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Externally triggered drug delivery systems 外部触发给药系统
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.004

Externally triggered drug delivery systems empower patients or healthcare providers to utilize external stimuli to initiate drug release from implanted systems. This approach holds significant potential for clinical disease management, offering appealing features like enhanced patient adherence through the elimination of needles and medication reminders. Additionally, it facilitates personalized medicine by granting patients control over the timing, dosage, and duration of drug release. Moreover, it enables precise drug delivery to targeted locations where external stimuli are applied. Advances in materials science, nanotechnology, chemistry, and biology have been pivotal in driving the development of these systems. This review presents an overview of the progress in research on drug release systems responsive to external stimuli, such as light, ultrasound, magnetic fields, and temperature. It discusses the construction strategies of externally triggered drug delivery systems, the mechanisms governing triggered drug release, and their applications in disease management.

外部触发给药系统使患者或医疗服务提供者能够利用外部刺激来启动植入系统的药物释放。这种方法在临床疾病管理方面具有巨大的潜力,其吸引人的特点包括通过消除针头和用药提醒来提高患者的依从性。此外,它还能让患者控制药物释放的时间、剂量和持续时间,从而促进个性化医疗。此外,它还能将药物精确输送到施加外部刺激的目标位置。材料科学、纳米技术、化学和生物学的进步在推动这些系统的发展方面起到了关键作用。本综述概述了对光、超声波、磁场和温度等外部刺激做出反应的药物释放系统的研究进展。它讨论了外部触发给药系统的构建策略、触发药物释放的机制及其在疾病治疗中的应用。
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引用次数: 0
Magnesium-based bioceramic-enhanced composites fabricated via friction stir processing 通过搅拌摩擦加工制造镁基生物陶瓷增强复合材料
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.006

Improving the degradation performance and enhancing the biocompatibility are the main challenges of Mg-based biodegradable implants. In this study, a nano-hydroxyapatite-enhanced (nHA) Mg matrix composite was fabricated via friction stir processing and characterised, including microstructure, mechanical, in vitro degradation properties, and cytocompatibility. Hydroxyapatite is renowned for its superior bone compatibility, promoting healing responses and tissue growth. Friction stirring created a gradient grain structure in the alloy, with the stir zone exhibiting the highest grain refinement. The stir zone also contained most of the incorporated nHA and exhibited a strong texture with grains preferentially oriented along the [0001] direction. Immersion and polarisation experiments showed an increase in the FSPed WE43-nHA's corrosion resistance due to the refined microstructure. The treatment also caused a shift in the corrosion mode of the alloy from localized to uniform corrosion despite some localized corrosion associated with the nHA. Cytocompatibility tests in human osteoblast (HOB) cell lines indicated good biocompatibility in the Mg-nHA alloy, with cells exhibiting relatively healthy morphology and increased live cell count. Friction stir processing is a viable manufacturing option for creating Mg-based metal matrix composites with improved corrosion resistance and good biocompatibility.

改善降解性能和提高生物相容性是镁基可生物降解植入物面临的主要挑战。在这项研究中,通过搅拌摩擦加工制造了纳米羟基磷灰石增强(nHA)镁基复合材料,并对其进行了表征,包括微观结构、机械性能、体外降解性能和细胞相容性。羟基磷灰石因其卓越的骨兼容性、促进愈合反应和组织生长而闻名。摩擦搅拌在合金中形成了梯度晶粒结构,搅拌区的晶粒细化程度最高。搅拌区还含有大部分掺入的 nHA,并呈现出强烈的纹理,晶粒优先沿 [0001] 方向取向。浸泡和极化实验表明,由于微观结构的细化,FSPed WE43-nHA 的耐腐蚀性能有所提高。处理还导致合金的腐蚀模式从局部腐蚀转变为均匀腐蚀,尽管 nHA 存在一些局部腐蚀。人类成骨细胞(HOB)细胞系的细胞相容性测试表明,Mg-nHA 合金具有良好的生物相容性,细胞表现出相对健康的形态,活细胞数量增加。搅拌摩擦加工是制造具有更强耐腐蚀性和良好生物相容性的镁基金属基复合材料的可行方法。
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引用次数: 0
Advances of surface modification to alleviate oxidative stress-induced valve degeneration 表面改性在缓解氧化应激引起的瓣膜退化方面取得进展
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.003

Valvular heart disease (VHD) is a significant public health threat, with heart valve replacement surgery being the standard treatment for severe cases. Despite of advancements in artificial heart valves, their longevity remains limited due to in vivo degeneration. In consequence, there is an urgent need for effective methods to enhance the durability of artificial heart valves. Because oxidative stress (OS) is a key driving factor contributing to the failure of cardiovascular implants, this review focuses on how OS plays a critical role in heart valve degeneration, and its relationship with four major physiological mechanisms: extracellular matrix (ECM) degradation, immune response, thrombosis and lipid metabolism. By highlighting OS as a potential therapeutic target, we explore surface modification strategies that incorporate these fundamental mechanisms, refer to passive approaches including OS elimination, immunosuppression, blocking surface-degradation active groups, and anticoagulation, and active approaches such as regulating biological function recovery, and surface endothelial remodeling. These strategies aim to delay or reverse artificial valves degeneration via combining with the perspective of OS regulation, ultimately extending the prognosis period after heart valve replacement surgeries.

瓣膜性心脏病(VHD)是一种严重威胁公众健康的疾病,心脏瓣膜置换手术是治疗严重病例的标准方法。尽管人工心脏瓣膜技术不断进步,但由于体内退化,其寿命仍然有限。因此,迫切需要有效的方法来提高人工心脏瓣膜的耐用性。由于氧化应激(OS)是导致心血管植入物失效的一个关键驱动因素,本综述将重点探讨氧化应激如何在心脏瓣膜退化中发挥关键作用,以及它与细胞外基质(ECM)降解、免疫反应、血栓形成和脂质代谢这四大生理机制之间的关系。通过强调OS是潜在的治疗靶点,我们探讨了结合这些基本机制的表面修饰策略,包括消除OS、免疫抑制、阻断表面降解活性基团和抗凝等被动方法,以及调节生物功能恢复和表面内皮重塑等主动方法。这些策略旨在结合OS调节的观点,延缓或逆转人工瓣膜的退化,最终延长心脏瓣膜置换手术后的预后期。
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引用次数: 0
The state-of-the-art therapeutic paradigms against sepsis 最先进的败血症治疗范例
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.005

Sepsis frequently leads to life-threatening organ failure due to an in appropriate response by the body to bacterial, viral, and fungal infections. In recent years, there has been an increasing interest in using nanoparticles to develop biomarkers and drug delivery systems that have significantly improved the treatment of infectious diseases. Herein, we update the most recent development of nanoparticle-based therapeutics for sepsis treatment. This article begins with a brief overview of how sepsis is triggered and its associated diseases. It also explores the differences between traditional and modern treatment approaches. Afterward, the reasons for embracing nanotechnology-based therapies for sepsis are summarized, including their ability to reduce inflammation, provide antioxidant effects, regulate cell signaling pathways, manage reactive oxygen and nitrogen species (RONS) production, control autophagy and apoptosis, clear lipopolysaccharides (LPS) from the blood, inhibits the formation of cell-free DNA and cytokine storms. Furthermore, the special emphasis is on updating the use of nanotechnology-mediated drug delivery systems, such as nanoparticles, liposomes, and exosomes, in the treatment of sepsis caused by various microorganisms. Moreover, we also discuss polymer mediated therapy and some dynamic therapeutic aspects in septecemia disease. In addition, the article highlights the challenges and a limitation associated with using drug delivery for sepsis treatment and expresses the hope that this review will accelerate the development of more effective sepsis therapies and facilitate the transition from research to practical clinical application.

由于机体对细菌、病毒和真菌感染的反应不当,败血症经常导致危及生命的器官衰竭。近年来,人们对使用纳米粒子开发生物标记物和给药系统的兴趣与日俱增,这极大地改善了感染性疾病的治疗。在此,我们将介绍基于纳米粒子的败血症治疗方法的最新进展。本文首先简要概述了败血症的诱发原因及其相关疾病。文章还探讨了传统治疗方法与现代治疗方法之间的差异。随后,总结了采用基于纳米技术的败血症疗法的原因,包括它们能够减轻炎症、提供抗氧化效果、调节细胞信号通路、管理活性氧和氮物种(RONS)的产生、控制自噬和细胞凋亡、清除血液中的脂多糖(LPS)、抑制游离 DNA 的形成和细胞因子风暴。此外,我们还特别强调了纳米技术介导的给药系统(如纳米颗粒、脂质体和外泌体)在治疗由各种微生物引起的败血症方面的最新应用。此外,我们还讨论了聚合物介导疗法以及败血症的一些动态治疗方面。此外,文章还强调了利用药物递送治疗败血症所面临的挑战和局限性,并希望这篇综述能加快开发更有效的败血症疗法,促进从研究到实际临床应用的过渡。
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引用次数: 0
Mitochondrial targeted prodrug nanoparticles for chemo-photodynamic combinational tumour therapy 用于肿瘤化疗光动力联合疗法的线粒体靶向原药纳米颗粒
Q1 Engineering Pub Date : 2024-08-08 DOI: 10.1016/j.smaim.2024.08.002

Prodrug nanoparticles have been explored as an effective means for drug delivery because of controlled drug release in a stimulus-responsive manner. Organellar-targeted drug delivery could enhance the efficacy of cancer therapy. Herein, pH and light dual responsive mitochondrial targeted prodrug nanoparticles were designed to deliver both chemotherapeutic drugs and photosensitisers for enhanced antitumour efficacy. The prodrug nanoparticles (TPP-PEI-PheoA/ALG=DOX NPs, TPPAD NPs) are composed of a light-responsive mitochondrial targeted prodrug (triphenylphosphonium and pheophorbide A modified polyethyleneimine, TPP-PEI-PheoA) and a pH-responsive prodrug (doxorubicin conjugated alginate with Schiff's base bond, ALG=DOX). TPPAD NPs were prepared through electrostatic interaction. TPPAD NPs could simultaneously deliver DOX and PheoA to the tumour site by passive targeting effect, release drugs in a designed mode and deliver drugs to the target organelles. Moreover, TPPAD NP-based PDT could induce immunogenic cell death of tumour cells, thereby activating the immune system. TPPAD NPs greatly enhanced antitumour efficacy by combinational therapy. Taken together, this prodrug nanoparticle platform has appeared to be a simple and smart nanomedicine for targeted tumour combinational treatment.

原药纳米颗粒能以刺激响应的方式控制药物释放,因此被视为一种有效的给药手段。细胞器靶向给药可以提高癌症治疗的疗效。在此,我们设计了具有 pH 和光双重响应的线粒体靶向原药纳米颗粒,用于递送化疗药物和光敏剂,以增强抗肿瘤疗效。这种原药纳米颗粒(TPP-PEI-PheoA/ALG=DOX NPs,TPPAD NPs)由光响应线粒体靶向原药(三苯基膦和嗜磷酸盐 A 修饰的聚乙烯亚胺,TPP-PEI-PheoA)和 pH 响应原药(具有席夫碱键的多柔比星共轭藻酸盐,ALG=DOX)组成。TPPAD NPs 是通过静电作用制备的。TPPAD NPs可通过被动靶向效应将DOX和PheoA同时递送至肿瘤部位,以设计的模式释放药物并将药物递送至靶细胞器官。此外,基于 TPPAD NP 的光导疗法还能诱导肿瘤细胞的免疫性细胞死亡,从而激活免疫系统。TPPAD NP通过联合疗法大大提高了抗肿瘤疗效。综上所述,这种原药纳米粒子平台似乎是一种用于肿瘤靶向联合治疗的简单而智能的纳米药物。
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引用次数: 0
Pulmonary delivery of bioadhesive nanoparticles for ALI improvement and ARDS prevention with a single-dose administration 生物黏附性纳米颗粒的肺部给药,单剂量给药改善 ALI 和预防 ARDS
Q1 Engineering Pub Date : 2024-08-06 DOI: 10.1016/j.smaim.2024.08.001

Acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), is the major cause of intensive care unit death worldwide. ALI/ARDS is a common condition characterized by a storm of potent inflammatory cytokines. Lung delivery of glucocorticoids (GCs) by inhalation is a potential approach for ALI treatment and ARDS prevention; however, its efficacy is limited by the rapid clearance of GCs in lungs. In this study, we developed surface-modified poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with bioadhesive properties for local delivery to the epidermis of lung tissues, which exhibited prolonged release profile of payloads following intratracheal spraying administration. Compared with that of non-adhesive nanoparticles (NNPs), BNPs showed significantly enhanced adhesion and prolonged retention within lung tissues in vivo. Lipopolysaccharide (LPS)-induced ALI mice treated with betamethasone dipropionate (BD)-loaded BNPs showed significantly fewer lung histological alterations and less lung inflammation than those administered free BD or BD-loaded NNPs, indicating the enhanced therapeutic efficacy of BD/BNPs in ALI. In contrast, the features of ARDS were observed in the animal models without any treatments. Our findings demonstrated that pulmonary delivery of BNPs can maintain their same surface structures and continuously form covalent connections with the contacted tissues, emphasizing their potential to improve the therapeutic efficacy in ALI and prevent from ARDS.

急性呼吸窘迫综合征(ARDS)是急性肺损伤(ALI)的一种严重形式,是全球重症监护病房死亡的主要原因。ALI/ARDS是一种常见病,其特征是强效炎症细胞因子风暴。通过吸入肺部输送糖皮质激素(GCs)是治疗 ALI 和预防 ARDS 的一种潜在方法;然而,GCs 在肺部的快速清除限制了其疗效。在这项研究中,我们开发了具有生物粘附性的表面修饰聚(乳酸)-超支化聚甘油纳米颗粒(BNPs),用于局部输送到肺组织的表皮层。与非粘附性纳米颗粒(NNPs)相比,BNPs 在体内肺组织内的粘附性明显增强,保留时间更长。用二丙酸倍他米松(BD)负载的 BNPs 治疗脂多糖(LPS)诱导的 ALI 小鼠,其肺部组织学改变和肺部炎症明显少于用游离 BD 或 BD 负载的 NNPs 治疗的小鼠,这表明 BD/BNPs 对 ALI 的疗效更佳。相比之下,在未接受任何治疗的动物模型中观察到了 ARDS 的特征。我们的研究结果表明,肺输送 BNPs 可保持其相同的表面结构,并持续与接触的组织形成共价连接,这凸显了 BNPs 改善 ALI 疗效和预防 ARDS 的潜力。
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引用次数: 0
Advances in smart biomaterials that modulate the bone microenvironment to promote bone defect repair in diabetes mellitus 调节骨微环境以促进糖尿病患者骨缺损修复的智能生物材料的研究进展
Q1 Engineering Pub Date : 2024-07-31 DOI: 10.1016/j.smaim.2024.07.002

Diabetes mellitus (DM) is a chronic metabolic disorder that can affect the balance of bone metabolism and bone microenvironment, leading to impaired fracture healing. There are several underlying mechanisms which contributing to the impaired diabetic bone microenvironment such as hyperglycemia, the production of advanced glycation end products (AGEs), inflammation, and oxidative stress, etc. Recent studies have achieved great progress in developing novel smart biomaterials in improving the diabetic bone microenvironment to promote diabetic fracture healing. In this paper, we reviewed the mechanisms on DM-induced impaired fracture healing. Meanwhile, we also summarized the smart biomaterials used to improve the local microenvironment of diabetic fractures healing, which provides a novel perspective for the future treatment of fractures in diabetic patients.

糖尿病(DM)是一种慢性代谢性疾病,可影响骨代谢和骨微环境的平衡,导致骨折愈合受损。导致糖尿病骨微环境受损的潜在机制有多种,如高血糖、高级糖化终产物(AGEs)的产生、炎症和氧化应激等。最近的研究在开发新型智能生物材料改善糖尿病骨微环境以促进糖尿病骨折愈合方面取得了重大进展。本文综述了 DM 诱导骨折愈合受损的机制。同时,我们还总结了用于改善糖尿病骨折愈合局部微环境的智能生物材料,为未来糖尿病患者骨折的治疗提供了新的视角。
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引用次数: 0
Organic-inorganic nHA-Gelatin/Alginate high strength macroporous cryogel promotes bone regeneration 有机-无机 nHA-明胶/海藻酸高强度大孔低温凝胶促进骨再生
Q1 Engineering Pub Date : 2024-07-16 DOI: 10.1016/j.smaim.2024.07.001

Macroporous cryogel has the advantages of nutrient exchange and cell growth, and is an ideal material for tissue regeneration. In order to strengthen the machenical properties of cryogel for the widely use, a high strength gelatin/sodium alginate/nano hydroxyapatite (nHA) porous cryogel (GA-HA cryogel) was prepared by a simple freeze-thaw process. The mechanical strength of GA-HA cryogel increased significantly with the increase of nHA content. In vitro studies showed that GA-HA cryogel had good biocompatibility and no obvious cytotoxicity to MC3T3-E1 cells. The results of alkaline phosphatase activity assay and osteocalcin immunofluorescence staining showed that GA-HA1 porous hydrogel system could significantly increase the expression of MC3T3-E1 alkaline phosphatase and osteocalcin when the content of nHA was 1 ​%. In addition, porous GA-HA cryogel showed good performance in promoting bone regeneration in rat skull defect model. Therefore, the high-strength double network cryogel prepared in this study can provide new applications in bone repair and tissue regeneration.

大孔低温凝胶具有营养交换和细胞生长的优点,是组织再生的理想材料。为了增强低温凝胶的宏观性能,使其得到广泛应用,研究人员采用简单的冻融工艺制备了一种高强度明胶/海藻酸钠/纳米羟基磷灰石(nHA)多孔低温凝胶(GA-HA cryogel)。随着 nHA 含量的增加,GA-HA 低温凝胶的机械强度显著提高。体外研究表明,GA-HA 低温凝胶具有良好的生物相容性,对 MC3T3-E1 细胞无明显的细胞毒性。碱性磷酸酶活性测定和骨钙素免疫荧光染色结果表明,当nHA含量为1%时,GA-HA1多孔水凝胶系统能显著提高MC3T3-E1碱性磷酸酶和骨钙素的表达。此外,多孔 GA-HA 低温凝胶在促进大鼠颅骨缺损模型的骨再生方面表现良好。因此,本研究制备的高强度双网络低温凝胶可在骨修复和组织再生方面提供新的应用。
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引用次数: 0
Construction of an uricase/catalase/curcumin-co-loaded drug delivery system and its effect on hyper-uric acid-induced kidney injury 尿酸盐/催化剂/姜黄素载药系统的构建及其对高尿酸诱导的肾损伤的影响
Q1 Engineering Pub Date : 2024-06-06 DOI: 10.1016/j.smaim.2024.05.002
Yang Zhang , Xiaobo Li , Chunling Liang , Jianjia Feng , Chuyi Yu , Weichi Jiang , Keneng Cai , Wanying Chen , Wenli Cai , Feng Zeng , Qin Xu , Peng Chen , Jianming Liang

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

高尿酸(UA)诱导的肾损伤(HAKI)是由血液中过量的尿酸沉积到肾脏引起的。我们通过鞣酸与氯化铁的交联复合物反应,将尿酸酶(URI)、过氧化氢酶(CAT)和姜黄素(Cur)分子限制在单一结构(UC/Cur)中,同时保留其酶活性,用于治疗 HAKI。同时,通过三(2-羧乙基)膦(TCEP)将牛血清白蛋白(BSA)的二硫键与酶复合物交联形成巯基,成功制备了牛血清白蛋白-UC/Cur纳米颗粒。BSA-UC/Cur通过消除UA晶体和细胞内活性氧,明显减轻了MSU诱导的NLRP3炎性体通路激活和NRK-52e细胞的凋亡。更重要的是,BSA-UC/Cur 能稳定 HAKI 模型大鼠血液中 UA 的浓度,降低近端肾小管蛋白水平、线粒体肿胀和纤维化面积,减少基质金属蛋白酶(MMP)2、MMP9 和 NLRP3 的表达,同时增加紧密连接蛋白 ZO1 和 occludin 以及 TIMP-1 的表达。此外,BSA-UC/Cur 纳米粒子还降低了 CD8+ T 细胞和 M1 巨噬细胞的亚群比率,增加了 M2 巨噬细胞和 Treg 细胞的亚群比率。初步体内试验表明,长期静脉注射 BSA-UC/Cur 是安全的。因此,BSA-UC/Cur 可能是一种潜在的 HAKI 纳米治疗剂。
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引用次数: 0
Smart materials in medicine 5th anniversary 智能材料在医学中的应用 5 周年
Q1 Engineering Pub Date : 2024-05-14 DOI: 10.1016/j.smaim.2024.05.001
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引用次数: 0
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