Materials Today Bio最新文献

A paradigm shift from penetration: Material-based solutions for multidimensional spatiotemporal, hypoxic, and optical challenges in cutaneous photodynamic therapy 从穿透的范式转变：皮肤光动力治疗中多维时空、缺氧和光学挑战的基于材料的解决方案

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-29 DOI: 10.1016/j.mtbio.2026.102872

Xun Feng , Hua Fan , Lubin Zhou , Zhilong Zhao , Mu Yang , Xinxing Sun , Yang Chen

Despite considerable advancements in pharmaceutical strategies (e.g., nanocarriers, physical enhancement) to overcome the skin barrier for topical photodynamic therapy (PDT), clinical translation remains impeded by unresolved challenges. While previous reviews have predominantly focused on enhancing photosensitizer permeation, this work shifts the paradigm to systematically address three critical yet under-reviewed barriers: insufficient spatiotemporal precision in photosensitizer delivery, hypoxia-induced therapeutic resistance, and inefficient photon utilization. This review critically evaluated the transformative evolution from conventional formulations toward “smart” therapeutic architectures, presenting a coherent framework of material-based solutions engineered to overcome these specific challenges: (1) depth-resolved, stimuli-responsive, and molecular-targeted release mechanisms; (2) transdermal oxygen self-replenishing systems (e.g., catalase-mimetic nanomaterials or perfluorocarbon-based reservoirs); and (3) synergistic optical components to enhance photon utilization, including tissue optical clearing agents, light-guiding channels, and multifunctional light-responsive platforms. These integrated strategies enable the dynamic synchronization of photosensitizer bioavailability with pathological microenvironmental demands, allowing precise modulation across spatial, temporal, and dosage dimensions. Furthermore, we incorporated an analysis of commercially available and clinically investigated photosensitizers, providing critical context for the current state and future trajectory of the field. By bridging interdisciplinary insights from materials science, drug delivery, and photobiology, this work outlines a transformative roadmap for next-generation, precision-based dermatological therapies, marking a clear departure from penetration-centric approaches.

尽管在克服局部光动力治疗（PDT）的皮肤屏障的药物策略（例如，纳米载体，物理增强）取得了相当大的进步，但临床转化仍然受到未解决的挑战的阻碍。虽然以前的综述主要集中在增强光敏剂的渗透，但这项工作将范式转移到系统地解决三个关键但尚未得到充分研究的障碍：光敏剂递送的时空精度不足，缺氧诱导的治疗抗性和低效的光子利用。这篇综述批判性地评估了从传统配方到“智能”治疗架构的变革演变，提出了一个基于材料的解决方案的连贯框架，旨在克服这些具体挑战：(1)深度解决、刺激响应和分子靶向释放机制；(2)透皮氧气自我补充系统（例如，模拟过氧化氢酶的纳米材料或全氟碳基储氧器）；(3)增强光子利用的协同光学元件，包括组织光清除剂、光导通道和多功能光响应平台。这些综合策略使光敏剂的生物利用度与病理微环境需求动态同步，允许在空间、时间和剂量维度上进行精确调节。此外，我们结合了对市售光敏剂和临床研究光敏剂的分析，为该领域的现状和未来发展轨迹提供了关键的背景。通过弥合材料科学、药物输送和光生物学的跨学科见解，这项工作概述了下一代基于精确的皮肤疗法的变革路线图，标志着与以渗透为中心的方法的明显背离。

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引用次数: 0

NIR-II imaging-guided nanoplatform for synergistic mitochondria-targeted pyroptosis and macrophage reprogramming immunotherapy NIR-II成像引导纳米平台协同线粒体靶向焦亡和巨噬细胞重编程免疫治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-27 DOI: 10.1016/j.mtbio.2026.102860

Di Zhang , Xu He , Kannappan Vinodh , Zhehan Yao , Wanyu Wei , Jingxiang Liang , Ningbo Li , Zhifang Wu , Sijin Li

Cancer immunotherapy has revolutionized modern oncology by mobilizing the body’s immune system, yet its efficacy remains severely limited in immunologically “cold” tumors, which are defined by poor immune infiltration and low tumor immunogenicity. Here, we report a multi-functional nanoplatform that integrates a new second near-infrared (NIR-II) aggregation-induced emission luminogen (AIEgen), a mitochondria-targeted lonidamine prodrug, and cryo-shocked M1 macrophage membranes (CSMs) to achieve synergistic tumor microenvironment (TME) reprogramming and precision image-guided immunotherapy. The bright NIR-II AIEgen enables high-resolution fluorescence and photoacoustic imaging for real-time tumor visualization and photothermal therapy. The prodrug LND-1-PEG-24, cleavable by TME-overexpressed cathepsin B, preferentially accumulates in mitochondria to trigger caspase-3/GSDME-mediated pyroptosis, leading to the release of danger-associated molecular patterns that markedly enhance tumor immunogenicity. Simultaneously, CSMs promote durable polarization of tumor-associated macrophages (TAMs) toward the tumoricidal M1 phenotype via the TLR2/MAPK pathway, thereby alleviating TME immunosuppression. In tumor-bearing mice, this nanoplatform synergistically enhances cytotoxic T cell infiltration, reverses immune suppression, and effectively inhibits both primary tumor growth and metastatic progression through the activation of systemic antitumor immunity. This work establishes a versatile strategy that unifies NIR-II phototheranostics, mitochondria-targeting pyroptosis, and TAM reprogramming, providing a robust and targeted approach for cancer immunotherapy.

癌症免疫疗法通过调动人体的免疫系统，使现代肿瘤学发生了革命性的变化，但在免疫“冷”肿瘤中，其疗效仍然受到严重限制，这种肿瘤的免疫浸润性差，肿瘤免疫原性低。在这里，我们报道了一个多功能纳米平台，该平台集成了新的第二种近红外（NIR-II）聚集诱导发射发光原（AIEgen），线粒体靶向lonidamine前药和低温冲击M1巨噬细胞膜（cms），以实现协同肿瘤微环境（TME）重编程和精确图像引导免疫治疗。明亮的NIR-II AIEgen可实现高分辨率荧光和光声成像，用于实时肿瘤可视化和光热治疗。前药LND-1-PEG-24可被tme过表达的组织蛋白酶B切割，优先在线粒体中积累，触发caspase-3/ gsdme介导的焦亡，导致释放危险相关的分子模式，显著增强肿瘤的免疫原性。同时，csm通过TLR2/MAPK通路促进肿瘤相关巨噬细胞（tam）向肿瘤杀伤M1表型持久极化，从而减轻TME免疫抑制。在荷瘤小鼠中，该纳米平台协同增强细胞毒性T细胞浸润，逆转免疫抑制，并通过激活全身抗肿瘤免疫有效抑制原发肿瘤生长和转移进展。这项工作建立了一种统一NIR-II光治疗、线粒体靶向焦亡和TAM重编程的通用策略，为癌症免疫治疗提供了一种强大的靶向方法。

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引用次数: 0

Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems 基于天然生物聚合物的纳米药物输送系统穿透血脑屏障及治疗脑病的研究进展

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-25 DOI: 10.1016/j.mtbio.2026.102849

Lijing Qin , Xiu Wang , Tongjuan Liang , Yongyi Bi , Zhijun Guo , Wenzhong Li , Wanjun Liang

Brain diseases are one of the most critical threats to human health. The blood-brain barrier (BBB) prevents drugs from entering the brain, rendering standard treatments for neurological illnesses ineffective. In recent years, there has been an increase in interest in nanotechnology-based research to develop innovative drug delivery systems (NDDS) for drug loading, BBB penetration, and precision delivery to diseased areas. Nanocarriers made from natural biomaterials, in particular, solve the drawbacks of standard nanocarriers, such as low stability and inadequate targeting, while simultaneously providing benefits such as simplicity of modification and good biodegradability. This review focuses on the most recent advances in NDDS based on natural biomaterials for overcoming the BBB in treating brain diseases, with a particular emphasis on the methods and mechanisms by which natural biopolymers—such as polysaccharides, peptides, and polynucleotides—break through the BBB and enhance brain-targeted delivery. We explore current challenges and future application prospects of natural biopolymers in permeable nanomedicine delivery systems for the BBB, aiming to provide key insights for advancing cross-BBB delivery platforms toward smarter, multifunctional development, subsequent research, and translational applications.

脑部疾病是对人类健康最严重的威胁之一。血脑屏障（BBB）阻止药物进入大脑，使得神经系统疾病的标准治疗无效。近年来，人们对基于纳米技术的研究越来越感兴趣，以开发创新的药物递送系统（NDDS），用于药物装载，血脑屏障渗透和精确递送到患病区域。特别是由天然生物材料制成的纳米载体，解决了标准纳米载体稳定性低、靶向性不足等缺点，同时具有修饰简单、生物降解性好等优点。本文综述了基于天然生物材料的抗脑屏障药物治疗脑疾病的最新进展，重点介绍了天然生物聚合物（如多糖、多肽和多核苷酸）突破脑屏障并增强脑靶向递送的方法和机制。我们探讨了天然生物聚合物在血脑屏障可渗透纳米药物递送系统中的当前挑战和未来应用前景，旨在为推动跨血脑屏障递送平台朝着更智能、多功能的发展、后续研究和转化应用提供关键见解。

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引用次数: 0

Nanozyme for precision treatment of hepatocellular carcinoma 纳米酶用于肝癌的精准治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-24 DOI: 10.1016/j.mtbio.2026.102840

Shu Feng , Ying Xuan , Hong Jin , Meng Cui , Xinyue Meng , Jun Liao , Jianwei Feng

Hepatocellular carcinoma (HCC) remains a formidable challenge due to profound heterogeneity, recurrence, and pervasive therapeutic resistance, creating a significant unmet clinical need. Engineered nanozymes, nanomaterials with intrinsic catalytic activities, have emerged as a transformative paradigm. Unlike passive nanocarriers, nanozymes function as active therapeutic agents. Their prowess is predicated on catalytically manipulating the tumor microenvironment (TME), enabling localized ROS generation, inducing regulated cell death, and remodeling the immunosuppressive TME. This review systematically delineates the principles and potential of nanozyme strategies for HCC, focusing on catalytic therapy, nanozyme-enhanced immunotherapy, photothermal therapy, and integrated combination platforms, highlighting their capacity for synergistic antitumor effects. The review also critically discusses formidable challenges spanning metabolic heterogeneity, TME-driven immunosuppression, and biocompatibility hurdles that impede clinical translation. This work provides critical insights for the rational design of next-generation nanozymes and accelerating their integration into future multidisciplinary HCC treatment frameworks.

肝细胞癌（HCC）由于其严重的异质性、复发性和普遍的治疗耐药性，仍然是一个巨大的挑战，创造了一个重要的未满足的临床需求。工程纳米酶，具有内在催化活性的纳米材料，已经成为一种变革范例。与被动的纳米载体不同，纳米酶作为主动治疗剂发挥作用。他们的能力是基于催化操纵肿瘤微环境（TME），使局部ROS生成，诱导调节细胞死亡，并重塑免疫抑制的TME。本文系统地阐述了纳米酶治疗HCC的原理和潜力，重点介绍了催化治疗、纳米酶增强免疫治疗、光热治疗和综合联合平台，强调了它们的协同抗肿瘤作用。该综述还批判性地讨论了代谢异质性、tme驱动的免疫抑制和阻碍临床转化的生物相容性障碍等巨大挑战。这项工作为下一代纳米酶的合理设计提供了重要的见解，并加速了它们与未来多学科HCC治疗框架的整合。

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引用次数: 0

Photocrosslinkable lung dECM hydrogels promote stiffness-dependent lung cancer growth and chemoresistance 光交联肺dECM水凝胶促进僵硬依赖性肺癌生长和化疗耐药

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-24 DOI: 10.1016/j.mtbio.2026.102838

Luke Hipwood , Minne Dekker , Dietmar W. Hutmacher , Christoph Meinert , Jacqui A. McGovern

Decellularized extracellular matrices (dECMs) are promising biomaterials for generating tissue-specific in vitro models due to their organotypic extracellular matrix (ECM) protein profiles compared to natural and synthetic alternatives. However, most dECM-based hydrogels rely on collagen fibrillogenesis, resulting in limited mechanical tuneability and cell instructivity. Here, we developed LungMA, a photocrosslinkable, methacrylated lung dECM hydrogel engineered for precise stiffness modulation and tissue-specific lung cancer modelling. The decellularization process removed >99 % of native DNA, ensuring minimal cellular remnants while preserving key ECM components including laminin-332, collagen VI, and heparan sulfate proteoglycan 2 (HSPG2). Methacrylation and photoinitiation enabled formation of stable LungMA hydrogels with tunable stiffnesses ranging from 1 kPa (healthy lung) to 4 kPa (fibrotic lung).

Using A549 non-small-cell lung cancer (NSCLC) cells, we demonstrated that matrix composition and stiffness influenced cell morphology, proliferation, and drug response. Soft LungMA (1 kPa) promoted motile, sheet-like cellular organization, whereas stiff LungMA (>4 kPa) induced compact spheroids associated with chemoresistance. Increasing matrix stiffness resulted in an increase in doxorubicin IC₅₀ from 0.40 μM (soft LungMA) to 1.23 μM (stiff LungMA), and cisplatin IC₅₀ from 0.03 μM to 8.34 μM, reflecting clinical observations where fibrosis correlates with poor prognosis.

In contrast, gelatin methacryloyl (GelMA) and basement membrane extract (BME)-based hydrogels failed to induce these stiffness-dependent effects during cisplatin treatment underscoring the instructive role of lung-specific ECM components and matrix stiffness on chemotherapeutic outcomes.

LungMA provides a physiologically relevant, mechanically tunable, lung-specific platform that replicates in vivo-like cancer phenotypes and drug responses. This work supports the application of LungMA for oncology research, disease modelling, and high-throughput drug screening as a clinically relevant, non-animal alternative for lung cancer studies.

与天然和合成替代品相比，脱细胞细胞外基质（decm）具有器官型细胞外基质（ECM）蛋白质谱，是一种很有希望用于生成组织特异性体外模型的生物材料。然而，大多数基于decm的水凝胶依赖于胶原纤维形成，导致有限的机械可调性和细胞指导性。在这里，我们开发了LungMA，一种光交联的甲基丙烯酸化肺dECM水凝胶，用于精确的刚度调节和组织特异性肺癌建模。脱细胞过程去除了99% %的天然DNA，确保了最小的细胞残留物，同时保留了关键的ECM成分，包括层粘连蛋白332、胶原VI和硫酸肝素蛋白多糖2 （HSPG2）。甲基丙烯酸基化和光起始使形成稳定的LungMA水凝胶，其硬度可调，范围从1 kPa（健康肺）到4 kPa（纤维化肺）。使用A549非小细胞肺癌（NSCLC）细胞，我们证明了基质组成和硬度影响细胞形态、增殖和药物反应。软LungMA（1 kPa）促进运动，片状细胞组织，而硬LungMA （>4 kPa）诱导致密球体，与化学耐药相关。增加基质刚度导致阿霉素IC50从0.40 μM（软肺ma）增加到1.23 μM（硬肺ma），顺铂IC50从0.03 μM增加到8.34 μM，反映了纤维化与不良预后相关的临床观察。相比之下，明胶甲基丙烯酰（GelMA）和基膜提取物（BME）为基础的水凝胶在顺铂治疗期间未能诱导这些刚度依赖效应，这强调了肺特异性ECM成分和基质刚度对化疗结果的指导作用。LungMA提供了一个生理相关的、机械可调的、肺特异性的平台，可以复制体内样癌症表型和药物反应。这项工作支持将lunma应用于肿瘤研究、疾病建模和高通量药物筛选，作为肺癌研究的临床相关、非动物替代方法。

{"title":"Photocrosslinkable lung dECM hydrogels promote stiffness-dependent lung cancer growth and chemoresistance","authors":"Luke Hipwood , Minne Dekker , Dietmar W. Hutmacher , Christoph Meinert , Jacqui A. McGovern","doi":"10.1016/j.mtbio.2026.102838","DOIUrl":"10.1016/j.mtbio.2026.102838","url":null,"abstract":"<div><div>Decellularized extracellular matrices (dECMs) are promising biomaterials for generating tissue-specific <em>in vitro</em> models due to their organotypic extracellular matrix (ECM) protein profiles compared to natural and synthetic alternatives. However, most dECM-based hydrogels rely on collagen fibrillogenesis, resulting in limited mechanical tuneability and cell instructivity. Here, we developed LungMA, a photocrosslinkable, methacrylated lung dECM hydrogel engineered for precise stiffness modulation and tissue-specific lung cancer modelling. The decellularization process removed >99 % of native DNA, ensuring minimal cellular remnants while preserving key ECM components including laminin-332, collagen VI, and heparan sulfate proteoglycan 2 (HSPG2). Methacrylation and photoinitiation enabled formation of stable LungMA hydrogels with tunable stiffnesses ranging from 1 kPa (healthy lung) to 4 kPa (fibrotic lung).</div><div>Using A549 non-small-cell lung cancer (NSCLC) cells, we demonstrated that matrix composition and stiffness influenced cell morphology, proliferation, and drug response. Soft LungMA (1 kPa) promoted motile, sheet-like cellular organization, whereas stiff LungMA (>4 kPa) induced compact spheroids associated with chemoresistance. Increasing matrix stiffness resulted in an increase in doxorubicin IC<sub>50</sub> from 0.40 μM (soft LungMA) to 1.23 μM (stiff LungMA), and cisplatin IC<sub>50</sub> from 0.03 μM to 8.34 μM, reflecting clinical observations where fibrosis correlates with poor prognosis.</div><div>In contrast, gelatin methacryloyl (GelMA) and basement membrane extract (BME)-based hydrogels failed to induce these stiffness-dependent effects during cisplatin treatment underscoring the instructive role of lung-specific ECM components and matrix stiffness on chemotherapeutic outcomes.</div><div>LungMA provides a physiologically relevant, mechanically tunable, lung-specific platform that replicates <em>in vivo</em>-like cancer phenotypes and drug responses. This work supports the application of LungMA for oncology research, disease modelling, and high-throughput drug screening as a clinically relevant, non-animal alternative for lung cancer studies.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102838"},"PeriodicalIF":10.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing polysaccharide-mediated biomineralization for advanced bone tissue engineering 利用多糖介导的生物矿化用于高级骨组织工程

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-23 DOI: 10.1016/j.mtbio.2026.102846

Huxin Tang , Mingyang Hu , Xinying Huang , Jianan Chen , Yesheng Jin , Shuo Chen , Ke Li , Yong Xu

Biomineralization is a critical process wherein organisms form mineral composites via organic-inorganic synergistic interactions, which are essential for maintaining and repairing bone tissue homeostasis. Polysaccharides, as a class of natural biological macromolecules, play a crucial role in regulating biomineralization processes. This may be ascribed to their distinctive physical and chemical characteristics, in addition to their biological functions. These molecules effectively alter the crystalline structure and mechanical attributes of minerals like hydroxyapatite by adjusting ion levels, supplying sites for nucleation during mineral formation, and interacting with other biomolecules such as collagen to direct the deposition of minerals. Chitosan, alginate, hyaluronic acid, and sulfated polysaccharides have shown significant biomimetic properties through the creation of biomimetic scaffolds, improvement of cell attachment and differentiation, and facilitation of bone defect healing. This article systematically reviews the molecular mechanisms of polysaccharides in biomineralization and discusses their applications in bone tissue engineering from a biomineralization perspective, thereby offering novel insights for clinical treatment.

生物矿化是生物体通过有机-无机协同作用形成矿物复合材料的关键过程，这对于维持和修复骨组织稳态至关重要。多糖作为一类天然生物大分子，在调节生物矿化过程中起着至关重要的作用。这可能是由于它们独特的物理和化学特性，以及它们的生物功能。这些分子通过调节离子水平，在矿物形成过程中为成核提供位置，并与其他生物分子（如胶原蛋白）相互作用来指导矿物的沉积，从而有效地改变矿物（如羟基磷灰石）的晶体结构和力学属性。壳聚糖、海藻酸盐、透明质酸和硫酸多糖通过构建仿生支架，改善细胞附着和分化，促进骨缺损愈合，显示出显著的仿生特性。本文系统综述了多糖生物矿化的分子机制，并从生物矿化的角度探讨了多糖在骨组织工程中的应用，从而为临床治疗提供新的思路。

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引用次数: 0

Unveiling aucubin-mediated inhibition of PANoptosis in lower limb ischemia-reperfusion injury with a near-infrared H2O2 fluorogenic probe 用近红外H2O2荧光探针揭示红桃素介导的下肢缺血再灌注损伤PANoptosis的抑制作用

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-23 DOI: 10.1016/j.mtbio.2026.102845

Tang Deng , Zhanli Peng , Jinxi Liang , Qinghui Kan , Jin Peng , Zhihao Zhou , Lin Huang , Heng Liu , Guiyun Jin , Chen Yao

Although reactive oxygen species (ROS)-mediated PANoptosis plays a pivotal role in the pathological dysfunction of lower limb ischemia/reperfusion injury (LL-IRI), its exact mechanism remains unclear. Real-time detection of H₂O₂ will help to reveal the complicated relationship between ROS, PANoptosis and LL-IRI. In this work, we designed and synthesized a novel near-infrared fluorogenic (NIRF) probe, BFP-H₂O₂, which exhibited a pronounced fluorescence-enhanced response to H₂O₂ at 650 nm. BFP-H₂O₂ was successfully applied to a TAK1i/LPS-induced PANoptosis cell model, revealing up-regulation of H₂O₂ during PANoptosis. To the best of our knowledge, there were no suitable chemical tools available for high-throughput screening of anti-PANoptosis compounds from Plantagodepressa Willd (PW). Leveraging BFP-H₂O₂, aucubin (AU) from PW was identified for the first time as the most promising anti-PANoptosis active ingredient. Additionally, BFP-H₂O₂ enabled visual imaging of the dynamic changes of H₂O₂ in the LL-IRI mice model. Particularly importantly, it was confirmed that AU could effectively inhibit H₂O₂-mediated oxidative stress and attenuate PANoptosis in gastrocnemius muscle tissues during LL-IRI. This work not only afforded a reliable chemical tool for screening anti-PANoptosis drugs, but also further elucidated the mechanism of PANoptosis and LL-IRI and advanced the development of therapeutic drugs for PANoptosis-related diseases.

虽然活性氧（ROS）介导的PANoptosis在下肢缺血再灌注损伤（LL-IRI）的病理功能障碍中起关键作用，但其确切机制尚不清楚。实时检测H2O2有助于揭示ROS、PANoptosis和LL-IRI之间的复杂关系。在这项工作中，我们设计并合成了一种新型的近红外荧光（NIRF）探针BFP-H2O2，该探针在650 nm处对H2O2表现出明显的荧光增强响应。bbp -H2O2成功应用于TAK1i/ lps诱导的PANoptosis细胞模型，揭示了PANoptosis过程中H2O2的上调。据我们所知，目前还没有合适的化学工具用于高通量筛选Plantagodepressa Willd （PW）中抗panoptosis化合物。利用BFP-H2O2，首次从PW中鉴定出aucubin （AU）是最有前途的抗panoptosis活性成分。此外，BFP-H2O2还能对LL-IRI小鼠模型中H2O2的动态变化进行视觉成像。特别重要的是，研究证实了AU能有效抑制h2o2介导的氧化应激，减轻LL-IRI过程中腓肠肌组织的PANoptosis。这项工作不仅为筛选抗PANoptosis药物提供了可靠的化学工具，而且还进一步阐明了PANoptosis和LL-IRI的机制，推动了PANoptosis相关疾病治疗药物的开发。

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引用次数: 0

Bioprinting and assembly of organ building blocks for tissue engineering applications 用于组织工程应用的生物打印和器官构建块组装

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-22 DOI: 10.1016/j.mtbio.2026.102842

Jae-Hun Kim , Guolong Jin , Jaehyeon Kim , Chanhyeock Kim , Chanhan Kang , Sunwoo Lee , Jin-Hyung Shim , Won-Soo Yun , Songwan Jin

Damage or functional failure of vital organs remains a major clinical challenge, while the availability of donor organs for transplantation is severely limited. As a result, tissue engineering has emerged as a promising strategy for organ replacement; however, conventional top-down tissue engineering, which employs scaffolds to provide three-dimensional growth environments, cannot ensure precise cell positioning, restricting its applicability to complex and heterogeneous tissues. In contrast, bottom-up strategies that assemble spheroids or organoids as modular building blocks offer a more effective route to organ-like constructs. Nevertheless, they suffer from low reproducibility because of spontaneous cell self-assembly. Three-dimensional bioprinting provides a promising solution for the reproducible fabrication of multicellular organ building blocks (OBBs). At the same time, while extrusion-based bioprinting offers high reproducibility, its limited dimensional accuracy has restricted its use for fabricating OBBs that require both precise microarchitectures and reliable assembly. Here, we address this limitation by introducing a strategy in which bioinks are directly bioprinted within three-dimensionally printed molds, enabling the formation of OBBs with well-defined geometries and controlled spatial organization. By combining mold-guided bioprinting with multimaterial preset extrusion, we demonstrated the fabrication of heterogeneous OBBs with microscale architectures while preserving the modularity essential for bottom-up assembly. This approach resolves the conventional trade-off between structural precision and assembly-based scalability, allowing the construction of large tissue constructs with hierarchical vascular networks. Overall, this work presents a 3D bioprinting-based OBB fabrication strategy that integrates precision manufacturing with bottom-up tissue assembly, offering a reproducible and scalable framework for bioartificial organ engineering.

重要器官的损伤或功能衰竭仍然是一个重大的临床挑战，而可供移植的供体器官的可用性严重有限。因此，组织工程已经成为一种很有前途的器官替代策略；然而，传统的自顶向下组织工程采用支架提供三维生长环境，无法保证精确的细胞定位，限制了其对复杂异质组织的适用性。相比之下，自下而上的策略将球体或类器官组装为模块构建块，为构建类器官结构提供了更有效的途径。然而，由于自发的细胞自组装，它们的可重复性较低。三维生物打印为多细胞器官构建块（OBBs）的可重复性制造提供了一个有前途的解决方案。与此同时，虽然基于挤压的生物打印具有高再现性，但其有限的尺寸精度限制了其用于制造需要精确微结构和可靠组装的obb的使用。在这里，我们通过引入一种策略来解决这一限制，在这种策略中，生物墨水直接在三维打印模具中进行生物打印，从而形成具有明确几何形状和可控空间组织的obb。通过将模具引导生物打印与多材料预设挤出相结合，我们展示了具有微尺度结构的异质obb的制造，同时保留了自下而上组装所必需的模块化。这种方法解决了结构精度和基于装配的可扩展性之间的传统权衡，允许构建具有分层血管网络的大型组织结构。总的来说，这项工作提出了一种基于3D生物打印的OBB制造策略，该策略将精密制造与自下而上的组织组装相结合，为生物人工器官工程提供了可复制和可扩展的框架。

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引用次数: 0

Urinary microenvironment-degradable nanocapsules for traceable therapy of diabetic nephropathy 尿微环境可降解纳米胶囊用于糖尿病肾病的可追溯治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-22 DOI: 10.1016/j.mtbio.2026.102833

Ru Feng , Tao Yue , Xuhui Zhao , Jie Dong , Jin Zhang , Xiaoyang Peng , Huifang Zhao , Jinghua Sun , Ruiping Zhang

Diabetic nephropathy (DN) is a serious complication of diabetes and a leading cause of end-stage renal disease. Current treatments using anti-inflammatory, antioxidant, and antifibrotic drugs are limited by rapid systemic clearance and poor renal retention. Here, we developed a urine-microenvironment responsive nanocapsule, MNP-THA@MnCaP, composed of a MnCaP nanoshell co-loaded with functionalized melanin (MNP) nanoparticles and thalidomide (THA) for synergistic therapy of DN. The nanocapsules preferentially accumulate in the kidneys via passive targeting and degrade under acidic urinary conditions, enabling controlled release of therapeutic agents. In vitro, MNP-THA@MnCaP alleviated oxidative stress, suppressed epithelial-mesenchymal transition, and reduced apoptosis in renal tubular cells. In vivo, the formulation targeted DN kidneys, attenuated oxidative injury, inflammation, and fibrosis, and restored renal function. Moreover, the released Mn²⁺ allowed T₁-weighted magnetic resonance imaging, while MNP supported photoacoustic imaging, facilitating real-time tracking of the treatment process. With excellent biocompatibility and biodegradability, MNP-THA@MnCaP represents a promising theranostic platform with strong translational potential for DN treatment.

糖尿病肾病（DN）是糖尿病的严重并发症和终末期肾脏疾病的主要原因。目前使用抗炎、抗氧化和抗纤维化药物的治疗受到快速全身清除和肾潴留不良的限制。在这里，我们开发了一种尿微环境响应纳米胶囊MNP-THA@MnCaP，由MnCaP纳米壳与功能化黑色素（MNP）纳米颗粒和沙利度胺（THA）共同负载，用于协同治疗DN。纳米胶囊通过被动靶向在肾脏中优先积累，并在酸性尿液条件下降解，从而控制治疗剂的释放。在体外，MNP-THA@MnCaP可减轻肾小管细胞氧化应激，抑制上皮-间质转化，减少细胞凋亡。在体内，该制剂靶向DN肾脏，减轻氧化损伤、炎症和纤维化，恢复肾功能。此外，释放的Mn2+允许进行t1加权磁共振成像，而MNP支持光声成像，便于实时跟踪处理过程。MNP-THA@MnCaP具有良好的生物相容性和可生物降解性，是一个很有前途的治疗平台，具有很强的DN治疗转化潜力。

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引用次数: 0

Sequential delivery of sinigrin and dabigatran by an in situ self-stabilizing dynamic hydrogel attenuates intervertebral disc degeneration 通过原位自稳定动态水凝胶连续给药单宁和达比加群可减轻椎间盘退变

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-22 DOI: 10.1016/j.mtbio.2026.102827

Rui Hu , Kaiwen Liu , Wenzhao Wang , Wencan Zhang , Liang Wang , Yuanqiang Zhang , Hecheng Ma , Menglin Cong , Chuanxi Chi , Jiankang Cao , Baoliang Zhang , Liang Liu , Qunbo Meng , Xiangzhen Kong , Bin Shi , Liming Li , Lei Cheng , Zhijian Wei

Intervertebral disc degeneration (IDD) is characterized by an imbalance between nucleus pulposus catabolism and anabolism, driven by metabolic dysfunction of nucleus pulposus cells (NPCs) and a chronic inflammatory microenvironment. Effective treatments for IDD are lacking. Here, we report an injectable hydrogel that achieves reactive oxygen species (ROS)-triggered self-stabilization within the degenerative microenvironment for adaptive intradiscal therapy. The CAD hydrogel is constructed from chitosan-phenylboronic acid (CS-PBA), aldehyde-β-cyclodextrin (A-β-CD), and hyaluronic acid-dopamine (HA-DA), forming a dynamic multinetwork. The dopamine moieties are preorganized within the network via both boronate ester bonds and host‒guest interactions with β-CD. Upon encountering pathological ROS in the oxidative IDD microenvironment, the cleavage of boronate esters triggers the release of sinigrin (SIN). Moreover, in situ polymerization of the dopamine moieties occurs simultaneously, which is facilitated by the spatial confinement of dopamine by β-CD. Polymerization converts the dynamic network into a covalently stabilized matrix, effectively self-solidifying the hydrogel to counteract mechanical decay and enabling the sustainable release of dabigatran (DAB) encapsulated in β-CD. This process ensures long-term structural support while enabling intelligent dual drug delivery. In a puncture-induced IDD model, the hydrogel demonstrated significant efficacy. In vitro, the dual-drug-loaded DS@CAD hydrogel mitigated NPC inflammatory catabolism and promoted anabolism. Mechanistically, the rapid release of SIN attenuated inflammation by targeting MAPK signalling, while sustained DAB release inhibited inflammation via RELA and promoted extracellular matrix anabolism by activating AMPK. This reconfigurable hydrogel platform offers an innovative strategy for developing next-generation biomaterials that respond to complex disease microenvironments for adaptive therapy.

椎间盘退变（IDD）以髓核分解代谢和合成代谢失衡为特征，由髓核细胞（NPCs）代谢功能障碍和慢性炎症微环境驱动。缺乏对缺碘症的有效治疗。在这里，我们报告了一种可注射的水凝胶，可在退行性微环境中实现活性氧（ROS）触发的自稳定，用于适应性椎间盘内治疗。CAD水凝胶由壳聚糖-苯硼酸（CS-PBA）、醛-β-环糊精（A-β-CD）和透明质酸-多巴胺（HA-DA）构成，形成动态多网络。多巴胺部分通过硼酸酯键和与β-CD的主客体相互作用在网络中预先组织。在氧化IDD微环境中遇到病理性ROS时，硼酸酯的裂解触发sinigin （SIN）的释放。此外，多巴胺部分的原位聚合同时发生，这是由于β-CD对多巴胺的空间限制所促进的。聚合将动态网络转化为共价稳定的基质，有效地自固化水凝胶以抵消机械衰变，并使包裹在β-CD中的达比加群（DAB）可持续释放。这一过程确保了长期的结构支持，同时实现了智能双重给药。在针刺诱导的IDD模型中，水凝胶显示出显著的疗效。在体外，双重药物负载DS@CAD水凝胶减轻鼻咽癌炎症分解代谢并促进合成代谢。从机制上讲，SIN的快速释放通过靶向MAPK信号来减轻炎症，而DAB的持续释放通过RELA抑制炎症，并通过激活AMPK促进细胞外基质合成代谢。这种可重构的水凝胶平台为开发下一代生物材料提供了一种创新策略，该生物材料可响应复杂的疾病微环境，用于适应性治疗。

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引用次数: 0