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RGD Modification of Poly(2-oxazoline) Cryogels: Investigation of Material Properties and Cellular Adhesion 聚(2-恶唑啉)低温材料的RGD改性:材料性能和细胞粘附性的研究。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-14 DOI: 10.1002/mabi.202500421
Tim Hoffmann, David Pretzel, Steffi Stumpf, Florian Behrendt, Michael Klein, Leon Lange, Lena-Marie Kaspar, Klaus Liefeith, Michael Gottschaldt, Ulrich S. Schubert

In this study, we demonstrate the preparation of a poly(2-oxazoline) based RGD-functionalized cryogels and cell culture studies on these cryogels. The present work also involves the investigation of cryogels with ethyl side chains (CG(B-Et-PipA)) and primary amino groups in their side chain (CG(B-Am-PipA)) which have been synthesized previously. CG(B-Am-PipA) was subsequently functionalized with a peptide containing an RGD motif (GCWGRGDSP), resulting in the formation of CG(B-Am-PipA/RGD). The coupling was verified by confocal laser-scanning microscopy (CLSM), fourier-transform infrared spectroscopy (FT-IR), high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy, and gravimetrical measurements. The degree of functionalization was found to be around 45%. The functionalized gels exhibited a change in their thermal properties, which was examined using thermogravimetric analysis (TGA). Rheological analysis was employed to study the mechanical properties and showed the formation of a stiffer material after peptide coupling. Swelling tests revealed a reduced swelling behavior for CG(B-Am-PipA/RGD). Cell biological investigations were conducted with L929 cells which were incubated with the samples CG(B-Et-PipA)RhoB, CG(B-Am-PipA)RhoB and CG(B-Am-PipA/RGD)RhoB. CLSM measurements after 0.5, 1, 2 and 6 h revealed an initial adhesion for both CG(B-Am-PipA)RhoB and CG(B-Am-PipA/RGD)RhoB, with the RGD-functionalized cryogel exhibiting the fastest cell adhesion and the most pronounced adherent phenotype, characterized by distinctly spread cell bodies as confirmed by cell area measurements. Cultivation of cells over a period of 7 days, analyzed by scanning electron microscopy (SEM), further showed pronounced cellular adhesion exclusively on CG(B-Am-PipA) and CG(B-Am-PipA/RGD).

在这项研究中,我们展示了一种基于聚(2-恶唑啉)的rgd功能化冷冻材料的制备以及这些冷冻材料的细胞培养研究。目前的工作还包括研究先前合成的具有乙基侧链(CG(B-Et-PipA))和其侧链上的初级氨基(CG(B-Am-PipA))的冷冻液。CG(B-Am-PipA)随后被含有RGD基序的肽(GCWGRGDSP)功能化,从而形成CG(B-Am-PipA/RGD)。通过共聚焦激光扫描显微镜(CLSM)、傅里叶变换红外光谱(FT-IR)、高分辨率魔角旋转(HR-MAS)核磁共振光谱(NMR)和重力测量验证了这种耦合。功能化程度约为45%。用热重分析(TGA)对功能化凝胶的热性能进行了研究。采用流变学分析方法研究了多肽偶联后材料的力学性能,并证明了多肽偶联后材料的刚性增强。肿胀试验显示CG(B-Am-PipA/RGD)的肿胀行为减少。将L929细胞与CG(B-Et-PipA)RhoB、CG(B-Am-PipA)RhoB和CG(B-Am-PipA/RGD)RhoB孵育,进行细胞生物学研究。0.5、1、2和6 h后的CLSM测量显示,CG(B-Am-PipA)RhoB和CG(B-Am-PipA/RGD)RhoB都有初始粘附,RGD功能化的冷冻凝胶表现出最快的细胞粘附速度和最明显的粘附表型,细胞面积测量证实了其明显扩散的细胞体特征。通过扫描电镜(SEM)分析,培养7天的细胞进一步显示CG(B-Am-PipA)和CG(B-Am-PipA/RGD)具有明显的细胞粘附。
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引用次数: 0
Thrombus Removal with Magnetically Actuated Micro-Transformers 用磁致微变压器去除血栓。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-14 DOI: 10.1002/mabi.202500652
Fanan Wei, Shifan Zhan, Ligang Yao, Qing Deng, Zhiwei Wu

Thrombotic disorders rank among the principal global mortality factors. Despite significant advancements in interventional therapy technologies, conventional medical robots remain constrained by rigid architectures and elevated invasiveness, leading to vascular wall stress and frictional injury. Furthermore, these systems face challenges in reconciling the flexibility necessary for untethered navigation with reliable vascular traversal. To overcome these limitations, we present a magnetically actuated Micro-transformers (MAMT) with in situ structural reconfigurability. The microrobot, constructed from shape memory polymer (SMP), leverages the magnetothermal effect of Fe3O4 magnetic nanoparticles induced by an alternating magnetic field (AMF). When the temperature surpasses the glass transition temperature (50°C) of the SMP, the robot's structure transitions from its initial rod-like form to a final helical shape. Thus, dual-mode operation is achieved: rod-shaped structures for navigation and spiral-shaped structures for thrombus fragmentation. In the MAMT fabricated in this paper, in a simulated blood environment at room temperature, structural switching could be completed within 148 ± 8 s with AMF, and its shape recovery ratio could reach 92.11%. In the simulated thrombus clearance experiments, the thrombus clearance ratio could reach 52.7%. It can reduce the risk of vascular wall injury and enhance the safety of thrombus removal, offering an innovative solution for thrombus treatment.

血栓性疾病是全球主要死亡因素之一。尽管介入治疗技术取得了重大进展,但传统的医疗机器人仍然受到刚性结构和高侵入性的限制,导致血管壁应力和摩擦损伤。此外,这些系统在协调无系绳导航所需的灵活性和可靠的血管穿越方面面临挑战。为了克服这些限制,我们提出了一种具有原位结构可重构性的磁致微变压器(MAMT)。该微型机器人由形状记忆聚合物(SMP)构成,利用了交变磁场(AMF)诱导的Fe3O4磁性纳米颗粒的磁热效应。当温度超过SMP的玻璃化转变温度(50°C)时,机器人的结构从最初的棒状形式转变为最终的螺旋形状。因此,实现了双模式操作:用于导航的杆状结构和用于血栓破碎的螺旋状结构。在本文制备的MAMT中,在室温模拟血液环境下,AMF可以在148±8 s内完成结构切换,其形状恢复率达到92.11%。在模拟血栓清除实验中,血栓清除率可达52.7%。它可以降低血管壁损伤的风险,提高血栓清除的安全性,为血栓治疗提供了创新的解决方案。
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引用次数: 0
Xanthan Gum and Tamarind Seed Polysaccharide Blend Bioinks: Toward Solving Printability-Integrity Conundrum in Extrusion Bioprinting Without a Crosslinking Agent 黄原胶和罗望子籽多糖混合生物墨水:在没有交联剂的情况下解决挤出生物打印的可打印性和完整性难题。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-14 DOI: 10.1002/mabi.202500181
Aashwini Bhavsar, Priyanka Das, Raj Lakshmi Ojha, Shalini Dasgupta, Netraj Bandawar, Sreya Gupta, Pallab Datta

Bioprinting technologies face challenges in designing bioinks that possess optimal pre- and post-bioprinting properties. In most cases, enhancing flowability to improve pre-bioprinting properties results in inferior mechanical properties of the post-printed constructs. To achieve adequate mechanical strength, physical or chemical cross-linking is used, which compromises the biocompatibility and degradability of the constructs. A xanthan gum (XG) and tamarind seed polysaccharide (TSP) blend bioink was developed to overcome these limitations. Amongst several ratios, 4XG:1TSP (4X1T) demonstrated the highest printability with accuracy >95%. Rheological investigations revealed shear thinning viscosity while the LVER and creep recovery for 4X1T (698 MPa, 97%) and 4X (624 MPa, 85%) showed suitable properties for bioprinting applications. FTIR indicated hydrogen-bonding interactions between XG and TSP, conferring structural stability to the post-printed constructs without any crosslinking agent. The constructs showed loss of microstructure after 21 days of incubation in phosphate buffer (pH 7.5) at 37°C. In vitro cytocompatibility studies with human-derived SH-SY5Y cells disclosed no significant difference between the viability of cells seeded on XG and 4X1T, or cells bioprinted with 4X1T bioinks. It is concluded that the XG-TSP blend provides a bioink with promising printability, mechanical integrity, degradability, and cytocompatibility for the fabrication of tissue engineering constructs.

生物打印技术面临着设计具有最佳生物打印前后性能的生物墨水的挑战。在大多数情况下,提高流动性以改善生物预打印性能会导致打印后结构体的机械性能下降。为了获得足够的机械强度,使用物理或化学交联,这损害了构建物的生物相容性和可降解性。黄原胶(XG)和罗望子多糖(TSP)混合生物链是为了克服这些局限性而开发的。在几个比例中,4XG:1TSP (4X1T)显示出最高的打印能力,精度达到95%。流变学研究表明,4 × 1t (698 MPa, 97%)和4X (624 MPa, 85%)的LVER和蠕变恢复性能适合生物打印应用。FTIR显示XG和TSP之间存在氢键相互作用,使打印后的结构在没有任何交联剂的情况下具有结构稳定性。在37°C的磷酸盐缓冲液(pH 7.5)中孵育21天后,这些构建体显示出微观结构的丧失。人源性SH-SY5Y细胞的体外细胞相容性研究显示,XG和4X1T上接种的细胞,以及用4X1T生物墨水打印的细胞的活力没有显著差异。结果表明,XG-TSP共混物为组织工程结构的制造提供了一种具有良好打印性、机械完整性、可降解性和细胞相容性的生物连接材料。
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引用次数: 0
From Bioactive Peptides to Transdermal Peptides: An Emerging Strategy for Revolutionizing Drug Delivery 从生物活性肽到透皮肽:一种革新药物传递的新兴策略
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-14 DOI: 10.1002/mabi.202500485
Guangpu Yang, Yixuan Li, Jingwen Tian, Wenxiu Ding, Xiuxiu Li, Xuanxuan Ma, Tao Wei, Jing Xu

Transdermal peptides, Engineered from bioactive peptides through rational sequence modification and structural optimization, transdermal peptides have emerged as a transformative strategy for enhancing the transdermal delivery of macromolecular drugs, proteins, and nucleic acids. This review outlines the structural classifications of bioactive peptides, including short, linear, cyclic, cationic, anionic, and neutral peptides, as well as their diverse biological sources. It focuses on the design principles and penetration mechanisms of transdermal peptides. These peptides interact dynamically with skin constituents, such as lipids and keratins, by fine-tuning the hydrophilic-hydrophobic balance, molecular weight, and conformational stability. This transiently disrupts the stratum corneum barrier and facilitates drug permeation via endocytosis and receptor-mediated pathways. They find applications in various pharmaceutical domains, including localized anticancer and antimicrobial therapies, as well as in cosmetics for whitening, anti-aging, and moisturizing. They are also being explored in innovative areas such as hair regeneration and wound healing. When combined with advanced delivery platforms, such as nanocarriers, microneedles, and microfluidic systems, transdermal peptides can significantly improve targeting efficacy and enable controlled release. Despite challenges related to peptide immunogenicity and scalable synthesis, the future integration of smart, stimuli-responsive technologies and artificial intelligence promises to Bioactive peptides, Skin permeation mechanisms, Skin transmission, Transdermal peptidesadvance personalized transdermal therapeutics.

透皮肽是由生物活性肽经过合理的序列修饰和结构优化改造而成的,它已成为增强大分子药物、蛋白质和核酸经皮传递的一种变革性策略。本文综述了生物活性肽的结构分类,包括短肽、线性肽、环状肽、阳离子肽、阴离子肽和中性肽,以及它们不同的生物来源。重点介绍了透皮肽的设计原理和渗透机制。这些肽通过微调亲疏水平衡、分子量和构象稳定性,与皮肤成分(如脂质和角蛋白)动态相互作用。这短暂地破坏角质层屏障,并通过内吞作用和受体介导的途径促进药物渗透。它们被应用于各种制药领域,包括局部抗癌和抗菌治疗,以及美白、抗衰老和保湿化妆品。它们也被用于创新领域,如头发再生和伤口愈合。当与先进的给药平台,如纳米载体、微针和微流体系统相结合时,透皮肽可以显著提高靶向效果并实现控释。尽管在多肽免疫原性和可扩展合成方面存在挑战,但未来智能、刺激响应技术和人工智能的整合有望在生物活性肽、皮肤渗透机制、皮肤传输、透皮肽等方面推进个性化透皮治疗。
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引用次数: 0
κ-Carrageenan Scaffolds Incorporating Hydroxyapatite-Coated Chitosan Nanoparticles for Bone Tissue Engineering and Controlled Rosuvastatin Release 羟基磷灰石包覆壳聚糖纳米颗粒的κ-卡拉胶支架用于骨组织工程和瑞舒伐他汀控制释放。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-14 DOI: 10.1002/mabi.202500428
Mohammad Salmani Mobarakeh, Monireh Kouhi, Legha Ansari, Sayedeh Boshra Sadat, Saman Savabi, Farahnaz Nejatidanesh, Rahmatollah Emadi

Current treatments for critical-sized bone defects are often ineffective, necessitating advanced biomaterial scaffolds that can address this limitation. A key challenge in developing these scaffolds is achieving sustained, localized delivery of osteoinductive drugs, which is crucial for enhancing bone tissue regeneration within the defect site. This research engineered a novel κ-carrageenan-based composite scaffold incorporating hydroxyapatite-coated chitosan nanoparticles for regulated rosuvastatin release. Chitosan nanoparticles containing rosuvastatin were synthesized using a water-in-oil emulsion method and subsequently coated with hydroxyapatite. κ-carrageenan-based scaffolds were then fabricated with varying concentrations of nanoparticles (0%, 10%, 20%, and 30%) and evaluated for their physical and mechanical properties. They were also assessed for biocompatibility, osteogenic differentiation potential, and hemocompatibility. Notably, the hydroxyapatite coating increased the size of nanoparticles and enabled a stable, long-term release of rosuvastatin. Moreover, incorporating these nanoparticles into scaffolds further enhanced the sustained release profile appropriate for long-term bone healing. Scaffolds containing 20% nanoparticles demonstrated the highest mechanical strength and were selected for cell adhesion, proliferation, and differentiation studies. Alkaline phosphatase activity and alizarin red staining confirmed the scaffolds’ ability to promote osteogenic differentiation. Hemocompatibility assessment revealed a low hemolysis percentage (< 5%) for the carrageenan-based scaffolds, indicating good blood compatibility. Overall, the developed composite scaffold exhibits promising biocompatibility and efficacy for the controlled delivery of rosuvastatin and the repair of bone defects.

目前对临界尺寸骨缺损的治疗通常是无效的,需要先进的生物材料支架来解决这一限制。开发这些支架的一个关键挑战是实现骨诱导药物的持续、局部递送,这对于增强缺损部位的骨组织再生至关重要。本研究设计了一种新型的κ-卡拉胶基复合支架,将羟基磷灰石包覆的壳聚糖纳米颗粒用于调节瑞舒伐他汀的释放。采用油包水乳化法制备瑞舒伐他汀壳聚糖纳米颗粒,并包被羟基磷灰石。然后用不同浓度的纳米颗粒(0%、10%、20%和30%)制备κ-卡拉胶基支架,并评估其物理和机械性能。同时还评估了它们的生物相容性、成骨分化潜能和血液相容性。值得注意的是,羟基磷灰石涂层增加了纳米颗粒的尺寸,并使瑞舒伐他汀稳定、长期释放。此外,将这些纳米颗粒纳入支架进一步增强了适合长期骨愈合的持续释放谱。含有20%纳米颗粒的支架表现出最高的机械强度,并被选择用于细胞粘附、增殖和分化研究。碱性磷酸酶活性和茜素红染色证实了支架促进成骨分化的能力。血液相容性评估显示,卡拉胶基支架的溶血率低(< 5%),表明血液相容性良好。总的来说,所开发的复合支架在瑞舒伐他汀的控制递送和骨缺损修复方面具有良好的生物相容性和有效性。
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引用次数: 0
Nanoformulated PDRN Improves Anti-Inflammatory and Wound Healing Activities 纳米配方PDRN提高抗炎和伤口愈合活性。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-14 DOI: 10.1002/mabi.202500373
Ji-Hye Kang, Min Jeong Jeon, Sung-Eun Kim, Won Kyung Hwang, Mi-Young Lee

Polydeoxyribonucleotide (PDRN), a bioactive DNA fragment, has been known to promote anti-inflammatory responses and wound healing primarily via adenosine A2A receptor activation. However, low molecular weight PDRN can undergo rapid degradation, limiting its sustained therapeutic efficacy. In this study, we developed a scalable method to produce high-purity, and low molecular weight PDRN (c.a. 325 bp) from calf thymus DNA via physical fragmentation. To enhance its stability and delivery, PDRN was encapsulated in poly(lactic-co-glycolic acid) (PLGA) to form PDRN/PLGA nanoparticles, yielding uniform and spherical particles (336 ± 43 nm). These nanoparticles exhibited excellent colloidal stability and biodegradability (38.3% over 14 days), with sustained PDRN release (88.39% over 14 days). Moreover, the nanoformulation effectively protected PDRN from thermal, acidic, enzymatic, and UV degradation. The PDRN/PLGA nanoparticles, which exhibited no cytotoxicity or hemolysis, demonstrated superior anti-inflammatory and wound-healing efficacy compared to free PDRN. In an in vitro lipopolysaccharide (LPS)-induced inflammatory wound model, they significantly accelerated wound closure compared to both LPS-treated and untreated controls. These results suggest that nanoformulation effectively protects low molecular weight PDRN, thereby significantly enhancing its therapeutic activity and underscore the potential of PDRN/PLGA nanoparticles as a stable and effective platform for the regeneration of skin inflammation.

聚脱氧核糖核苷酸(PDRN)是一种生物活性DNA片段,主要通过腺苷A2A受体激活来促进抗炎反应和伤口愈合。然而,低分子量的PDRN可以经历快速降解,限制了其持续的治疗效果。在这项研究中,我们开发了一种可扩展的方法,通过物理裂解从小牛胸腺DNA中生产高纯度、低分子量的PDRN(约325 bp)。为了提高PDRN的稳定性和传递性,我们将PDRN包裹在聚乳酸-羟基乙酸(PLGA)中,形成PDRN/PLGA纳米颗粒,得到均匀的球形颗粒(336±43 nm)。这些纳米颗粒具有良好的胶体稳定性和生物降解性(14天内38.3%),PDRN持续释放(14天内88.39%)。此外,纳米配方有效地保护了PDRN免受热、酸、酶和紫外线的降解。与游离PDRN相比,PDRN/PLGA纳米颗粒没有细胞毒性或溶血作用,具有更好的抗炎和伤口愈合效果。在体外脂多糖(LPS)诱导的炎症伤口模型中,与LPS处理和未处理的对照组相比,它们显著加速了伤口愈合。这些结果表明,纳米制剂可以有效地保护低分子量PDRN,从而显著增强其治疗活性,并强调了PDRN/PLGA纳米颗粒作为稳定有效的皮肤炎症再生平台的潜力。
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引用次数: 0
Issue Information: Macromol. Biosci. 1/2026 资料:宏mol。Biosci 1/2026。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-13 DOI: 10.1002/mabi.70132
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引用次数: 0
Front Cover: Comparative Physicochemical Characterization of Electrospun PCL, PLLA, and PLCL Scaffolds and Cell Responses for Tissue Engineering Applications 封面:静电纺PCL、PLLA和PLCL支架的比较物理化学特性和组织工程应用中的细胞反应
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-13 DOI: 10.1002/mabi.70144
Martyna Polak, Nagalekshmi Uma Thanu Krishnan Neela, Krzysztof Berniak, Joanna Knapczyk-Korczak, Mateusz M. Marzec, Urszula Stachewicz

This cover illustrates how electrospun polymer fiber architecture governs cell-material interactions in tissue engineering. Confocal microscopy highlights enhanced cytoskeletal spreading of osteoblasts on PLCL fibrous scaffolds. By correlating fiber morphology, surface chemistry, and mechanical properties, the study demonstrates how scaffold design directs cellular adhesion, organization, and long-term viability. More details can be found in the Research Article by Urszula Stachewicz and co-workers (DOI: 10.1002/mabi.202500564).

这个封面说明了电纺聚合物纤维结构如何在组织工程中控制细胞-材料相互作用。共聚焦显微镜显示PLCL纤维支架上成骨细胞的细胞骨架扩散增强。通过将纤维形态、表面化学和机械性能相关联,该研究展示了支架设计如何指导细胞粘附、组织和长期生存能力。更多细节可以在Urszula Stachewicz及其同事的研究文章中找到(DOI: 10.1002/mabi.202500564)。
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引用次数: 0
Ferritin-Based Pravastatin Assembly Augments Mucus Penetration and Ameliorates Acute Lung Injury Via Rho/ROCK Signaling Pathway. 基于铁蛋白的普伐他汀组装增强黏液渗透并通过Rho/ROCK信号通路改善急性肺损伤
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 DOI: 10.1002/mabi.202500549
Ting Xie, Yulu Hong, Yuan Chen, Yuteng Chu, Haotian Tan, Mingyang Zhang, Fanyu Cheng, Mengmeng Ye, Jie Shen, Yue Cai, Pengfu Liu, Xuanrong Sun

Acute lung injury (ALI) is a common respiratory disease accompanied by alveolar capillary membrane dysfunction, inflammation and alveolar fluid deposition. Currently, the primary treatment for ALI involves intravenous or oral administration of glucocorticoid drugs. However, this approach suffers from low effective drug concentrations reaching the lungs and may cause systemic toxic side effects. Therefore, there is an urgent need to develop novel therapeutic agents and optimized delivery strategies specifically tailored for ALI treatment. On one hand, pravastatin (Prv) exhibits potent anti-inflammatory and antioxidant properties and has demonstrated therapeutic efficacy in ALI treatment, positioning it as a promising drug candidate. However, its underlying mechanisms remain poorly understood. On the other hand, inhalation represents a highly promising delivery approach for ALI therapy by enhancing drug retention in the lungs. Nevertheless, this localized administration strategy still faces the challenge of mucus barrier impeding drug penetration. Herein, a ferritin-based pravastatin nanoassembly (Prv@FTn) was developed to improve the mucus-penetrating ability of Prv. In vitro and in vivo investigations revealed that Prv@FTn alleviates LPS-induced ALI symptoms through inhibition of the Rho-ROCK I/II signaling pathway. These findings suggest that mucus-penetrating Prv@FTn is a promising Rho/ROCK signaling pathway inhibitor for ALI therapy.

急性肺损伤(Acute lung injury, ALI)是一种常见的呼吸系统疾病,伴有肺泡毛细血管膜功能障碍、炎症和肺泡积液。目前,ALI的主要治疗包括静脉注射或口服糖皮质激素药物。然而,这种方法的缺点是药物到达肺部的有效浓度较低,并可能引起全身毒副作用。因此,迫切需要开发专门针对ALI治疗的新型治疗剂和优化的给药策略。一方面,普伐他汀(Prv)具有有效的抗炎和抗氧化特性,并已在ALI治疗中显示出治疗效果,使其成为一种有前景的候选药物。然而,其潜在机制仍然知之甚少。另一方面,吸入是一种非常有前途的ALI治疗方法,通过增强药物在肺部的潴留。然而,这种局部给药策略仍然面临着粘液屏障阻碍药物渗透的挑战。本文开发了一种基于铁蛋白的普伐他汀纳米组装体(Prv@FTn),以提高Prv的黏液穿透能力。体外和体内研究表明,Prv@FTn通过抑制Rho-ROCK I/II信号通路减轻lps诱导的ALI症状。这些发现表明,黏液穿透Prv@FTn是一种很有前景的用于ALI治疗的Rho/ROCK信号通路抑制剂。
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引用次数: 0
High-Throughput 3D Glioblastoma Model in Glycosaminoglycan Hydrogels for Personalized Therapeutic Screening. 糖胺聚糖水凝胶的高通量3D胶质母细胞瘤模型用于个性化治疗筛选。
IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 DOI: 10.1002/mabi.202500394
Rajvinder Kaur Trautmann, Nicholas Dennison, Kathleen McCortney, Solveig Klier, Mehmet Ilyas Cosacak, Carsten Werner, Goktug Akyoldas, Craig M Horbinski, Uwe Freudenberg, Caghan Kizil

Glioblastoma (GBM) is a devastating brain tumor with limited treatment success, partly because in vitro models poorly mimic in vivo complexity. This study introduces a high-throughput 3D culture platform utilizing modular starPEG-glycosaminoglycan (GAG) hydrogels that enable independent control of extracellular matrix (ECM) cues: stiffness, cytokine affinity, matrix metalloproteinase-responsive remodeling, and cell adhesiveness via integrin-binding RGD peptides. This platform supports encapsulation of patient-derived GBM cells, recreates physiologically relevant tumor microenvironments in 384-well plates, and enables automated drug testing on primary cells. Transcriptomic analyses show that 3D cultures recapitulate primary and recurrent GBM programs- including hypoxia-, immune-, and ECM-regulatory pathways driving growth, invasion, and resistance, without externally imposed hypoxia. The platform's versatility extends to drug screening, where single and combinatorial treatments produce reproducible cytoskeletal and transcriptomic responses. Notably, the system revealed dose-dependent reductions in invasive filaments and spheroid architecture with 5-fluorouracil/uridine and carmustine, demonstrating its potential for optimizing combinatorial therapies. This 3D model surpasses 2D cultures, capturing tumor-specific molecular programs and offering a robust tool for translational research. Despite lacking vascular or immune components, its tunability, scalability, and clinical relevance make it a strong basis for advanced co-cultures. By delivering reliable, individualized therapeutic data within a short timeframe, this model holds transformative potential for personalized GBM treatment.

胶质母细胞瘤(GBM)是一种治疗成功率有限的破坏性脑肿瘤,部分原因是体外模型难以模拟体内复杂性。本研究介绍了一种利用模块化starpeg -糖胺聚糖(GAG)水凝胶的高通量3D培养平台,该平台能够独立控制细胞外基质(ECM)信号:硬度、细胞因子亲和力、基质金属蛋白酶响应性重塑以及通过整合素结合RGD肽的细胞粘附性。该平台支持患者源性GBM细胞的包封,在384孔板中重建生理相关的肿瘤微环境,并实现原代细胞的自动化药物测试。转录组学分析表明,3D培养物概括了原发性和复发性GBM程序-包括缺氧,免疫和ecm调节途径,驱动生长,侵袭和抵抗,没有外部施加的缺氧。该平台的多功能性扩展到药物筛选,其中单一和组合治疗产生可重复的细胞骨架和转录组反应。值得注意的是,该系统显示5-氟尿嘧啶/尿嘧啶和卡莫司定的侵袭性细丝和球状结构的剂量依赖性减少,表明其优化组合治疗的潜力。这种3D模型超越了2D培养,捕获了肿瘤特异性分子程序,并为转化研究提供了一个强大的工具。尽管缺乏血管或免疫成分,但其可调节性、可扩展性和临床相关性使其成为高级共培养的坚实基础。通过在短时间内提供可靠的个性化治疗数据,该模型具有个性化GBM治疗的变革性潜力。
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Macromolecular bioscience
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