Advanced Healthcare Materials最新文献_第6页

Metal-Polyphenol Network-Based Biomaterials for Infected Bone Defects: Microenvironment Regulation and Stage-Oriented Regenerative Strategies. 基于金属-多酚网络的感染性骨缺损生物材料：微环境调控和面向阶段的再生策略。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-12 DOI: 10.1002/adhm.71839

Yuanhong Li, Ziyi Xu, Yue Wang, Yuxuan Sun, Yuyou Qiu, Jiajia Qi, Yijun Xie

{"title":"Metal-Polyphenol Network-Based Biomaterials for Infected Bone Defects: Microenvironment Regulation and Stage-Oriented Regenerative Strategies.","authors":"Yuanhong Li, Ziyi Xu, Yue Wang, Yuxuan Sun, Yuyou Qiu, Jiajia Qi, Yijun Xie","doi":"10.1002/adhm.71839","DOIUrl":"https://doi.org/10.1002/adhm.71839","url":null,"abstract":"Infected bone defects are not simply bone defects complicated by bacterial infection; they are dynamic pathological niches in which biofilms, intracellular bacterial persistence, oxidative stress, dysregulated immunity, vascular failure, and pathological bone remodeling are mutually reinforcing. This coupling explains why bacterial killing alone rarely restores functional bone. Metal-polyphenol networks (MPNs), assembled through reversible coordination between metal ions and polyphenols, can translate these pathological stimuli into programmable therapy. Their tunable composition, interfacial adhesion, and pH/redox-responsive disassembly support a therapeutic transition from early infection control to redox-inflammatory regulation and vascularized bone regeneration. This review presents a disease-oriented framework connecting MPN chemistry and architecture with the evolving microenvironment of infected bone defects. Recent strategies for targeting planktonic and biofilm-associated bacteria, balancing reactive oxygen species generation and scavenging, reshaping osteoimmune signaling, protecting mitochondrial function, coupling angiogenesis with osteogenesis, and rebalancing bone remodeling are critically examined. Emphasis is placed on stage-oriented design, therapeutic trade-offs, and translational gaps. Priorities include eliminating hidden bacterial reservoirs, controlling ion dosing and long-term safety, evaluating functional vascularization and mechanical integration, and standardizing disease models. MPNs are thereby positioned as programmable platforms that coordinate infection resolution with durable bone regeneration.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71839"},"PeriodicalIF":11.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163601","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 Dual-Action Microneedle Patch Inhibiting Keratinocyte Ferroptosis and Scavenging Cell-Free DNA for Psoriasis Treatment. 抑制角化细胞铁下垂和清除游离DNA的双作用微针贴片治疗银屑病。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-12 DOI: 10.1002/adhm.71816

Jinmin Ye, Wenhao Li, Yatong Qin, Hui Liu, Hehe Xiong, Xiao Wang, Yujie Tian, Fantian Zeng, Weilin Chen, Changrong Shi, Jingxia Zhao, Wei Chen, Zijian Zhou

{"title":"A Dual-Action Microneedle Patch Inhibiting Keratinocyte Ferroptosis and Scavenging Cell-Free DNA for Psoriasis Treatment.","authors":"Jinmin Ye, Wenhao Li, Yatong Qin, Hui Liu, Hehe Xiong, Xiao Wang, Yujie Tian, Fantian Zeng, Weilin Chen, Changrong Shi, Jingxia Zhao, Wei Chen, Zijian Zhou","doi":"10.1002/adhm.71816","DOIUrl":"https://doi.org/10.1002/adhm.71816","url":null,"abstract":"Psoriasis is a chronic inflammatory skin disorder characterized by dysregulated epithelial-immune interactions. Emerging evidence implicates keratinocyte ferroptosis as a critical pathological mechanism, whereby oxidative epidermal damage and elevated levels of cell-free DNA (cfDNA) amplify immune dysregulation and sustain chronic psoriatic inflammation. Here, we developed a dual-action microneedle system (CAD), with needle tips composed of guanidine-functionalized chitosan and deferoxamine (DFO), designed to eliminate pro-inflammatory cfDNA while locally releasing DFO for iron chelation. In an imiquimod-induced psoriasis mouse model, CAD markedly alleviated psoriatic symptoms, reducing the psoriasis area and severity index score by approximately 50% compared with the model group and demonstrating superior therapeutic efficacy to clinically used calcipotriol. Further studies revealed that CAD depleted accumulated iron and inflammatory cfDNA in lesioned skin, alleviating oxidative stress and suppressing ferroptosis, inhibiting the inflammatory cascade, and maintaining immune homeostasis for effective psoriasis treatment. This study presents a dual-action microneedle therapy for psoriasis that alleviates psoriasis by modulating keratinocyte ferroptosis and scavenging cfDNA to restore inflammatory homeostasis, providing a promising foundation for the development of mechanism-guided combination therapies for psoriasis. Future work will further optimize the formulation for clinical translation and explore its therapeutic potential for other ferroptosis-related inflammatory skin disorders.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71816"},"PeriodicalIF":11.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163472","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

Hypoxia-Adaptive Confined Cascade Nanoplatform Unleashing ROS/RNS Storm and Metal Ions to Orchestrate Necroptosis, Ferroptosis, and cGAS-STING Immunity. 低氧适应性受限级联纳米平台释放ROS/RNS风暴和金属离子协调坏死性坏死、铁坏死和cgas刺痛免疫。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-12 DOI: 10.1002/adhm.71845

Zhi-Yuan Li, Ying-Ying Han, Qing-Hua Shen, Peng Wang, Long-Bo Yu, Cai-Ping Tan

{"title":"Hypoxia-Adaptive Confined Cascade Nanoplatform Unleashing ROS/RNS Storm and Metal Ions to Orchestrate Necroptosis, Ferroptosis, and cGAS-STING Immunity.","authors":"Zhi-Yuan Li, Ying-Ying Han, Qing-Hua Shen, Peng Wang, Long-Bo Yu, Cai-Ping Tan","doi":"10.1002/adhm.71845","DOIUrl":"https://doi.org/10.1002/adhm.71845","url":null,"abstract":"The hypoxic and immunosuppressive tumor microenvironment limits photodynamic therapy (PDT) and antitumor immunity. To address this, we construct a hypoxia-adaptive nanoplatform PG@Mn-ZIF8 by co-encapsulating a J-aggregating platinum photosensitizer Pt-3T and the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) within Mn2+/Zn2+ doped ZIF-8. This nanoplatform can decompose endogenous H2O2 to O2 via Pt aggregate-mediated catalase (CAT)-mimetic activity, alleviating hypoxia before light irradiation. Upon illumination, Pt-3T generates a robust Type I/II reactive oxygen species (ROS) storm, which triggers rapid NO release from GSNO, and further convert ROS and NO into highly cytotoxic peroxynitrite (ONOO•-), thereby amplifying an ROS/RNS storm within the confined MOF space. This co storm disrupts redox homeostasis to induce both necroptosis and ferroptosis alongside immunogenic cell death (ICD). Moreover, the released Mn2+ and Zn2+ upon MOF degradation synergistically potentiate the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway. Consequently, the spatiotemporal \"O2-ROS/RNS-metal ions\" cascade enables the nanoplatform to trigger multimodal cell death and ignite cGAS-STING-driven innate and adaptive immunity, eradicating solid tumors, establishing long-term immune memory, and reversing the \"cold\" tumor phenotype.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71845"},"PeriodicalIF":11.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163571","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

Unleashing the Potential of Autologous Platelet Concentrates in Bone Regeneration: A Focus on Their Synergy With Biomaterials. 释放自体血小板浓缩物在骨再生中的潜力：关注其与生物材料的协同作用。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-11 DOI: 10.1002/adhm.71821

Xin Chen, Dan Wu, Jing Yang, Bo Yang

{"title":"Unleashing the Potential of Autologous Platelet Concentrates in Bone Regeneration: A Focus on Their Synergy With Biomaterials.","authors":"Xin Chen, Dan Wu, Jing Yang, Bo Yang","doi":"10.1002/adhm.71821","DOIUrl":"https://doi.org/10.1002/adhm.71821","url":null,"abstract":"Bone defects present significant clinical challenges worldwide, as conventional treatments such as autografts and allografts are constrained by limited supply, immune risks and insufficient bioactivity. Derived from the patient's own venous blood via centrifugation, autologous platelet concentrates (APCs) offer an autologous, readily accessible source of growth factors and immune-related cues that can support osteogenesis, angiogenesis, and regenerative microenvironment remodeling. However, their standalone application is limited by intrinsic drawbacks, including mechanical weakness, rapid degradation, and transient growth factor release. To overcome these shortcomings, integrating APCs with various biomaterials has become a key strategy, providing structural support and modulating growth factor release. Across the literature, the evidence ranges from biological plausibility and preclinical support to limited early clinical feasibility, while proven clinical superiority remains uncertain for many combinations. This narrative review summarizes the classification, preparation, and osteogenic mechanisms of APCs, and discusses their combined application with diverse biomaterials across clinical scenarios based on evidence from in vitro to clinical studies. Furthermore, this review identifies current challenges and points out future directions, aiming to guide the rational design and clinical translation of more effective APC-biomaterial systems for bone regeneration.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71821"},"PeriodicalIF":11.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163583","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

Prostate Cancer Patient-Derived Organoids (PDOs) as Functional Avatars for Antisense Oligonucleotide (ASO)-Based Personalized Therapy. 前列腺癌患者衍生类器官（PDOs）作为基于反义寡核苷酸（ASO）的个性化治疗的功能化身。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-11 DOI: 10.1002/adhm.202505251

Thi Thom Tran, Thi Tu Uyen Phan, Michael Baboudjian, Quang Hieu Duong, Ines Sousa, Thi Thuy Le, Virginie Baylot, Sophie Giusiano, Laurent Daniel, Pauline Brige, Benjamin Guillet, Cyrille Bastide, Carmen Garrido, David Taïeb, Thi Khanh Le, Palma Rocchi

{"title":"Prostate Cancer Patient-Derived Organoids (PDOs) as Functional Avatars for Antisense Oligonucleotide (ASO)-Based Personalized Therapy.","authors":"Thi Thom Tran, Thi Tu Uyen Phan, Michael Baboudjian, Quang Hieu Duong, Ines Sousa, Thi Thuy Le, Virginie Baylot, Sophie Giusiano, Laurent Daniel, Pauline Brige, Benjamin Guillet, Cyrille Bastide, Carmen Garrido, David Taïeb, Thi Khanh Le, Palma Rocchi","doi":"10.1002/adhm.202505251","DOIUrl":"https://doi.org/10.1002/adhm.202505251","url":null,"abstract":"Patient-derived tumor organoids (PDOs) closely preserve the cellular heterogeneity, histopathology, and molecular features of the original tumors, making them powerful preclinical models. Antisense oligonucleotides (ASOs) are an emerging class of precision medicines that modulate gene expression at the RNA level with high target specificity, yet their application in organoid systems remains underexplored. Here, we adapted previously described protocols to establish a biobank of prostate cancer (PC) PDOs, achieving a high initial growth success rate (>90%). Histological and molecular analyses confirmed the preservation of key tumor features. Using these models, we assessed several ASOs, with particular emphasis on OGX-427 (Apatorsen), an ASO targeting heat shock protein 27 (HSP27) that has been evaluated in phase I/II clinical trials. While OGX-427 effectively suppressed HSP27 expression and inhibited cell growth in 2D cultures, its efficacy was markedly limited in 3D organoids, likely due to extracellular matrix and structural barriers. Removing Matrigel and applying single-cell transfection overcame these barriers, achieving efficient ASO uptake, significant target protein downregulation, and robust, dose-dependent inhibition of organoid growth. These findings underscore the utility of PDOs for evaluating ASO-based therapies and their potential to accelerate precision oncology strategies for PC and other malignancies.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05251"},"PeriodicalIF":11.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163464","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

Zonation Hallmarks in Human PSC-Derived Hepatic Organoids Integrated into an Immune-Compatible Organ-on-Chip for Liver Injury Modeling. 将人类psc衍生的肝类器官整合到免疫兼容器官芯片中用于肝损伤建模的分区特征。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-11 DOI: 10.1002/adhm.71834

Aleksandra Aizenshtadt, Andrea Dalmao-Fernández, Justyna Stokowiec, Kristina Sæterdal Kømurcu, Tharvesh M Liyakat Ali, Tonje Monica Erlandsson, Frøydis Sved Skottvoll, Mathias Busek, Alexey Golovin, Inger Øynebråten, Katharina Ferencevic, Brian K Chung, Jonas Øgaard, Alexandre Corthay, Hanne Røberg-Larsen, Espen Melum, Steven Ray Wilson, Stefan Krauss

{"title":"Zonation Hallmarks in Human PSC-Derived Hepatic Organoids Integrated into an Immune-Compatible Organ-on-Chip for Liver Injury Modeling.","authors":"Aleksandra Aizenshtadt, Andrea Dalmao-Fernández, Justyna Stokowiec, Kristina Sæterdal Kømurcu, Tharvesh M Liyakat Ali, Tonje Monica Erlandsson, Frøydis Sved Skottvoll, Mathias Busek, Alexey Golovin, Inger Øynebråten, Katharina Ferencevic, Brian K Chung, Jonas Øgaard, Alexandre Corthay, Hanne Røberg-Larsen, Espen Melum, Steven Ray Wilson, Stefan Krauss","doi":"10.1002/adhm.71834","DOIUrl":"https://doi.org/10.1002/adhm.71834","url":null,"abstract":"Liver metabolic zonation enables hepatocytes to carry out diverse, spatially organized functions essential for liver homeostasis and metabolism. However, in vitro recapitulation of zone-specific diversity, particularly in human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs), remains challenging, as these cells typically exhibit an immature phenotype. Here, we report a scalable differentiation protocol for generating 3D organoids from PSCs with defined zone 1 (z1-HLCs) or zone 3 (z3-HLCs) identities. When benchmarked against primary human hepatocytes (PHHs), these HLCs exhibit zone-specific enhanced postnatal metabolic functions. z1-HLCs reveal high albumin and urea production, whereas z3-HLCs show elevated glutamine secretion and cytochrome P450 (CYP) enzyme activity, including CYP3A4, CYP1A2, and CYP2C9. Hallmarks of functional zonation were further confirmed via proteomics, transcriptomics, metabolic assays, and oxygen consumption. z3-HLCs show increased sensitivity to acetaminophen-induced cytotoxicity and distinct immune interactions with primary monocytes. Collectively, the zonated liver organoids provide a promising platform for studying zone-specific liver metabolism, drug metabolism, toxicology, and liver disease, including liver injury.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71834"},"PeriodicalIF":11.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163425","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

Mass Spectrometry Imaging Reveals Biodistribution and Biotransformation of Black Phosphorus. 质谱成像揭示黑磷的生物分布和生物转化。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-11 DOI: 10.1002/adhm.71824

Xiu Huang, Jie Gao, Xinwei Liu, Jinhong Gao, Xiaolei Liu, Hua Qin, Guangbo Qu, Qian Liu, Guibin Jiang

{"title":"Mass Spectrometry Imaging Reveals Biodistribution and Biotransformation of Black Phosphorus.","authors":"Xiu Huang, Jie Gao, Xinwei Liu, Jinhong Gao, Xiaolei Liu, Hua Qin, Guangbo Qu, Qian Liu, Guibin Jiang","doi":"10.1002/adhm.71824","DOIUrl":"https://doi.org/10.1002/adhm.71824","url":null,"abstract":"Black phosphorus (BP) holds significant potential in biomedicine, biosensing, and phototherapy; however, its instability and the poor understanding of its in vivo fate have limited its applications. Here, we developed an integrated label-free mass spectrometry imaging (MSI) platform to investigate BP's in vivo distribution, transformation, clearance, and metabolism in tumor-bearing mice. We detected BPs and related nitrogen/oxygen-containing phosphorus (P) clusters in six organs and tumor tissues, revealing distinctive tissue distributions. BP and its degradation products primarily accumulated in the liver and spleen, with the liver showing a radial distribution pattern around hepatic lobules. Notably, BP and related clusters can cross the blood-brain barrier into brain parenchyma. We further establish the in vivo transformation and metabolic pathways of BPs. Cellular experiments confirmed that nitric oxide synthase (NOS)-mediated nitric oxide (NO) generation drives BP nitridation during its transformation and metabolism under physiological conditions. This work not only provides vital information for biomedical applications of BP, but also establishes a platform for understanding in vivo translocation and transformation of nanomaterials, aiding their biosafety and health impact assessments.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71824"},"PeriodicalIF":11.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163321","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

Photo-Controlled Treatment for Psoriasis-Like Skin Lesions by UVB-Photoactivated Hydrogen Sulfide Donors and Pterostilbene. uvb光激活硫化氢供体和紫檀芪光控治疗牛皮癣样皮肤病变。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-11 DOI: 10.1002/adhm.71835

Jia Lin, Yingting Wu, Chen Li, Haoyang Li, Fei Wang, Jieyu Liu, Liqing Yu, Zhongjian Chen, Xiaoyan Cui, Ting Wang

{"title":"Photo-Controlled Treatment for Psoriasis-Like Skin Lesions by UVB-Photoactivated Hydrogen Sulfide Donors and Pterostilbene.","authors":"Jia Lin, Yingting Wu, Chen Li, Haoyang Li, Fei Wang, Jieyu Liu, Liqing Yu, Zhongjian Chen, Xiaoyan Cui, Ting Wang","doi":"10.1002/adhm.71835","DOIUrl":"https://doi.org/10.1002/adhm.71835","url":null,"abstract":"Smart and efficient drug delivery is always desirable, especially for chronic diseases, such as psoriasis. We developed an ultraviolet B (UVB) light-triggered scaffold, 1,4,2-dioxazol-5-thione (DOT), for the controlled release of hydrogen sulfide (H2S), a pivotal endogenous gaseous signaling molecule with promise for anti-inflammatory and antioxidant therapies. In the DOT scaffold, the kinetics for H2S release are efficiently tuned by fine-adjusting the electronic properties. Upon photoirradiation, DOT releases carbonyl sulfide (COS), which is rapidly converted to H2S by carbonic anhydrase (CA). Furthermore, the DOT platform is conjugated to the active pharmaceutical ingredient pterostilbene (PTE) to afford a hybrid prodrug, PTE-DOT. Under UVB irradiation at 308 nm, a standard wavelength for psoriasis phototherapy, PTE-DOT simultaneously released H2S and PTE, thereby exerting combined anti-inflammatory and antioxidant effects in vivo. In the psoriasis mouse model, PTE-DOT effectively reduced epidermal thickening and hyperkeratosis, suppressed the production of key psoriatic inflammatory cytokines, and inhibited the differentiation of Th17 cells in the spleen. Thus, the photo-controlled prodrug strategy provides a platform for designing smart drug delivery systems to ameliorate psoriasis-like skin inflammation.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71835"},"PeriodicalIF":11.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163308","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

Engineered Microvascular Model of the Blood–Brain–Tumor Barrier Reveals Endothelial Remodeling in Diffuse Midline Glioma 血流-脑-瘤屏障工程微血管模型揭示弥漫性中线胶质瘤内皮重塑。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-07-28 DOI: 10.1002/adhm.71474

Kimberly R. Bennett, Yann S. Vanrobaeys, Tessy Teboh, Zakiya Smith, Anderson Scott, Cynthia Hajal, Paula T. Hammond, Joelle P. Straehla

{"title":"Engineered Microvascular Model of the Blood–Brain–Tumor Barrier Reveals Endothelial Remodeling in Diffuse Midline Glioma","authors":"Kimberly R. Bennett, Yann S. Vanrobaeys, Tessy Teboh, Zakiya Smith, Anderson Scott, Cynthia Hajal, Paula T. Hammond, Joelle P. Straehla","doi":"10.1002/adhm.71474","DOIUrl":"10.1002/adhm.71474","url":null,"abstract":"Diffuse midline glioma (DMG) is a highly aggressive pediatric brain tumor that is difficult to treat because the blood–brain–tumor barrier (BBTB) prevents most drugs from reaching the tumor. A major obstacle for understanding this tumor-vascular niche is the lack of a perfusable vascular model of DMG. To address this, we have established an in vitro model of the DMG-BBTB, comprised of patient-derived DMG tumor cells and primary human brain microvascular endothelial cells, astrocytes, and vascular pericytes, embedded in a fibrin matrix within a microfluidic chip. We report the development and characterization of self-assembled microvascular networks, with consistent vasculature development across a range of tumor cell densities. Perfusion studies showed no significant alterations in vascular permeability when tumor cells were present. To elucidate transcriptomic changes, we employed scRNAseq on devices containing blood–brain barrier (BBB), DMG-BBTB, or tumor necrosis factor alpha (TNFα)-stimulated control. We observed significant differential gene expression between BBB and DMG-BBTB, distinct from inflammatory signatures seen with TNFα perturbation. Our analysis indicated that DMG cells adopted a mesenchymal-like phenotype, with further in silico studies predicting significant receptor-ligand crosstalk between these cells and endothelium. In summary, we developed a high-fidelity DMG-BBTB model that recapitulates transcriptomic features of patient DMG microvasculature and features perfusable vasculature.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.71474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HydroMEA: A 3D Hydrogel-Based Microfluidic Device to Study Electrophysiology for Myelinated Nerve-on-Chip 基于三维水凝胶的微流体装置研究芯片上髓鞘神经的电生理。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-08-26 DOI: 10.1002/adhm.71655

Blandine F. Clément, Cédric Pfister, Timothy Kurer, Nicole Baalbaki, Max Paxtian, Jeeho Sim, Céline Labouesse, Dhanajay V. Deshmukh, Julian Hengsteler, Julia Lehmann, Lorenza G. Paganella, Tobias Ruff, Vilius Dranseika, Sean Weaver, Lukas Sommer, Mark W. Tibbitt, János Vörös, Christina M. Tringides

{"title":"HydroMEA: A 3D Hydrogel-Based Microfluidic Device to Study Electrophysiology for Myelinated Nerve-on-Chip","authors":"Blandine F. Clément, Cédric Pfister, Timothy Kurer, Nicole Baalbaki, Max Paxtian, Jeeho Sim, Céline Labouesse, Dhanajay V. Deshmukh, Julian Hengsteler, Julia Lehmann, Lorenza G. Paganella, Tobias Ruff, Vilius Dranseika, Sean Weaver, Lukas Sommer, Mark W. Tibbitt, János Vörös, Christina M. Tringides","doi":"10.1002/adhm.71655","DOIUrl":"10.1002/adhm.71655","url":null,"abstract":"<div>\u0000 \u0000 Engineered in vitro platforms are powerful systems to study information flow in the nervous system. While existing polydimethylsiloxane (PDMS)-based microfluidic platforms offer precise architectures, the cultured neurons grow on two-dimensional (2D) planar multielectrode arrays (MEA). To mimic the native microenvironment, where neurons grow in three-dimensional (3D) extracellular matrices (ECM), 3D hydrogels can be designed to encapsulate cells and enable physiologically mimicked behaviors. Here, we describe ‘hydroMEA,’ a 3D platform fabricated by placing PDMS microstructures on a high-density MEA and filled with a desired hydrogel, to offer controlled topologies, physiologically relevant microenvironments, and real-time electrophysiological measurements. First, we developed a gelatin methacryloyl (GelMA) hydrogel with incorporated ECM components and tuned the mechanical properties to match those of nerve tissue. The hydrogel was able to support: (1) the growth of iPSC-derived sensory neurons (hSNs) for >100 days; (2) co-cultures of hSN with human embryonic stem cell-derived Schwann cells (hSCs), to enable reliable 3D myelination. Next, hydroMEA were prepared for topologically defined 3D growth and myelination in designated compartments. Finally, electrophysiological evaluation of hSN-hSCs co-cultures revealed increased conduction speeds indicating functional myelin. This platform is a promising tool to study cell-cell interactions and to functionally evaluate the effect of pharmacological compounds in a more translational manner.\u0000 </div>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823747","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