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A trimodal magnetic navigation-enhanced nanoplatform for spatiotemporally controlled chemo-photodynamic synergistic cancer therapy 用于时空控制化学光动力协同癌症治疗的三模态磁导航增强纳米平台。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-03 DOI: 10.1039/D5BM00579E
Cui Ma, Yaqi Cui, Bailong Liu, Min Liu, Xia Chen and Biao Dong

Malignant tumors pose a serious threat to human health with their high incidence and mortality rates. Although chemotherapeutic agents such as doxorubicin (DOX) exhibit significant antitumor efficacy, their non-specific distribution leads to toxic side effects and mono-chemotherapy fails to achieve complete tumor eradication, significantly limiting clinical applications. This study presents the development and evaluation of a multifunctional nanoplatform, Fe3O4@Ce6-DOX@liposome, which integrates magnetic targeting, chemotherapy, and photodynamic therapy (PDT) for enhanced tumor treatment. The nanoparticles (NPs) were engineered to co-deliver the chemotherapeutic drug DOX and the photosensitizer chlorin e6 (Ce6), while superparamagnetic Fe3O4 enabled external magnetic guidance. In vitro studies in MCF-7 cells demonstrated the system's light-activated cytotoxicity, with confocal microscopy revealing precise spatiotemporal control over drug release and ROS generation. In vivo evaluation in 4T1 tumor-bearing mice showed that magnetic navigation significantly enhanced tumor accumulation of NPs, leading to 73% tumor growth inhibition through synergistic chemo-PDT effects. The combination of magnetic targeting and dual therapeutic modalities resulted in superior antitumor efficacy compared to individual treatments, with minimal systemic toxicity. These findings highlight the potential of this multifunctional nanoplatform as a precise and effective strategy for solid tumor therapy, offering improved targeting and reduced off-target effects compared to conventional treatments.

恶性肿瘤发病率高、死亡率高,严重威胁着人类健康。虽然多柔比星(DOX)等化疗药物具有显著的抗肿瘤疗效,但其非特异性分布导致毒副作用,单次化疗不能完全根除肿瘤,极大地限制了临床应用。本研究提出了一种多功能纳米平台Fe3O4@Ce6-DOX@脂质体的开发和评估,该脂质体集成了磁靶向、化疗和光动力治疗(PDT),以增强肿瘤治疗。纳米颗粒(NPs)被设计用于共同递送化疗药物DOX和光敏剂氯e6 (Ce6),而超顺磁性的Fe3O4则用于外部磁引导。MCF-7细胞的体外研究表明,该系统具有光激活的细胞毒性,共聚焦显微镜显示了对药物释放和ROS生成的精确时空控制。4T1荷瘤小鼠体内评价显示,磁导航可显著增强NPs在肿瘤中的蓄积,通过协同化疗- pdt效应抑制肿瘤生长73%。与单独治疗相比,磁性靶向和双重治疗方式的结合产生了更好的抗肿瘤效果,并且全身毒性最小。这些发现突出了这种多功能纳米平台作为一种精确有效的实体肿瘤治疗策略的潜力,与传统治疗相比,它提供了更好的靶向性和更少的脱靶效应。
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引用次数: 0
Native adenosine A2A receptor solubilisation by a library of amphipathic copolymers 两亲共聚物库对天然腺苷A2A受体的增溶作用。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-27 DOI: 10.1039/D5BM01011J
Michelle D. Farrelly, Nazanin Mohebali, Emma Dal Maso, Cameron J. Nowell, Denise Wootten, Patrick M. Sexton, Lisandra L. Martin and San H. Thang

Polymer nanodiscs are a research tool that allows membrane proteins (MPs) to be encapsulated by a surrounding amphipathic polymer, isolated and studied to understand their structural and physiological properties. An advantage of using polymer nanodiscs over other membrane mimetics can be found in their ability to natively solubilise membrane proteins (MPs) within an annulus of cellular phospholipids, however, potential polymer interactions with membrane constituents can hinder MP activity making the selection of a suitable polymer critical. This work demonstrates the native solubilisation of G-protein coupled A2A adenosine receptor (A2AR) by polymers with alternating units and cationic charge, poly(N-methyl-4-vinyl pyridinium iodide-co-N-alkyl-maleimides) (poly(MVP-co-AlkylMs)), and novel statistical copolymers with pseudozwitterionic charge, poly(potassium 3-sulfopropyl methacrylate-co-2-(trimethyl-amino) ethyl methacrylate-co-n-butyl methacrylate) (poly(KSPMA-co-TMAEMA-co-BMA)), both synthesised using RAFT polymerisation. After surveying a library of polymers within each class, A2AR extraction was the most efficient using poly(MVP-co-BM) (1 : 1 MVP : BM) and poly(KSPMA-co-TMAEMA-co-BMA) (1 : 1 : 1 KSPMA : TMAEMA : BMA). The optimal pH, temperature, solubilisation time, polymer concentration and ionic strength conditions required for extracting A2AR were identified and enabled a large-scale A2AR-nanodisc preparation. The yield of A2AR-poly(MVP-co-BM) was superior to A2AR-poly(KSPMA-co-TMAEMA-co-BMA) nanodiscs after affinity purification. Functional assessment of the reconstituted receptors was undertaken using fluorescence correlation spectroscopy (FCS) to determine the ligand binding capacity of A2AR stabilised within an alternating cationic poly(MVP-co-BM). These native nanodiscs retained their ability to specifically bind A2AR ligand antagonists.

聚合物纳米盘是一种研究工具,它允许膜蛋白(MPs)被周围的两亲性聚合物包裹,分离和研究它们的结构和生理特性。与其他膜模拟物相比,使用聚合物纳米盘的优势在于它们能够在细胞磷脂环内天然溶解膜蛋白(MPs),然而,潜在的聚合物与膜成分的相互作用会阻碍MP的活性,这使得选择合适的聚合物变得至关重要。这项工作证明了g蛋白偶联A2A腺苷受体(A2AR)的天然增溶作用是由具有交替单元和阳离子电荷的聚合物,聚(n-甲基-4-乙烯基碘化吡啶-co-n-烷基-马来酰亚胺)(聚(MVP-co-AlkylMs))和具有伪十二离子电荷的新型统计共聚物,聚(3-甲基丙烯酸磺丙基钾-co-2-(三甲基-氨基)甲基丙烯酸乙基-co-正丁基甲基丙烯酸酯)(聚(KSPMA-co-TMAEMA-co-BMA)),两者都是用RAFT聚合合成的。在调查了每个类别的聚合物库后,A2AR提取效率最高的是poly(MVP-co-BM) (1:1 MVP: BM)和poly(KSPMA-co-TMAEMA-co-BMA) (1:1: 1 KSPMA: TMAEMA: BMA)。确定了提取A2AR所需的最佳pH、温度、溶解时间、聚合物浓度和离子强度条件,实现了A2AR纳米片的大规模制备。亲和纯化后的A2AR-poly(MVP-co-BM)的产率优于A2AR-poly(kspma -co- tmama -co- bma)纳米片。利用荧光相关光谱(FCS)对重组受体进行功能评估,以确定在交替阳离子聚合物(MVP-co-BM)中稳定的A2AR的配体结合能力。这些天然纳米圆盘保留了特异性结合A2AR配体拮抗剂的能力。
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引用次数: 0
Rapid and label-free isolation of human peripheral blood monocytes using a reversible CD36-binding aptamer for cell capture 使用可逆的cd36结合适体进行细胞捕获的人外周血单核细胞的快速和无标记分离。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-27 DOI: 10.1039/D5BM01232E
Melissa Ling, Nataly Kacherovsky, Abe Y. Wu, Minjian Ni, Jessica A. Hamerman and Suzie H. Pun

Monocytes are mononuclear phagocytes crucial for tissue repair, pathogen clearance, and immune surveillance. Comprising 2–10% of all human blood peripheral leukocytes, monocytes are precursors to macrophages and dendritic cells and can be leveraged for diagnostics and treatment of various diseases, such as cancer and autoimmune conditions. Current methods of monocyte isolation for these applications, such as plastic adhesion, magnetic-activated antibody-based selection, and counterflow centrifugal elutriation are limited by either low purity and viability or costly equipment and reagents. Here, we develop and optimize an aptamer-based method for traceless isolation of monocytes from peripheral blood mononuclear cells at low cost with high purity and yield, and with minimal activation and immunogenic risks. We identify and use CD36 as a novel selection marker for monocyte isolation and confirm that monocytes isolated using our CD36-binding aptamer possess similar phenotypes to monocytes isolated from anti-CD14 and anti-CD36 antibodies with higher, unperturbed CD14 and CD36 expression.

单核细胞是单核吞噬细胞,对组织修复、病原体清除和免疫监视至关重要。单核细胞占所有人类血液外周白细胞的2-10%,是巨噬细胞和树突状细胞的前体,可用于诊断和治疗各种疾病,如癌症和自身免疫性疾病。目前用于这些应用的单核细胞分离方法,如塑料粘附,基于磁激活抗体的选择和逆流离心洗脱,受到低纯度和活力或昂贵的设备和试剂的限制。在这里,我们开发并优化了一种基于适配体的方法,以低成本、高纯度和产量、最小的激活和免疫原性风险从外周血单核细胞中无迹分离单核细胞。我们鉴定并使用CD36作为单核细胞分离的新选择标记,并证实使用我们的CD36结合适体分离的单核细胞具有与从抗CD14和抗CD36抗体分离的单核细胞相似的表型,具有更高的、不受干扰的CD14和CD36表达。
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引用次数: 0
Correction: Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels 修正:在细胞负载明胶甲基丙烯酰水凝胶中选择光引发剂的设计考虑。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-27 DOI: 10.1039/D5BM90068A
Elvan Dogan, Ann Austin, Ayda Pourmostafa, Swaprakash Yogeshwaran, Hossein Goodarzi Hosseinabadi and Amir K. Miri

Correction for ‘Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels’ by Elvan Dogan et al., Biomater. Sci., 2025, https://doi.org/10.1039/d5bm00550g.

修正了Elvan Dogan等人在Biomater发表的“载细胞明胶甲基丙烯酰水凝胶中光引发剂选择的设计考虑”。科学。, 2025, https://doi.org/10.1039/d5bm00550g。
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引用次数: 0
Recent developments and prospects of inorganic nanozymes for biomedical applications 无机纳米酶在生物医学领域的研究进展与展望。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-24 DOI: 10.1039/D5BM01151E
Siqi Zhan, Yan Fu, Hong Yu Yang and Doo Sung Lee

The development of inorganic nanozymes has revolutionized the field of nanotechnology by providing a new class of catalytic materials that exhibit enzyme-like activities. Compared with traditional natural enzymes, nanozymes have broad application prospects in the field of biomedicine due to their higher chemical stability, stronger environmental adaptability, and ability to maintain their activity under extreme conditions. To provide a comprehensive overview of the recent progress made in this field, herein, an overview of inorganic nanozymes for biomedical applications is provided. In this review, the structure, synthesis methods, and catalytic mechanism of inorganic nanozymes are summarized. Subsequently, the latest progress of various inorganic nanozymes for the applications in biomedicine is reviewed, including diagnostic applications, therapeutic applications and drug delivery systems. Then, the recent developments in the modification and multifunctionalization of novel inorganic nanozymes are discussed. Finally, the challenges and prospects of inorganic nanozymes in the field of biomedicine are highlighted and pointed out. We hope that this timely review can further advance this promising field.

无机纳米酶的发展为纳米技术领域带来了革命性的变化,它提供了一类具有酶样活性的新型催化材料。与传统的天然酶相比,纳米酶具有更高的化学稳定性、更强的环境适应性以及在极端条件下保持活性的能力,在生物医学领域有着广阔的应用前景。为了全面概述这一领域的最新进展,本文对无机纳米酶在生物医学领域的应用进行了综述。本文综述了无机纳米酶的结构、合成方法和催化机理。随后,综述了各种无机纳米酶在生物医学领域的最新应用进展,包括诊断应用、治疗应用和给药系统。然后,讨论了近年来新型无机纳米酶在改性和多功能化方面的研究进展。最后,对无机纳米酶在生物医学领域面临的挑战和前景进行了展望。我们希望这一及时的审查能够进一步推动这一有前途的领域。
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引用次数: 0
Catechol isomers for moisture initiated bioadhesives 水引发生物粘合剂用儿茶酚异构体。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-24 DOI: 10.1039/D5BM01338K
Konrad Kozlowski, Animesh Ghosh, Zong Yao Liu, Zhonghan Zhang, Shuzhou Li and Terry W. J. Steele

While catechol chemistry is widely known, the selection of catechols applied for resins and adhesive purposes has relied almost exclusively on L-dopamine variants. Herein five catechol isomers evaluate ortho, meta, and para dihydroxybenzene (DHB) structures on adhesion related mechanical properties, including organic/aqueous stability, gelation time, and adhesion strength on soft substrates. A model system evaluates the catechol–aldehyde isomers through Schiff base grafting to an amine rich macromolecule, branched polyethylenimine. This work evaluates how grafted-catechol isomers can be exploited to tune reactivity to both solvent and external stimuli. The formulations allow a range of sensitivity, from designs that observe gelation time within minutes of water exposure, to water-stable formulations that can be cured through via voltage stimulation.

虽然儿茶酚化学已广为人知,但用于树脂和粘合剂用途的儿茶酚的选择几乎完全依赖于l -多巴胺变体。在本研究中,五种儿茶酚异构体评价了邻位、间位和对二羟基苯(DHB)结构对黏附相关力学性能的影响,包括有机/水稳定性、凝胶化时间和在软基质上的黏附强度。通过希夫碱接枝富胺大分子支链聚乙烯亚胺,建立了儿茶酚醛异构体的模型体系。这项工作评估了接枝儿茶酚异构体如何被利用来调整对溶剂和外部刺激的反应性。该配方具有一系列的灵敏度,从在水暴露几分钟内观察凝胶时间的设计,到可以通过电压刺激固化的水稳定配方。
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引用次数: 0
Mussel-inspired hydrogels with wet adhesion and anti-inflammatory properties for oral and pressure ulcers 以贻贝为灵感的水凝胶,具有湿润粘连和抗炎特性,适用于口腔溃疡和压力性溃疡。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-22 DOI: 10.1039/D5BM01231G
Wenjie Zhang, Yuchen Gu, Xinxin Zou, Ziyi Huang, Juan Ding, Jinlong Liao, Jingrong Yu, Jie Zhao, Shuo Zhang and Fengjie Huang

The etiology of oral ulcers is complex, primarily comprising external physical and chemical stimuli, immune imbalances, and various diseases. Pressure ulcers are mainly caused by continuous or intermittent pressure that damages the skin and underlying tissues. The healing process for both types of ulcers is similar to wound healing, including stages such as inflammation, proliferation, and remodeling. However, some clinically used treatments have issues such as significant side effects, high costs, low adhesion, and insufficient mechanical strength, which can negatively affect the patient's physical and mental health. In this study, we designed a mussel-inspired hydrogel (GD3M4), which consists of dopamine-grafted gelatin (GelDA), aldehyde-modified hyaluronic acid (OHA), and methacrylate gelatin (GelMA). This hydrogel can sustain adhesion for 48 hours in artificial saliva. In compression tests, the GD3M4 hydrogel showed a compression modulus of nearly 1.26 MPa, demonstrating excellent compressive strength to adapt to complex in vivo and in vitro environments. The DCFH-DA experiments showed that the GD3M4 hydrogel has good antioxidant properties. In both the mouse oral ulcer model and pressure ulcer model, the GD3M4 hydrogel exhibited excellent ulcer-healing effects by modulating the expression of inflammatory factors and epidermal growth. In conclusion, the GD3M4 hydrogel provides a promising therapeutic strategy for promoting the healing of oral ulcers and pressure ulcers.

口腔溃疡的病因复杂,主要包括外部物理和化学刺激、免疫失衡和各种疾病。压疮主要是由于持续或间歇的压力损害皮肤和皮下组织而引起的。这两种溃疡的愈合过程与伤口愈合相似,包括炎症、增殖和重塑等阶段。然而,临床上使用的一些治疗方法存在副作用大、费用高、粘连度低、机械强度不足等问题,对患者的身心健康产生负面影响。在这项研究中,我们设计了一种以贻贝为灵感的水凝胶(GD3M4),它由多巴胺接枝明胶(GelDA)、醛修饰透明质酸(OHA)和甲基丙烯酸酯明胶(GelMA)组成。这种水凝胶可以在人工唾液中保持48小时的粘连。在压缩试验中,GD3M4水凝胶的压缩模量接近1.26 MPa,表现出优异的抗压强度,能够适应复杂的体内和体外环境。DCFH-DA实验表明,GD3M4水凝胶具有良好的抗氧化性能。在小鼠口腔溃疡模型和压疮模型中,GD3M4水凝胶通过调节炎症因子的表达和表皮生长表现出良好的溃疡愈合作用。总之,GD3M4水凝胶为促进口腔溃疡和压疮的愈合提供了一种有前景的治疗策略。
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引用次数: 0
Military regenerative medicine 军事再生医学。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-22 DOI: 10.1039/D5BM01098E
Ang Li, João F. Mano, Laurent David and Andy Tay

Amid the rising toll of war-associated deaths and injuries and escalating conflicts between countries, there is a strong need to manage complex battlefield injuries by preventing further deterioration and accelerating the repair of damaged tissues. Global military powers, including the USA and China, have established scientific facilities for dedicated research into military regenerative medicine. However, there remains a gap, as most reported medical devices created for tissue repair are unsuitable for use on battlefields. In this perspective, we argue why now is the golden time for countries to invest in military regenerative medicine, and we propose the use of RIPE (Restorative, Individualized, Portable and Emergency) criteria to optimize technologies for tackling battlefield injuries, including rapid hemostasis, immobilization, tissue repair, and functional reconstruction. Similar to technologies such as blood plasma transfusion and portable ultrasound, which were originally developed through military investment and later found highly valuable for civilian medical use, timely investment in military regenerative medicine, as we argue, will have a positive spillover impact on public healthcare programs in the future.

在与战争有关的伤亡人数不断上升以及国家间冲突不断升级的情况下,迫切需要通过防止进一步恶化和加速受损组织的修复来管理复杂的战场伤害。包括美国和中国在内的全球军事大国已经建立了专门研究军事再生医学的科学设施。然而,仍然存在差距,因为大多数报道的用于组织修复的医疗设备不适合在战场上使用。从这个角度来看,我们讨论了为什么现在是各国投资军事再生医学的黄金时机,我们建议使用RIPE(恢复性、个性化、便携式和紧急)标准来优化处理战场伤害的技术,包括快速止血、固定、组织修复和功能重建。类似于血浆输注和便携式超声等技术,这些技术最初是通过军事投资开发的,后来被发现在民用医疗方面具有很高的价值,我们认为,及时投资军事再生医学,将对未来的公共医疗保健计划产生积极的溢出影响。
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引用次数: 0
The evaluation of platelet lysate incorporation into the microfracture clot in a pig model. 猪模型中血小板裂解液掺入微骨折凝块的评价。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-21 DOI: 10.1039/d5bm00372e
Hanna Solomon, Julie Gordon, Maddie Hasson, Hannah Arnade, Jordan Parker, Beatriz Dias, Amogh Magesh, William X Patton, John F Peroni, Jay M Patel

Cartilage injuries present a significant clinical burden due to the tissue's limited regenerative capacity. Microfracture (Mfx) remains the gold standard of cartilage repair but often results in inadequate defect fill and inferior tissue formation. Point-of-care augmentations to the Mfx environment represent implementable and cost-effective methods to enhance outcomes. The objective of this study was to evaluate platelet lysate (PL) as an adjuvant to microfracture-based cartilage repair, with the goal of maintaining tissue volume and promoting functional repair. The impact of PL on the activity of marrow-derived cells (MDCs) was first evaluated in monolayer culture, which demonstrated an increase in cellular area and proliferation. Next, PL was incorporated into fibrin gels (to mimic fibrin-rich Mfx), and MDCs encapsulated within PL-containing fibrin gels exhibited increased proliferation, increased cellular area, and reduced fibrosis markers. PL incorporation into fibrin gels led to clear changes to initial nanostructure and an increase in initial mechanical properties, which resulted in less MDC-mediated contraction during culture. These findings suggested that time-zero augmentation of Mfx with PL may alter both cellular signaling and Mfx clot structure/remodeling. Finally, PL-augmented Mfx was evaluated in a pig trochlear osteochondral defect model (t = 5 weeks). While PL-treated defects exhibited reduced contraction and improved macroscopic appearance over Mfx alone, micro-CT and mechanical testing revealed no significant differences in subchondral bone remodeling or repair tissue stiffness. Histological analysis and grading showed no significant improvements in cartilage repair quality across treatment groups, suggesting that while PL may influence early clot stability, its effects on long-term tissue maturation remain uncertain. "Future studies are needed to determine whether PL-based augmentation provides sustained functional benefits, potentially in combination with additional biological or mechanical strategies".

由于组织的再生能力有限,软骨损伤是一个重要的临床负担。微骨折(Mfx)仍然是软骨修复的金标准,但往往导致缺损填充不足和组织形成不良。医疗点对Mfx环境的增强是一种可实施且具有成本效益的方法,可以提高结果。本研究的目的是评估血小板裂解液(PL)作为微骨折软骨修复的辅助剂,目的是维持组织体积和促进功能修复。PL对骨髓源性细胞(MDCs)活性的影响首先在单层培养中进行了评估,结果显示细胞面积和增殖增加。接下来,将PL掺入纤维蛋白凝胶中(模拟富含纤维蛋白的Mfx),包裹在含有PL的纤维蛋白凝胶中的MDCs表现出增殖增加、细胞面积增加和纤维化标志物减少。PL掺入纤维蛋白凝胶导致初始纳米结构的明显变化和初始力学性能的增加,从而导致培养过程中mdc介导的收缩减少。这些发现表明,时间为零的Mfx与PL增强可能会改变细胞信号传导和Mfx凝块结构/重塑。最后,在猪滑车骨软骨缺损模型(t = 5周)中评估pl增强的Mfx。虽然与单独使用Mfx相比,pl处理的缺陷收缩减少,宏观外观改善,但显微ct和力学测试显示,软骨下骨重塑或修复组织刚度没有显著差异。组织学分析和分级显示,各治疗组的软骨修复质量没有显著改善,这表明尽管PL可能影响早期凝块稳定性,但其对长期组织成熟的影响仍不确定。“未来的研究需要确定基于pl的增强是否能提供持续的功能益处,并可能与其他生物或机械策略相结合。”
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引用次数: 0
Fabrication of blood capillary microtissues without fibroblast support via growth factors and matrix stiffness modulation 通过生长因子和基质刚度调节制备无成纤维细胞支持的毛细血管微组织。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-10-21 DOI: 10.1039/D5BM00981B
He Li, Fiona Louis and Michiya Matsusaki

The cells co-culture approach, involving endothelial cells and supporting stromal cells, such as fibroblasts, is commonly used for engineering microvascular networks. While this approach effectively promotes vascular morphogenesis through paracrine signaling and matrix remodeling, it often leads to excessive fibroblast proliferation. This uncontrolled growth can disrupt the structural organization of the developing vasculature, making it challenging to achieve reproducible and physiologically relevant microtissue architectures. In this work, we introduce an alternative monoculture method that uses only endothelial cells (HUVECs) in a fibrin gel matrix. To promote the formation of structured capillary-like networks without stromal support, we optimized vasculogenesis by supplementing exogenous vascular endothelial growth factor (VEGF), fine-tuning matrix stiffness, and applying it in a hypoxic environment (1% O2). This approach was also applied to brain microvascular endothelial cells (BMEC) and liver sinusoidal endothelial cells (SEC). This innovation addresses the limitations of traditional methods, overcomes rapid matrix degradation caused by fibroblast-mediated remodeling, identifies ∼2.56 kPa as the optimal stiffness for blood capillary growth, and demonstrates that capillary development is significantly enhanced at VEGF concentrations above 50 ng ml−1.

细胞共培养方法,包括内皮细胞和支持基质细胞,如成纤维细胞,通常用于工程微血管网络。虽然这种方法通过旁分泌信号和基质重塑有效地促进血管形态发生,但往往导致成纤维细胞过度增殖。这种不受控制的生长可以破坏正在发育的脉管系统的结构组织,使其难以实现可复制和生理相关的微组织结构。在这项工作中,我们介绍了一种替代的单一培养方法,该方法仅使用纤维蛋白凝胶基质中的内皮细胞(HUVECs)。为了在没有基质支持的情况下促进结构化毛细血管样网络的形成,我们通过补充外源性血管内皮生长因子(VEGF)、微调基质刚度并将其应用于低氧环境(1% O2)来优化血管发生。该方法也适用于脑微血管内皮细胞(BMEC)和肝窦内皮细胞(SEC)。这一创新解决了传统方法的局限性,克服了由成纤维细胞介导的重塑引起的基质快速降解,确定了2.56 kPa为毛细血管生长的最佳刚度,并证明了VEGF浓度高于50 ng ml-1时毛细血管发育显著增强。
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引用次数: 0
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