Advanced Healthcare Materials最新文献_第10页

Precisely Tailored Annulated Porphyrin with Intense NIR Absorption for Highly Efficient Photothermal Therapy and Photoacoustic Imaging. 精确定制的环状卟啉与强近红外吸收高效光热治疗和光声成像。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-13 DOI: 10.1002/adhm.202500789

Chulin Qu, Chengyan Zhao, Yingzhe Hu, Shaohai Liu, Haodong Xu, Xidan Wen, Pengfei Li, Xinhua Zhu, Fan Wu, Zhen Shen

{"title":"Precisely Tailored Annulated Porphyrin with Intense NIR Absorption for Highly Efficient Photothermal Therapy and Photoacoustic Imaging.","authors":"Chulin Qu, Chengyan Zhao, Yingzhe Hu, Shaohai Liu, Haodong Xu, Xidan Wen, Pengfei Li, Xinhua Zhu, Fan Wu, Zhen Shen","doi":"10.1002/adhm.202500789","DOIUrl":"https://doi.org/10.1002/adhm.202500789","url":null,"abstract":"Constructing near-infrared (NIR) phototherapy agents with good biosafety is highly desirable for cancer therapy. Herein, the combined \"β-meso-core\" engineering of porphyrin produces excellent photothermal/photoacoustic agents that exhibit locally excited NIR bands with high molar extinction coefficients reaching 105 scale. The β-anthracene fusion of porphyrins via retro-Diels-Alder reactions extends the π-systems, generating red-shifted and intensified Q bands with narrow half-widths. The change of meso-substituents leads to distorted, non-aggregated molecules with improved solubility and fine-tunes the photophysical characteristics. The core coordination of copper ions promotes non-radioactive decay in the energy-releasing process and enhances photobleaching resistance. The biocompatible nanoparticles encapsulating the designed porphyrin exhibit a high photothermal conversion efficiency of 68% and promising photoacoustic responses, enabling effective photoacoustic imaging-guided photothermal therapy in vivo at a safe laser intensity (808 nm, 0.3 W cm- 2). This study provides a novel strategy in the molecular engineering of porphyrin for designing highly efficient photothermal agents.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500789"},"PeriodicalIF":10.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A Nanoplatform Targeting Cascade Pathways for Enhanced Triptolide Delivery in Acute Kidney Injury Therapy. 靶向级联通路的纳米平台增强雷公藤甲素在急性肾损伤治疗中的传递。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-12 DOI: 10.1002/adhm.202500595

Qianqian Guo, Xin Lu, Yanqi Zhang, Zhimin Huang, Shaobo Liu, Li Qiao, Xingjie Wu, Honglei Guo, Xiangchun Shen, Huijuan Mao

{"title":"A Nanoplatform Targeting Cascade Pathways for Enhanced Triptolide Delivery in Acute Kidney Injury Therapy.","authors":"Qianqian Guo, Xin Lu, Yanqi Zhang, Zhimin Huang, Shaobo Liu, Li Qiao, Xingjie Wu, Honglei Guo, Xiangchun Shen, Huijuan Mao","doi":"10.1002/adhm.202500595","DOIUrl":"https://doi.org/10.1002/adhm.202500595","url":null,"abstract":"Triptolide (TP), the main active compound in Tripterygium wilfordii Hook F, has anti-inflammatory and antioxidant properties, making it a potential treatment option for acute kidney injury (AKI). However, the application of TP faces challenges due to its poor water solubility, low renal accumulation, and potential tissue toxicity. To overcome these limitations, TL-N@TP is engineered as a cascade-targeted nanotherapeutic system integrating triphenylphosphonium (TPP)- and lysozyme (LZM)-functionalized PEG-PLGA copolymers for renal-specific TP delivery. The effectiveness of TL-N@TP is highlighted through a tripartite targeting mechanism, involving glomerular filtration, renal tubule specificity, and mitochondrial localization. The nanoplatform is able to target damaged kidneys and localize in the renal tubular cells in AKI mice induced by lipopolysaccharide. Upon uptake by injury HK-2 cells, the nanoplatform showed antioxidant, anti-inflammatory, and antiapoptotic effects. The nanoplatform in AKI mice effectively improved renal function by facilitating the restoration of mitochondrial structure and function, concomitant with reducing oxidative stress and inflammation. These findings establish TL-N@TP as a promising nanotherapeutic strategy for AKI management.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500595"},"PeriodicalIF":10.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A Wet-Adhesive Hydrogel Patch with Rapid-Adhesion, Anti-Swelling, and Pro-Healing Properties for Sutureless Repair of Dural Tear. 一种具有快速粘附、抗肿胀和促进愈合特性的湿粘水凝胶贴片用于无缝线修复硬脑膜撕裂。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-10 DOI: 10.1002/adhm.202500761

Hao Zhou, Yue Fan, Jiajun Huang, Hanwen Huang, He Li, Zhi Liang, Zhaopeng Cai, Youchen Tang, Peng Wang

{"title":"A Wet-Adhesive Hydrogel Patch with Rapid-Adhesion, Anti-Swelling, and Pro-Healing Properties for Sutureless Repair of Dural Tear.","authors":"Hao Zhou, Yue Fan, Jiajun Huang, Hanwen Huang, He Li, Zhi Liang, Zhaopeng Cai, Youchen Tang, Peng Wang","doi":"10.1002/adhm.202500761","DOIUrl":"https://doi.org/10.1002/adhm.202500761","url":null,"abstract":"Dural tears and subsequent cerebrospinal fluid leakage are common and intractable in spinal surgery. However, the existing clinical treatments are still unsatisfactory and the effective closure and repair of dural tears remain a huge challenge. Herein, a bilayer wet-adhesive hydrogel patch (denoted as BMTP) with rapid-adhesion, anti-swelling, and pro-healing properties is developed, which comprises a tough poly(vinyl alcohol) (PVA) dissipative layer and a functionalized poly(acrylic acid)-based wet-adhesive layer modified with methyl acrylate (MA) and tannic acid (TA). Owing to the hydrophobic effect of MA moieties and the strong intermolecular hydrogen bonding interaction facilitated by TA, BMTP has a unique low swelling property (24.2%) without compromising wet adhesion. Meanwhile, attributed to the high mechanical strength of the PVA dissipative layer and its mechanical interlocking with the wet-adhesive layer, BMTP exhibits durable sealing capacities with a burst pressure tolerance of 325 mm Hg. Moreover, the TA-mediated promotion of fibroblast proliferation enables BMTP to accelerate the healing of dura wounds. The rabbit dural tear model demonstrates that the BMTP can effectively seal and promote the healing of the damaged dura without postoperative adhesion within 3 weeks. Therefore, this work may offer a promising solution for the sutureless treatment of dural tears.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500761"},"PeriodicalIF":10.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Correction to "TP8, A Novel Chondroinductive Peptide, Significantly Promoted Neo-Cartilage Repair without Activating Bone Formation". 更正“TP8，一种新型的软骨诱导肽，在不激活骨形成的情况下显著促进新软骨修复”。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202502078

引用次数: 0

Selenide-Driven Reactive Oxygen Species Activation and Fe(II) Regeneration for Enhanced Nanocatalytic Antibacterial Therapeutics. 硒驱动的活性氧活化和铁（II）再生用于增强纳米催化抗菌治疗。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202501021

Chenyao Wu, Yanling You, Dehong Yu, Ya-Xuan Zhu, Han Lin, Jianlin Shi

{"title":"Selenide-Driven Reactive Oxygen Species Activation and Fe(II) Regeneration for Enhanced Nanocatalytic Antibacterial Therapeutics.","authors":"Chenyao Wu, Yanling You, Dehong Yu, Ya-Xuan Zhu, Han Lin, Jianlin Shi","doi":"10.1002/adhm.202501021","DOIUrl":"https://doi.org/10.1002/adhm.202501021","url":null,"abstract":"Fenton-based nanocatalytic therapy has attracted widespread attention for its high efficiency and safety. Nevertheless, Fe2+ regeneration, as the rate-limiting step of Fenton reaction, hinders the ROS-induced oxidative killing. Herein, a Fe2+ auto-regeneration strategy is exemplified by 2D FeSe2 nanosheets to break the rate limitation of Fenton reaction and subsequently enhances the antibacterial oxidative damage via dual ROS generation pathways. To be specific, the Se species accelerate the Fe3+ reduction to maintain high ·OH productivity of Fe2+-mediated Fenton reaction, which is accompanied by the production of H2Se in the presence of H+. The H2Se further converts O2 into O2 ·- and synergistically breaks the oxidative threshold of bacteria, leading to irreversible bacterial death with glutathione depletion, lipid peroxidation, and membrane destruction. In summary, the FeSe2-mediated Fe2+ auto-regeneration and ROS self-production pathways largely elevate its oxidative killing capability, providing a potential ROS enhancement strategy for broad-spectrum nonantibiotic bacterial disinfection.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501021"},"PeriodicalIF":10.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Bioengineering a Patient-Derived Vascularized Lung Tumor-on-Chip Model to Decipher Immunomodulation by the Endothelium. 用生物工程技术建立患者源性血管化肺肿瘤芯片模型，以破解内皮细胞的免疫调节。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202403446

Christine Lansche, Ségolène Ladaigue, Giacomo Gropplero, Nicolas Zimmermann, Martin Nurmik, Irina Veith, Manh-Louis Nguyen, Solenn Brosseau, Nicolas Poté, Pierre Mordant, Arnaud Roussel, Fathia Mami-Chouaib, Fatima Mechta-Grigoriou, Gérard Zalcman, Fabrice Soncin, Stéphanie Descroix, Maria Carla Parrini

{"title":"Bioengineering a Patient-Derived Vascularized Lung Tumor-on-Chip Model to Decipher Immunomodulation by the Endothelium.","authors":"Christine Lansche, Ségolène Ladaigue, Giacomo Gropplero, Nicolas Zimmermann, Martin Nurmik, Irina Veith, Manh-Louis Nguyen, Solenn Brosseau, Nicolas Poté, Pierre Mordant, Arnaud Roussel, Fathia Mami-Chouaib, Fatima Mechta-Grigoriou, Gérard Zalcman, Fabrice Soncin, Stéphanie Descroix, Maria Carla Parrini","doi":"10.1002/adhm.202403446","DOIUrl":"https://doi.org/10.1002/adhm.202403446","url":null,"abstract":"The endothelium compartment is a key player in tumor initiation and progression, but most existing tumor-on-chip models lack clinical relevance. Here, a 3D vascularized tumor-on-chip (vToC) model, generated with patient-derived microvascular endothelial cells (ECs) that are freshly isolated from surgical lung cancer samples, is presented. The microvessel molecular identity, morphology, and functionality are assessed by transcriptomic, immunofluorescence, TNF-α stimulation, and permeability assays. Lung cancer cells, cancer-associated fibroblasts (CAFs), and CD8+ tumor-infiltrating lymphocytes are embedded into the surrounding collagen matrix to partially recapitulate the lung tumor microenvironment (TME). The proof-of-concept of feasibility to generate personalized immunocompetent vToC composed of primary fully autologous cell types is provided. This vToC model is used to investigate the interplay between ECs and other TME cellular components by transcriptomic analysis. Using a rationally designed panel of endothelial genes, it is found that the presence of cancer cells and CAFs in the endothelial environment decreases expression by ECs of VCAM-1 leukocyte adhesion protein, a crucial regulator of immune infiltration, and of many immunomodulatory chemokines, recapitulating endothelial cell anergy. This in vitro model will be a valuable clinically-relevant tool to study the tumor-CAF-immune-endothelium interplay.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403446"},"PeriodicalIF":10.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Rod-shaped Polymerized Salicylic Acid Particles Modulate Neutrophil Transendothelial Migration in Acute Inflammation. 杆状聚合水杨酸颗粒在急性炎症中调节中性粒细胞跨内皮迁移。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202404955

M Valentina Guevara, Emma R Brannon, Daniel Kupor, Mariana R N Lima, Logan D Piegols, Michael L Felder, Kathryn E Uhrich, Omolola Eniola-Adefeso

{"title":"Rod-shaped Polymerized Salicylic Acid Particles Modulate Neutrophil Transendothelial Migration in Acute Inflammation.","authors":"M Valentina Guevara, Emma R Brannon, Daniel Kupor, Mariana R N Lima, Logan D Piegols, Michael L Felder, Kathryn E Uhrich, Omolola Eniola-Adefeso","doi":"10.1002/adhm.202404955","DOIUrl":"https://doi.org/10.1002/adhm.202404955","url":null,"abstract":"Neutrophilic inflammation is present in numerous high-mortality pathologies, including sepsis, deep vein thrombosis, and acute lung injury (ALI). Therefore, regulating neutrophil recruitment becomes an attractive therapeutic approach for neutrophil-mediated inflammation. Here, the impact of salicylic acid-based polymeric particles in regulating neutrophil recruitment in vivo and in vitro, particularly investigating the impact of neutrophil targeting via particle geometry-driven phagocytosis is explored. It is found that rod-shaped polymeric particles can improve neutrophil targeting in a murine ALI model, effectively preventing neutrophil infiltration into the mice's lungs compared to spherical particles of the same volume. It is demonstrated that the elongated nature of the polymeric carriers reduced neutrophils' transmigration ability across endothelial barriers in vivo and in vitro, contributing to their therapeutic effectiveness. These data represent initial work in developing non-spherical particle-mediated targeting of activated neutrophils for conditions affected by neutrophilic injury.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404955"},"PeriodicalIF":10.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Ultrasound-Activated Selenium Nanocarrier: Bactericidal Enhancement and Osseointegration Promotion for Implant-Associated Infections. 超声激活硒纳米载体：对种植体相关感染的杀菌增强和骨整合促进。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202500523

Zhiying Cao, Renhao Xu, Wenyi Zheng, Li Ma, Yanni He, Tianfeng Chen, Hongmei Liu

{"title":"Ultrasound-Activated Selenium Nanocarrier: Bactericidal Enhancement and Osseointegration Promotion for Implant-Associated Infections.","authors":"Zhiying Cao, Renhao Xu, Wenyi Zheng, Li Ma, Yanni He, Tianfeng Chen, Hongmei Liu","doi":"10.1002/adhm.202500523","DOIUrl":"https://doi.org/10.1002/adhm.202500523","url":null,"abstract":"Implant-associated infections (IAIs) are common and challenging complications of orthopedic surgery. The physical barrier formed by biofilms and the antioxidant defense system of bacteria shield them from attack by antimicrobial agents and immune cells, leading to irreversible bone loss and the failure of osseointegration. To address these challenges and enhance osseointegration in the presence of biofilm infections, a sequential therapy strategy is proposed using an ultrasound-activated nanocarrier, PLGA@H/Se, designed to disrupt bacterial defenses and subsequently enhancing osteogenic differentiation. As expected, PLGA@H/Se, when activated by ultrasound, induces a cavitation effect that disrupts the outer barrier of the biofilm, while promoting the deep delivery of encapsulated SeNPs and the antimicrobial peptide HHC-36. The SeNPs target the internal H₂S-based antioxidant defense in bacteria, thereby synergistically enhancing the bactericidal effect of HHC-36. Furthermore, the sustained release of SeNPs regulates selenoprotein expression, boosts antioxidant stress responses, and activates the Wnt/β-catenin pathway, which helps restore the osteogenic differentiation potential of BMSCs impaired by oxidative damage, both in vitro and in vivo. Collectively, this ultrasound-based sequential system facilitates functional osseointegration under pathological conditions, offering a practical and comprehensive strategy for treating IAIs.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500523"},"PeriodicalIF":10.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Magnesium Ions Induce Endothelial Cell Differentiation into Tip Cell and Enhance Vascularized Bone Regeneration. 镁离子诱导内皮细胞向尖端细胞分化并促进血管化骨再生。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202500274

Liang Wang, Xu Wang, Jicenyuan Wu, Junyu Chen, Zihan He, Jian Wang, Xin Zhang

{"title":"Magnesium Ions Induce Endothelial Cell Differentiation into Tip Cell and Enhance Vascularized Bone Regeneration.","authors":"Liang Wang, Xu Wang, Jicenyuan Wu, Junyu Chen, Zihan He, Jian Wang, Xin Zhang","doi":"10.1002/adhm.202500274","DOIUrl":"https://doi.org/10.1002/adhm.202500274","url":null,"abstract":"Vascularization has been considered an essential strategy for bone regeneration and can be promoted by magnesium ions (Mg2+). During angiogenesis, the differentiation of endothelial cells (ECs) into tip cell is a critical step since it controls the growth direction and pattern of new vascular sprouts. While several studies have noted the pro-angiogenic effects of Mg2+, however, their specific influence on tip cell formation is unclear. Therefore, this research seeks to examine the impact of Mg2+ on tip cells and elucidate the potential mechanisms involved. The results reveal that Mg2+ shows good compatibility and stimulates ECs to migrate and invade in vitro. Moreover, Mg2+ enhances EC spheroids sprouting and elevates the expression of genes linked to tip cells. The underlying mechanisms are that Mg2+ facilitates tip cell differentiation via the VEGFA-VEGFR2/Notch1 signaling pathway crosstalk and promotes migration and filopodia formation of tip cells and proliferation of stalk cells by inducing YAP nuclear translocation, culminating in the maturation of vascular networks. Furthermore, EC spheroids stimulated by Mg2+ load in hydrogel enhance vascularized bone regeneration in vivo. These findings enrich the understanding of how Mg2+ influence blood vessel formation and provide practical strategies for the development and design of magnesium-based biomaterials.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500274"},"PeriodicalIF":10.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Morphometric-Assisted Prediction of Developmental Toxicity Using Stem Cell-Based Embryo Models in Microwells. 利用微孔干细胞胚胎模型的形态计量学辅助预测发育毒性。

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-05-09 DOI: 10.1002/adhm.202404847

Vinidhra Shankar, Athanasia Zoi Pappa, Clemens van Blitterswijk, Erik Vrij, Stefan Giselbrecht

{"title":"Morphometric-Assisted Prediction of Developmental Toxicity Using Stem Cell-Based Embryo Models in Microwells.","authors":"Vinidhra Shankar, Athanasia Zoi Pappa, Clemens van Blitterswijk, Erik Vrij, Stefan Giselbrecht","doi":"10.1002/adhm.202404847","DOIUrl":"https://doi.org/10.1002/adhm.202404847","url":null,"abstract":"Congenital abnormalities cause ≈3% of fetal defects and premature deaths in Europe, often due to maternal exposure to toxicants. To mitigate the ethical and logistical challenges of animal studies, stem cell-based models are being exploredthat offer scalable readouts at various stages of embryogenesis. However, most current in vitro models are limited in complexity, throughput, automation compatibility or real-time spatio-temporal read-outs. In this study, a scalable, automated platform capable of imaging and quantifying morphological features such as shape, size, texture, and marker intensity is presented. Using a microwell screening platform, XEn/EpiCs, a peri-implantation stage embryo model that mimics eXtraembryonic Endoderm and Epiblast co-development, is robustly generated and used to screen a library of 38 reported compounds. Unlike conventional cytotoxicity assays, this approach also evaluates development-disrupting morphological changes, termed \"morphotoxicity\", thereby offering complementary insights that may improve the prediction of developmental toxicity across cell types. This pilot study shows thathigh doses of compoundslike retinoic acid, caffeine, ampyrone, and dexamethasone, significantly disrupt XEn/EpiC development, causing morphotoxic effects with or without affecting cell viability. Together, thisstudy highlights the importance of complementing cytotoxicity assessments with morphotoxicity read-outs, emphasizing its potential to enhance the evaluation of teratogenic risks in toxicity tests.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404847"},"PeriodicalIF":10.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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