法对主要反应产物进行了鉴定。利用吸收光谱对光解笼动力学进行了定量研究。通过量子力学计算阐明了氨基酸和肽的光释放机理,还利用量子力学计算探索了激发态的光物理特性,并对光解离能进行了量化。估算了荧光团结构与光解离特性之间的关系,并确定了具有良好解笼特性(生物分子光释放产率、解笼率和有效性)的荧光团。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑或 MTT 进行的细胞活力检测显示,混合物的细胞毒性较低。共聚焦显微镜显示,混合物很容易渗透到活细胞中,并根据其化学结构的不同,选择性地积聚在内质网、脂滴和线粒体中。
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引用次数: 0
Expression of concern: Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer. 表达关切:二维碳化钛的表面修饰工程,用于乳腺癌的高效协同综合治疗。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb90175d
Lei Bai, Wenhui Yi, Taiyang Sun, Yilong Tian, Ping Zhang, Jinhai Si, Xun Hou, Jin Hou

Expression of concern for 'Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer' by Lei Bai et al., J. Mater. Chem. B, 2020, 8, 6402-6417, https://doi.org/10.1039/D0TB01084G.

对 Lei Bai 等人的 "Surface Modification Engineering of Two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer"(《二维碳化钛的表面修饰工程用于乳腺癌的高效协同多疗法》)表示关注,J. Mater.Chem.B,2020,8,6402-6417,https://doi.org/10.1039/D0TB01084G。
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引用次数: 0
ATP-responsive copper(II)-doped ZIF-nanoparticles for synergistic cancer therapy: combining cuproptosis and chemo/chemodynamic therapy. 用于癌症协同治疗的 ATP 响应型掺杂铜(II)的 ZIF 纳米粒子:结合杯突疗法和化疗/化学动力学疗法。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01574f
Wei-Qun Deng, Jun-Tao Chen, Si-Si Chen, Zhi-Qing Wang, Guo-Jiang Mao, Liufang Hu, Juan Ouyang, Chun-Yan Li

Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu2+-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu2+-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H2O2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu2+-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.

癌症是一项紧迫的全球健康挑战,其特点是发病快、死亡率高。传统的治疗方法不足以达到预期的治疗效果,因此迫切需要找到一种有效而安全的癌症治疗方法。在这项研究中,通过在 ZIF-90 中加入铜(II)(Cu(II))并封装多柔比星(DOX),设计出了一种称为 Cu2+-DOX@ZIF-90 的掺铜纳米粒子。Cu2+-DOX@ZIF-90 利用癌细胞中 ATP 水平高于正常细胞的特性,在细胞内进行降解,从而释放 DOX 和 Cu(II)。DOX 是一种传统的临床化疗药物,可诱导癌细胞凋亡。Cu(II)与谷胱甘肽(GSH)相互作用生成 Cu(I),催化 H2O2 生成˙OH,从而促使癌细胞凋亡。同时,GSH 的减少可增强化学动力疗法(CDT)的治疗效果。此外,Cu(II)还能引发脂酰化线粒体蛋白的聚集,导致 DLAT 寡聚体的形成,最终促进癌细胞的杯突变。体内实验结果表明,Cu2+-DOX@ZIF-90 不会对肿瘤小鼠的正常组织和器官造成损伤,肿瘤抑制率高达 86.18%。这种将化疗、CDT 和杯突症结合起来的协同方法为有效、安全地治疗癌症带来了巨大希望。
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引用次数: 0
The cyano positional isomerism strategy for constructing mitochondria-targeted AIEgens with type I reactive oxygen species generation capability. 利用氰基位置异构策略构建具有 I 型活性氧生成能力的线粒体靶向 AIEgens。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01847h
Jiabao Zhuang, Quan Pan, Chunli Zhou, Ziying Cai, Nan Li, Na Zhao

In this work, a series of cationic luminogens (designated as PSMP isomers) were developed based on the cyano positional isomerism strategy. The isomerism of the cyano substituent on the molecular skeleton can finely regulate the optical behaviour, the type of photoinduced reactive oxygen species (ROS), and mitochondria-targeted capability of isomers. Interestingly, PSMP-4, with the cyano group installed at an appropriate location, exhibits a special aggregation-induced emission effect and potent O2˙- generation efficacy through the type I photochemistry pathway. Notably, PSMP-4 can accumulate in mitochondria with high specificity. Taking advantage of its excellent photostability, PSMP-4 realizes in situ mitochondria imaging in a washing-free manner and sensitive response to the change of mitochondrial membrane potential. The integration of comprehensive photophysical properties and mitochondrial specificity enable PSMP-4 to successfully trigger the death of cancer cells through an efficient type I photodynamic therapy process both in vitro and in multicellular tumor spheroid models.

这项研究基于氰基位置异构策略开发了一系列阳离子发光剂(命名为 PSMP 异构体)。分子骨架上氰基取代基的异构可以精细调节异构体的光学行为、光诱导活性氧(ROS)的类型以及线粒体靶向能力。有趣的是,在适当位置加入氰基的 PSMP-4 通过 I 型光化学途径表现出特殊的聚集诱导发射效应和强效的 O2˙-生成功效。值得注意的是,PSMP-4 能以高度特异性积聚在线粒体中。利用其优异的光稳定性,PSMP-4 可以免清洗的方式实现线粒体原位成像,并对线粒体膜电位的变化做出灵敏反应。综合的光物理特性和线粒体特异性使 PSMP-4 能够在体外和多细胞肿瘤球体模型中通过高效的 I 型光动力疗法过程成功引发癌细胞死亡。
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引用次数: 0
Bioactive glass-polymer nanocomposites: a comprehensive review on unveiling their biomedical applications. 生物活性玻璃聚合物纳米复合材料:揭示其生物医学应用的全面综述。
Pub Date : 2024-11-13 DOI: 10.1039/d4tb01525h
Radhakrishnan Sreena, Gurusamy Raman, Geetha Manivasagam, A Joseph Nathanael

Most natural and synthetic polymers are promising materials for biomedical applications because of their biocompatibility, abundant availability, and biodegradability. Their properties can be tailored according to the intended application by fabricating composites with other polymers or ceramics. The incorporation of ceramic nanoparticles such as bioactive glass (BG) and hydroxyapatite aids in the improvement of mechanical and biological characteristics and alters the degradation kinetics of polymers. BG can be used in the form of nanoparticles, nanofibers, scaffolds, pastes, hydrogels, or coatings and is significantly employed in different applications. This biomaterial is highly preferred because of its excellent biocompatibility, bone-stimulating activity, and favourable mechanical and degradation characteristics. Different compositions of nano BG are incorporated into the polymer system and studied for positive results such as enhanced bioactivity, better cell adherence, and proliferation rate. This review summarizes the fabrication and the progress of natural/synthetic polymer-nano BG systems for biomedical applications such as drug delivery, wound healing, and tissue engineering. The challenges and the future perspectives of the composite system are also addressed.

大多数天然和合成聚合物都具有生物相容性、丰富的可获得性和生物降解性,因此是生物医学应用中很有前途的材料。通过与其他聚合物或陶瓷制成复合材料,可根据预期应用定制其特性。加入生物活性玻璃(BG)和羟基磷灰石等陶瓷纳米颗粒有助于改善聚合物的机械和生物特性,并改变聚合物的降解动力学。生物活性玻璃可以纳米颗粒、纳米纤维、支架、糊状物、水凝胶或涂层的形式使用,并广泛应用于不同领域。这种生物材料因其出色的生物相容性、骨刺激活性以及良好的机械和降解特性而备受青睐。在聚合物体系中加入不同成分的纳米 BG,可获得积极的效果,如增强生物活性、提高细胞附着力和增殖率。本综述总结了天然/合成聚合物-纳米 BG 系统在药物输送、伤口愈合和组织工程等生物医学应用领域的制造和进展情况。此外,还探讨了复合系统面临的挑战和未来展望。
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引用次数: 0
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