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A hypoxia-targeting and hypoxia-responsive nano-probe for tumor detection and early diagnosis†
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-14 DOI: 10.1039/D4BM01499E
Yong Chen, Huimin Wang, Xiaodan Xu, Hongxia Xu, Bing Xiao, Pengcheng Yuan, Shiqun Shao, Wenjing Sun, Zhuxian Zhou, Youqing Shen and Jianbin Tang

Accurate imaging of tumor hypoxia in vivo is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine N-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.

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引用次数: 0
3D printing of wearable sensors with strong stretchability for myoelectric rehabilitation† 3D打印可穿戴式强拉伸肌电康复传感器。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-13 DOI: 10.1039/D4BM01434K
Jianan Zhan, Yueying Kong, Xi Zhou, Haihuan Gong, Qiwei Chen, Xianlin Zhang, Jiankai Zhang, Yilin Wang and Wenhua Huang

Myoelectric biofeedback (EMG-BF) is a widely recognized and effective method for treating movement disorders caused by impaired nerve function. However, existing EMG-feedback devices are almost entirely located in large medical centers, which greatly limits patient accessibility. To address this critical limitation, there is an urgent need to develop a portable, cost-effective, and real-time monitoring device that can transcend the existing barriers to the treatment of EMG-BF. Our proposed solution leverages polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) as core materials, ingeniously incorporating wood pulp nano celluloses (CNF-P)-Na+ to enhance the structural integrity. Additionally, the inclusion of nano-silica particles further augments the sensor's capabilities, enabling the creation of a stress-sensitive mineral ionization hydrogel sensor. This innovative approach not only capitalizes on the superior rheological properties of the materials but also, through advanced 3D printing technology, facilitates the production of a micro-scale structural hydrogel sensor with unparalleled sensitivity, stability, and durability. The potential of this sensor in the realm of human motion detection is nothing short of extraordinary. This development can potentially improve the treatment landscape for EMG-BF offering patients more convenient and efficient therapeutic options.

肌电生物反馈(EMG-BF)是一种被广泛认可的治疗神经功能受损引起的运动障碍的有效方法。然而,现有的肌电反馈设备几乎全部位于大型医疗中心,这极大地限制了患者的可及性。为了解决这一关键限制,迫切需要开发一种便携、经济、实时的监测设备,以超越肌电- bf治疗的现有障碍。我们提出的解决方案利用聚乙烯醇(PVA)和聚乙烯吡咯烷酮(PVP)作为核心材料,巧妙地结合木浆纳米纤维素(CNF-P)-Na+来增强结构完整性。此外,纳米二氧化硅颗粒的加入进一步增强了传感器的功能,使其成为一种应力敏感的矿物电离水凝胶传感器。这种创新的方法不仅利用了材料优越的流变特性,而且通过先进的3D打印技术,促进了具有无与伦比的灵敏度、稳定性和耐用性的微尺度结构水凝胶传感器的生产。这种传感器在人体运动检测领域的潜力是非凡的。这一发展可能会改善肌电- bf的治疗前景,为患者提供更方便、更有效的治疗选择。
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引用次数: 0
Ultrafine fiber-mediated transvascular interventional photothermal therapy using indocyanine green for precision embolization treatment† 超细纤维介导的经血管介入光热治疗吲哚菁绿精准栓塞治疗。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-13 DOI: 10.1039/D4BM01592D
Yingao Ma, Jingyu Xiao, Gina Jinna Chen, Hong Dang, Yaran Zhang, Xiaoqin He, Perry Ping Shum and Qiongyu Guo

Photothermal treatment has attracted immense interest as a promising approach for biomedical applications such as cancer ablation, yet its effectiveness is often limited by insufficient laser penetration and challenges in achieving efficient targeting of photothermal agents. Here we developed a transvascular interventional photothermal therapy (Ti-PTT), which employed a small-sized microcatheter (outer diameter: 0.60 mm, 1.8 Fr) equipped with an ultrafine optical fiber (diameter: 100 μm) capable of simultaneously delivering photothermal agents while performing 808 nm laser irradiation via an endovascular route. Specifically, we employed two types of indocyanine green (ICG)-based photothermal agents, i.e. ICG solution serving as a purely photothermal agent and ICG-ethiodized oil (ICG–EO) emulsion acting as a radiopaque photothermal embolic agent. Using the customized microcatheter with the ICG solution, both proximal and distal embolization were able to be performed in a rat liver model. Compared to the ICG solution, the ICG–EO emulsion dramatically enhanced the ICG retention time, enabling a photothermally triggered precision vascular blockade to induce local embolization of large tissue volumes in a rat kidney model with an unfavorable ICG leakage rate. The Ti-PTT paves the way to broadening the potential applications of photothermal therapy through combination with clinical intervention-based approaches.

光热治疗作为一种有前途的生物医学应用方法,如癌症消融,引起了人们的极大兴趣,但其有效性往往受到激光穿透不足和实现光热剂有效靶向的挑战的限制。在这里,我们开发了一种经血管介入光热疗法(Ti-PTT),它采用了一个小尺寸的微导管(外径:0.60 mm, 1.8 Fr),配备了超细光纤(直径:100 μm),能够在通过血管内途径进行808 nm激光照射的同时输送光热剂。具体来说,我们采用了两种基于吲哚菁绿(ICG)的光热剂,即ICG溶液作为纯粹的光热剂,ICG-乙硫化油(ICG- eo)乳剂作为不透射线的光热栓塞剂。使用定制的微导管与ICG溶液,可以在大鼠肝脏模型中进行近端和远端栓塞。与ICG溶液相比,ICG- eo乳状液显著提高了ICG保留时间,使光热触发的精确血管阻断能够在具有不利ICG泄漏率的大鼠肾脏模型中诱导大组织体积的局部栓塞。Ti-PTT通过结合临床干预方法,为扩大光热疗法的潜在应用铺平了道路。
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引用次数: 0
Biomaterial-based strategies for primary human corneal endothelial cells for therapeutic applications: from cell expansion to transplantable carrier 基于生物材料的原代人角膜内皮细胞治疗应用策略:从细胞扩增到可移植载体。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-13 DOI: 10.1039/D4BM00941J
Myagmartsend Enkhbat, Jodhbir S. Mehta, Gary S. L. Peh and Evelyn K. F. Yim

The treatment of corneal blindness due to corneal diseases and injuries often requires the transplantation of healthy cadaveric corneal endothelial graft tissue to restore corneal clarity and visual function. However, the limited availability of donor corneas poses a significant challenge in meeting the demand for corneal transplantation. As a result, there is a growing interest in developing strategies alleviate this unmet need, and one of the postulated approaches is to isolate and expand primary human corneal endothelial cells (HCECs) in vitro for use in cell therapy. This review summarizes the recent advancements in the expansion of HCECs using biomaterials. Two principal biomaterial-based approaches, including extracellular matrix (ECM) coating and functionalized synthetic polymers, have been investigated to create an optimal microenvironment for the expansion and maintenance of corneal endothelial cells (CECs). This review highlights the challenges and opportunities in expanding primary HCECs using biomaterials. It emphasizes the importance of optimizing biomaterial properties, cell culture conditions, and the roles of biophysical cues to achieve efficient expansion and functional maintenance of CECs. Biomaterial-based strategies hold significant promise for expanding primary HCECs and improving the outcomes of CEC transplantation. The integration of biomaterials as cell culture substrates and transplantable carriers offers a comprehensive approach to address the limitations associated with current corneal tissue engineering techniques.

由于角膜疾病和损伤导致的角膜失明的治疗往往需要移植健康的尸体角膜内皮移植组织来恢复角膜清晰度和视觉功能。然而,供体角膜的有限性对满足角膜移植的需求提出了重大挑战。因此,人们对开发缓解这一未满足需求的策略越来越感兴趣,其中一种假设的方法是在体外分离和扩增原代人角膜内皮细胞(HCECs)以用于细胞治疗。本文综述了利用生物材料扩大HCECs的最新进展。两种主要的基于生物材料的方法,包括细胞外基质(ECM)涂层和功能化合成聚合物,已经被研究为角膜内皮细胞(CECs)的扩张和维持创造了一个最佳的微环境。这篇综述强调了利用生物材料扩大原发性HCECs的挑战和机遇。它强调了优化生物材料特性、细胞培养条件和生物物理线索的重要性,以实现CECs的有效扩展和功能维持。基于生物材料的策略对于扩大原发性肝细胞癌和改善肝细胞癌移植的结果具有重要的前景。生物材料作为细胞培养基质和可移植载体的整合为解决当前角膜组织工程技术的局限性提供了一种全面的方法。
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引用次数: 0
Sulfonium-based polymethacrylamides for antimicrobial use: influence of the structure and composition† 抗菌用磺胺基聚丙烯酰胺:结构和组成的影响。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-13 DOI: 10.1039/D4BM01247J
Sidra Kanwal, Umer Bin Abdul Aziz, Elisa Quaas, Katharina Achazi and Daniel Klinger

We are facing a shortage of new antibiotics to fight against increasingly resistant bacteria. As an alternative to conventional small molecule antibiotics, antimicrobial polymers (AMPs) have great potential. These polymers contain cationic and hydrophobic groups and disrupt bacterial cell membranes through a combination of electrostatic and hydrophobic interactions. While most examples focus on ammonium-based cations, sulfonium groups are recently emerging to broaden the scope of polymeric therapeutics. Here, main-chain sulfonium polymers exhibit good antimicrobial activity. In contrast, the potential of side-chain sulfonium polymers remains less explored with structure–activity relationships still being limited. To address this limitation, we thoroughly investigated key factors influencing antimicrobial activity in side-chain sulfonium-based AMPs. For this, we combined sulfonium cations with different hydrophobic (aliphatic/aromatic) and hydrophilic polyethylene glycol (PEG) groups to create a library of polymers with comparable chain lengths. For all compositions, we additionally examined the position of cationic and hydrophobic groups on the polymer backbone, i.e., we systematically compared same center and different center structures. Bactericidal tests against Gram-positive and Gram-negative bacteria suggest that same center polymers are more active than different center polymers of similar clog P. Ultimately, sulfonium-based AMPs show superior bactericidal activity and selectivity when compared to their quaternary ammonium cationic analogues.

我们正面临着新抗生素短缺的问题,无法对抗越来越耐药的细菌。抗菌聚合物作为传统小分子抗生素的替代品,具有很大的发展潜力。这些聚合物含有阳离子和疏水基团,并通过静电和疏水相互作用的组合破坏细菌细胞膜。虽然大多数例子都集中在氨基阳离子上,但最近出现的磺酸基团扩大了聚合物治疗的范围。在这里,主链磺胺聚合物表现出良好的抗菌活性。相比之下,侧链磺酸聚合物的潜力仍然较少探索,结构-活性关系仍然有限。为了解决这一限制,我们深入研究了影响侧链磺胺基抗菌肽抗菌活性的关键因素。为此,我们将磺胺离子与不同的疏水(脂肪族/芳香族)和亲水聚乙二醇(PEG)基团结合起来,创建了一个具有相似链长的聚合物库。对于所有组成,我们还检查了阳离子和疏水性基团在聚合物主链上的位置,即,我们系统地比较了相同中心和不同中心结构。对革兰氏阳性菌和革兰氏阴性菌的杀菌试验表明,相同中心聚合物比相似clog P的不同中心聚合物更有活性。最终,与季铵盐阳离子类似物相比,磺胺基amp表现出优越的杀菌活性和选择性。
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引用次数: 0
Integrating microfluidics, hydrogels, and 3D bioprinting for personalized vessel-on-a-chip platforms 集成微流体,水凝胶和3D生物打印的个性化血管芯片平台。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-09 DOI: 10.1039/D4BM01354A
San Seint Seint Aye, Zhongqi Fang, Mike C. L. Wu, Khoon S. Lim and Lining Arnold Ju

Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of in vitro thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs. We discuss how these emerging technologies, particularly vessel-on-a-chip platforms, are enabling researchers to control previously unmanageable factors, thereby offering unprecedented opportunities to pinpoint specific clotting mechanisms. While PDMS-based devices offer optical transparency and fabrication ease, their inherent limitations, including non-physiological rigidity and surface properties, have driven the development of hydrogel-based systems that better mimic the extracellular matrix of blood vessels. The integration of microfluidics with biomimetic materials and tissue engineering approaches has led to the development of sophisticated models capable of simulating patient-specific vascular geometries, flow dynamics, and cellular interactions under highly controlled conditions. The advent of 3D bioprinting further enables the creation of complex, multi-layered vascular structures with precise spatial control over geometry and cellular composition. Despite significant progress, challenges remain in achieving long-term stability, incorporating immune components, and translating these models to clinical applications. By providing a comprehensive overview of current advancements and future prospects, this review aims to stimulate further innovation in thrombosis research and accelerate the development of more effective, personalized approaches to thrombosis prevention and treatment.

血栓形成是世界范围内发病率和死亡率的主要原因,由于生物体内凝血机制的复杂性,它对心血管医学提出了复杂的挑战。由于无法控制这些复杂系统中的变量,包括临床研究和动物模型在内的传统研究方法往往产生相互矛盾的结果,这突出了对更精确的调查工具的需求。这篇综述探讨了体外血栓模型的发展,从传统的聚二甲基硅氧烷(PDMS)为基础的微流体装置到先进的基于水凝胶的系统和尖端的生物3D打印血管结构。我们讨论了这些新兴技术,特别是血管芯片平台,如何使研究人员能够控制以前无法管理的因素,从而提供前所未有的机会来确定特定的凝血机制。虽然基于pdms的设备具有光学透明度和制造便利性,但其固有的局限性,包括非生理刚性和表面特性,推动了基于水凝胶的系统的发展,更好地模拟血管的细胞外基质。微流体与仿生材料和组织工程方法的整合导致了复杂模型的发展,这些模型能够在高度控制的条件下模拟患者特定的血管几何形状、流动动力学和细胞相互作用。3D生物打印的出现进一步使复杂的多层血管结构的创建具有精确的空间控制几何形状和细胞组成。尽管取得了重大进展,但在实现长期稳定性、纳入免疫成分以及将这些模型转化为临床应用方面仍然存在挑战。通过对目前的研究进展和未来展望的全面概述,本文旨在促进血栓研究的进一步创新,加快血栓预防和治疗的更有效、个性化方法的发展。
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引用次数: 0
The role of human intestinal mucus in the prevention of microplastic uptake and cell damage† 人体肠道粘液在预防微塑料摄取和细胞损伤中的作用。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-08 DOI: 10.1039/D4BM01574F
Ellen W. van Wijngaarden, Sandra L. Arias, Matthew Rhee, Meredith N. Silberstein and Ilana L. Brito

An increase in plastic waste and its release into the environment has led to health concerns over microplastics (MPs) in the environment. The intestinal mucosal layer is a key defense mechanism against ingested MPs, preventing the migration of particles to other parts of the body. MP migration through intestinal mucus is challenging to study due to difficulties in obtaining intact mucus layers for testing and numerous formulations, shapes, and sizes of microplastics. Previous studies have primarily used mucus from animals, hydrogel models, and mucus samples from other parts of the body as substitutes. This study examines how different MP compositions, sizes (40–500 nm), and surface functionalizations alter MP migration through human intestinal mucus; how the mucus layer protects cells from MP uptake, toxicity, and inflammation; and how the intestinal mucus prevents the migration of other environmental toxins via MP particles. The presence of a mucus layer also provides critical protection against cytotoxicity, reactive oxygen species production, and uptake for all particles tested, although certain functionalizations, such as streptavidin, are particularly harmful to cells with high toxicity and inflammation. Understanding the properties that assist of impede the diffusion of MPs through mucus is relevant to the overall bioaccumulation and health effects of MPs as well as drug delivery purposes.

塑料垃圾的增加及其向环境中的释放引发了对环境中微塑料(MPs)的健康担忧。肠粘膜层是抵御摄入的MPs的关键防御机制,防止颗粒迁移到身体的其他部位。由于难以获得完整的黏液层进行测试,以及微塑料的配方、形状和大小不一,因此研究微塑料通过肠道粘液的迁移具有挑战性。以前的研究主要使用动物黏液、水凝胶模型和身体其他部位的黏液样本作为替代品。本研究探讨了不同的MP组成、尺寸(40-500 nm)和表面功能化如何改变MP通过人肠道粘液的迁移;黏液层如何保护细胞免受MP摄取、毒性和炎症的影响;以及肠道粘液如何阻止其他环境毒素通过MP颗粒迁移。黏液层的存在也为所有被测试的颗粒提供了抗细胞毒性、活性氧产生和摄取的关键保护,尽管某些功能化物,如链霉亲和素,对具有高毒性和炎症的细胞特别有害。了解帮助或阻碍MPs通过黏液扩散的特性与MPs的整体生物积累和健康影响以及药物递送目的有关。
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引用次数: 0
Biofabricated tissue model for determining biocompatibility of metallic coatings† 测定金属涂层生物相容性的生物制造组织模型。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-08 DOI: 10.1039/D4BM01335B
Taha Cagri Senocak, Pavan Kumar Reddy Gudeti, Joanna Żur-Pińska and Małgorzata Katarzyna Włodarczyk-Biegun

Metallic biomaterials are extensively used in orthopedics and dentistry, either as implants or coatings. In both cases, metal ions come into contact with surrounding tissues causing a particular cell response. Here, we present a biofabricated in vitro tissue model, consisting of a hydrogel reinforced with a melt electrowritten mesh, to study the effects of bound and released metal ions on surrounding cells embedded in a hydrogel matrix. We evaluate the biocompatibility, bioactivity, and antibacterial properties of these metal coatings. Our approach involves integrating physical vapour deposition coating technology with 3D bioprinting methods. To produce tissue models, melt electrowritten (MEW) meshes composed of polycaprolactone (PCL) were printed and integrated into cell-laden methacrylated galatin (GelMa). The mouse embryonic fibroblast cell line (NIH3T3) was used. GelMa concentration and printing parameters for MEW were adjusted and mechanical analysis of the models was performed to find the optimal material composition. Optimized models were placed on the glass slide surfaces coated with typically non-toxic metals, i.e. titanium (Ti), tantalum (Ta), zirconium (Zr), silver (Ag), tungsten (W), and niobium (Nb). Except for W, all other coatings were stable in a physiological wet environment, as studied by SEM. The viability of the cells at different distances from the coated surface was analyzed. Antibacterial tests against pathogens Staphylococcus aureus and Escherichia coli were used to assess the models’ resistance, important for infection control. While Ag coatings showed toxicity, Nb, Ta, Ti, and Zr coatings promoted fibroblast growth, with the highest cell viability after 14 days of culture revealed for Ta and Nb. The strongest antimicrobial effect against E. coli and S. aureus was observed for Ag and W, while Ta exhibited antibacterial activity only against S. aureus. From a broader perspective, our work offers an effective 3D in vitro model for an in-depth characterization of the biocompatibility of metals and metal coatings.

金属生物材料广泛应用于骨科和牙科,无论是作为植入物还是涂层。在这两种情况下,金属离子都与周围组织接触,引起特定的细胞反应。在这里,我们提出了一个生物制造的体外组织模型,由一个由熔融电写网增强的水凝胶组成,以研究结合和释放的金属离子对嵌入在水凝胶基质中的周围细胞的影响。我们评估了这些金属涂层的生物相容性、生物活性和抗菌性能。我们的方法包括将物理气相沉积涂层技术与3D生物打印方法相结合。为了制造组织模型,打印由聚己内酯(PCL)组成的熔融电写入(MEW)网,并将其整合到细胞负载的甲基丙烯酸半乳糖(GelMa)中。采用小鼠胚胎成纤维细胞系NIH3T3。通过调整凝胶浓度和MEW打印参数,对模型进行力学分析,找到最佳的材料组成。优化后的模型被放置在涂有典型无毒金属的玻片表面,即钛(Ti)、钽(Ta)、锆(Zr)、银(Ag)、钨(W)和铌(Nb)。扫描电镜显示,除W外,其他涂层在生理湿环境下均保持稳定。分析了细胞在离涂层表面不同距离处的活力。通过对病原菌金黄色葡萄球菌和大肠杆菌的抗菌试验来评估模型的耐药性,这对感染控制具有重要意义。Ag包被表现出毒性,而Nb、Ta、Ti和Zr包被促进成纤维细胞生长,培养14天后,Ta和Nb的细胞活力最高。Ag和W对大肠杆菌和金黄色葡萄球菌的抑菌作用最强,而Ta仅对金黄色葡萄球菌有抑菌作用。从更广泛的角度来看,我们的工作为深入表征金属和金属涂层的生物相容性提供了有效的3D体外模型。
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引用次数: 0
Integrating 3D printing of biomaterials with nitric oxide release† 将生物材料3D打印与一氧化氮释放相结合。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-07 DOI: 10.1039/D4BM01304B
Herllan V. de Almeida, Mateus P. Bomediano, Daniele M. Catori, Elizaura H. C. Silva and Marcelo G. de Oliveira

The pivotal roles played by nitric oxide (NO) in tissue repair, inflammation, and immune response have spurred the development of a wide range of NO-releasing biomaterials. More recently, 3D printing techniques have significantly broadened the potential applications of polymeric biomaterials in biomedicine. In this context, the development of NO-releasing biomaterials that can be fabricated through 3D printing techniques has emerged as a promising strategy for harnessing the benefits of localized NO release from implantable devices, tissue regeneration scaffolds, or bandages for topical applications. Although 3D printing techniques allow for the creation of polymeric constructs with versatile designs and high geometric precision, integrating NO-releasing functional groups or molecules into these constructs poses several challenges. NO donors, such as S-nitrosothiols (RSNOs) or diazeniumdiolates (NONOates), may release NO thermally, complicating their incorporation into resins that require heating for extrusion-based 3D printing. Conversely, NO released photochemically from RSNOs effectively inhibits radical propagation, thus hindering photoinduced 3D printing processes. This review outlines the primary strategies employed to overcome these challenges in developing NO-releasing biomaterials via 3D printing, and explores future prospects in this rapidly evolving field.

一氧化氮(NO)在组织修复、炎症和免疫反应中发挥的关键作用刺激了各种NO释放生物材料的发展。最近,3D打印技术大大拓宽了高分子生物材料在生物医学中的潜在应用。在这种情况下,可以通过3D打印技术制造的NO释放生物材料的开发已经成为一种有前途的策略,用于利用可植入装置,组织再生支架或局部应用绷带的局部NO释放的好处。尽管3D打印技术允许创建具有多用途设计和高几何精度的聚合物结构,但将no释放官能团或分子集成到这些结构中提出了几个挑战。NO供体,如s -亚硝基硫醇(RSNOs)或二氮双酸酯(NONOates),可能会通过热释放NO,使其与需要加热的树脂结合变得复杂。相反,从RSNOs光化学释放的NO有效地抑制了自由基的传播,从而阻碍了光诱导3D打印过程。本文概述了通过3D打印开发no释放生物材料克服这些挑战的主要策略,并探讨了这一快速发展领域的未来前景。
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引用次数: 0
Ganglioside-incorporating lipid nanoparticles as a polyethylene glycol-free mRNA delivery platform† 结合神经节苷脂纳米颗粒作为无聚乙二醇mRNA传递平台。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-07 DOI: 10.1039/D4BM01360C
Yafi S. Permana, Mincheol Jang, Kyunghwan Yeom, Erinn Fagan, Yong Jae Kim, Joon Hyeok Choi and Ji-Ho Park

Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative. Physicochemical characterization showed that ganglioside-LNPs exhibited superior stability throughout prolonged cold storage compared to stealth-free LNPs, preventing particle aggregation. Additionally, there was no significant change in particle size after serum incubation, indicating the ability of ganglioside to prevent unwanted serum protein adsorption. These results exemplify the effective stealth properties of ganglioside. Furthermore, ganglioside-LNPs exhibited significantly higher mRNA transfection in vivo after intravenous administration compared to stealth-free LNPs. The ability of ganglioside to confer excellent stealth properties to LNPs while still enabling in vivo mRNA expression makes it a promising candidate as a natural substitute for immunogenic PEG in mRNA-LNP delivery platforms, contributing to the future advancement of gene therapy.

聚乙二醇(PEG)被广泛应用于脂质纳米颗粒(LNP)配方中,以获得足够的稳定性。然而,研究发现,在PEGylated LNP治疗后,存在抗peg中和抗体,这与过敏反应、加速LNP清除和货物过早释放有关。在这里,我们报告了LNPs的发展,包括神经节苷脂,一种天然存在的隐形脂质,作为无peg的替代品。物理化学表征表明,与无隐形LNPs相比,神经节苷脂-LNPs在长时间冷藏过程中表现出优越的稳定性,可以防止颗粒聚集。此外,血清孵育后颗粒大小无明显变化,表明神经节苷脂能够防止不需要的血清蛋白吸附。这些结果证明了神经节苷脂的有效隐身特性。此外,与无隐形LNPs相比,神经节苷脂-LNPs在静脉注射后的体内mRNA转染量显著增加。神经节苷脂能够赋予LNPs良好的隐身特性,同时仍能在体内表达mRNA,这使其成为mRNA- lnp递送平台中免疫原性PEG的天然替代品,有助于未来基因治疗的发展。
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