Advanced Healthcare Materials最新文献_第10页

Monocyte-Mimetic Contrast Agent Enables Targeted and Sensitive Magnetic Resonance Imaging of Atherosclerotic Lesions. 单核细胞模拟造影剂使动脉粥样硬化病变的磁共振成像具有针对性和敏感性。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202502001

Joshua Rousseau, Ting-Yun Wang, Samantha McClendon, Dakota Ortega, Mark Orlando, Scott C Beeman, Benjamin B Bartelle, Kuei-Chun Wang

{"title":"Monocyte-Mimetic Contrast Agent Enables Targeted and Sensitive Magnetic Resonance Imaging of Atherosclerotic Lesions.","authors":"Joshua Rousseau, Ting-Yun Wang, Samantha McClendon, Dakota Ortega, Mark Orlando, Scott C Beeman, Benjamin B Bartelle, Kuei-Chun Wang","doi":"10.1002/adhm.202502001","DOIUrl":"https://doi.org/10.1002/adhm.202502001","url":null,"abstract":"Superparamagnetic iron oxide nanoparticles (SPION) are investigated as T2 contrast agents for magnetic resonance imaging (MRI) of atherosclerosis. However, their nonspecific biodistribution and low plaque-site bioavailability limit their translational potential. To address these challenges, monocyte membrane-cloaked polymeric nanoparticles encapsulating SPION (MoNP-SPION) to enhance plaque-specific accumulation is developed. Physicochemical characterization confirmed successful MoNP-SPION formulation, with a hydrodynamic size of ≈271 nm, SPION loading efficiency of 8.5%, and r2 relaxivity of 397.7 mM-1 s-1. In vitro assays and phantom imaging demonstrated that MoNP-SPION exhibited significantly enhanced targeting efficiency toward TNFα-activated endothelial cells while minimizing uptake by monocytes and macrophages compared to its constituents. T2*-weighted ex vivo MRI confirmed the preferential accumulation of MoNP-SPION in atheroprone regions while sparing lesion-free areas of the vasculature. In vivo MRI of atherosclerotic mice revealed that MoNP-SPION, but not the uncoated counterpart or free SPION, induced strong T2*-weighted signal reductions at the carotid bifurcations and aortic root, areas with significant plaque development, confirming its ability to enhance atherosclerosis imaging. Furthermore, toxicity assessments demonstrated the biocompatibility of MoNP-SPION. Together, the findings highlight MoNP-SPION as a promising biomimetic contrast agent for improving MRI-based diagnosis of atherosclerosis, with potential applications in monitoring plaque progression and treatment outcomes.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02001"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190420","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

Regulation of Retinal Microglia by Framework Nucleic Acid-Mediated Delivery of microRNA-124 Protects Retinal Ganglion Cells in Acute Glaucoma. 框架核酸介导的microRNA-124对急性青光眼视网膜神经节细胞的保护作用

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202500679

Cheng Zhang, Lemeng Feng, Weiming Zhu, Min He, Chao Wang, Ye He, Wulong Zhang, Jiayi Li, Haoze Song, Weitao Song

{"title":"Regulation of Retinal Microglia by Framework Nucleic Acid-Mediated Delivery of microRNA-124 Protects Retinal Ganglion Cells in Acute Glaucoma.","authors":"Cheng Zhang, Lemeng Feng, Weiming Zhu, Min He, Chao Wang, Ye He, Wulong Zhang, Jiayi Li, Haoze Song, Weitao Song","doi":"10.1002/adhm.202500679","DOIUrl":"https://doi.org/10.1002/adhm.202500679","url":null,"abstract":"Glaucoma is a leading cause of irreversible blindness, characterized by the progressive degeneration of retinal ganglion cells (RGCs) and optic nerve damage. Although current intraocular pressure (IOP)-lowering therapies exhibit varying degrees of efficacy in preventing RGC loss, neurodegeneration can persist even in cases where IOP remains within the normal range, underscoring the need for direct neuroprotective strategies. Emerging evidence suggests that neuroinflammation mediated by retinal microglia plays a pivotal role in the pathogenesis of glaucoma. Here, a nucleic acid-based nanotherapeutic platform is proposed that employs tetrahedral framework nucleic acids (tFNAs) conjugated with microRNA-124 (miR-124), referred to as Tmi, to achieve targeted immunomodulation. Compared with conventional delivery systems, this self-assembled nanostructure exhibits superior cellular penetration and nucleic acid protection capabilities. Mechanistic studies demonstrate that Tmi-mediated inhibition of the STAT3 pathway attenuates excessive microglial activation, reduces migration-associated inflammation, and suppresses pathological cell migration in an acute ocular hypertension model. This is an alternative treatment strategy beyond intraocular pressure control, offering greater possibilities for exploring therapies for acute high intraocular pressure glaucoma.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e00679"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190429","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

Biohybrid Bacteria as Living Nanofactories for Disrupting Diabetic Wound Pathological Cascade via Antimicrobial-Regenerative Coupling. 生物杂交细菌作为活纳米工厂，通过抗菌-再生耦合破坏糖尿病伤口病理级联。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202503107

Wendi Xuan, Yupei Hu, Sicong Li, Xiaozhen Zhou, Meng Chen, Chenyao Wu, Xiang Gao, Gaoyan Xu, Jine Zhao, Lili Xia, Wei Feng, Yu Chen

{"title":"Biohybrid Bacteria as Living Nanofactories for Disrupting Diabetic Wound Pathological Cascade via Antimicrobial-Regenerative Coupling.","authors":"Wendi Xuan, Yupei Hu, Sicong Li, Xiaozhen Zhou, Meng Chen, Chenyao Wu, Xiang Gao, Gaoyan Xu, Jine Zhao, Lili Xia, Wei Feng, Yu Chen","doi":"10.1002/adhm.202503107","DOIUrl":"https://doi.org/10.1002/adhm.202503107","url":null,"abstract":"Diabetic wound healing remains a formidable clinical challenge due to persistent biofilm formation, chronic inflammation, and excessive reactive oxygen species (ROS) accumulation. Current therapeutic approaches often lack synchronized antimicrobial-regenerative mechanisms and fail to provide sustained efficacy. Here, this work engineers a bioengineered living hydrogel system (BMB181@ALG) that leverages genetically modified Bacillus thuringiensis strain BMB181 as a melanin nanofactory, enabling in situ biosynthesis of multifunctional melanin nanoparticles (MNPs). Encapsulation within the hydrogel preserves bacterial metabolic activity, ensuring continuous MNPs production. These nanoparticles exhibit a dual-mode therapeutic action, including photothermal antibacterial activity under near-infrared irradiation for biofilm disruption and pathogen eradication, and ROS scavenging and antioxidant effects to modulate the inflammatory microenvironment. The sustained release of MNPs further promotes angiogenesis, enhances tissue regeneration, and dynamically regulates the diabetic wound microenvironment. Notably, the self-replenishing nature of this biohybrid system ensures long-term therapeutic efficacy, minimizing the need for frequent interventions. This study establishes a bacteria-driven therapeutic paradigm, demonstrating the translational potential of living microbial systems for next-generation precision wound management.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03107"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190384","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

Trans-Organ Early Intervention for Myocardial Infarction Based on Bone Marrow-Homing Biomimetic Nanomedicine. 基于骨髓归巢仿生纳米医学的心肌梗死跨器官早期干预。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202501619

Huaiyu Jiang, Haonan Zhang, Weichang Xie, Bei Qian, Shixing Huang, Junjie Zhang, Zhaoxi Qi, Qiang Long, Yiming Zhong, Lan Chang, Yecen Zhang, Zhao Qiang, Xiaofeng Ye

{"title":"Trans-Organ Early Intervention for Myocardial Infarction Based on Bone Marrow-Homing Biomimetic Nanomedicine.","authors":"Huaiyu Jiang, Haonan Zhang, Weichang Xie, Bei Qian, Shixing Huang, Junjie Zhang, Zhaoxi Qi, Qiang Long, Yiming Zhong, Lan Chang, Yecen Zhang, Zhao Qiang, Xiaofeng Ye","doi":"10.1002/adhm.202501619","DOIUrl":"https://doi.org/10.1002/adhm.202501619","url":null,"abstract":"Myocardial infarction (MI) elicits a robust inflammatory cascade, necessitating immunomodulatory strategies to attenuate neutrophil infiltration. Traditional invasive therapies, such as direct intramyocardial injections of anti-inflammatory factors or catheter-based local delivery of stem cells, are constrained by narrow therapeutic windows and can cause local tissue irritation and myocardial injury due to mechanical manipulation or puncture. Moreover, intravenous administration of anti-inflammatory agents often lacks specificity and targeted efficacy. Leveraging myeloma cell membrane-coated biomimetic nanomedicine encapsulating neutrophil chemotaxis inhibitors (MMNP@SB225002), a targeted therapeutic paradigm is engineered for the trans-organ early intervention modulation of the inflammatory cascade post-MI. By harnessing the bone marrow-homing (BMH) propensity, the therapeutic agent is efficiently trafficked to the bone marrow during the early post-MI response, markedly suppressing neutrophil mobilization. This strategy efficiently directs therapeutic agents to the bone marrow early after MI, significantly reducing neutrophil mobilization. By avoiding direct intervention at the infarction site and employing indirect modulation through peripheral immune organs, this approach sustainably mitigates myocardial fibrosis. The findings demonstrate that MMNP@SB225002 confers robust cardioprotection by alleviating post-MI inflammation. This innovative approach delineates a promising remote therapeutic strategy with substantial translational potential, underpinned by its enhanced safety profile.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01619"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190400","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

Ginsenoside CK Hybrid Exosome Composited Injectable Macroporous Hydrogel Scaffold for Cartilage Regeneration via Endogenous Bone Marrow Mesenchymal Stem Cells Recruitment and Fate Modulation. 人参皂苷CK杂交外泌体复合注射用大孔水凝胶支架内源性骨髓间充质干细胞募集及命运调控软骨再生。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202502550

Luoming Yang, Yajuan He, Dan Zeng, Caiyun Zhong, Yong Liu, Shihong Shen, Daidi Fan

{"title":"Ginsenoside CK Hybrid Exosome Composited Injectable Macroporous Hydrogel Scaffold for Cartilage Regeneration via Endogenous Bone Marrow Mesenchymal Stem Cells Recruitment and Fate Modulation.","authors":"Luoming Yang, Yajuan He, Dan Zeng, Caiyun Zhong, Yong Liu, Shihong Shen, Daidi Fan","doi":"10.1002/adhm.202502550","DOIUrl":"https://doi.org/10.1002/adhm.202502550","url":null,"abstract":"Osteoarthritis (OA)-induced cartilage repair critically relies on bone marrow mesenchymal stem cells (BMSCs). Three key challenges persist in OA therapy: efficient recruitment of BMSCs to lesions, sustained retention in defects, and inhibition of chondrocyte hypertrophy under inflammatory conditions. This study proposes a multidimensional repair strategy coordinating the entire process of \"endogenous BMSCs recruitment-retention/proliferation-differentiation-postdifferentiation fate-regulation.\" Accordingly, a ginsenoside CK (CK)-hybridized exosome (HyExo@CK) composite injectable microporous hydrogel scaffold (HyExo@CK/SiCH) is developed by integrating material strategies for multifunctional synergy. Detailly, the HyExo@CK enables endogenous BMSCs recruitment. The hydrogel scaffold, formed by in situ polysiloxane crosslinking of silane-modified recombinant collagen (functioning as surfactant-like foaming agent) and hyaluronic acid (serving as a high-viscosity rheological modifier and foam stabilizer), features interconnected macropores (171.40 ± 7.37 µm) that offer an optimal niche for BMSCs retention and proliferation. Cellular assays demonstrated HyExo@CK/SiCH significantly promoted BMSCs proliferation, migration, and chondrogenic differentiation. Computational modeling and OA-mimicking transcriptomic analysis revealed that CK competitively binds to the ligand-binding domain of SDF-1, effectively inhibiting the chondrocyte hypertrophy-associated SDF-1/CXCR4 signaling pathway to regulate BMSCs fate postdifferentiation. In rabbit OA cartilage defect models, HyExo@CK/SiCH achieved complete cartilage regeneration within 12 weeks postimplantation, demonstrating superior endogenous BMSCs recruitment and whole-cycle fate regulation capabilities.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02550"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190455","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

Hepatic-Targeted Liposomes-Ginger-Derived Exosomes Hybrid Nanocarrier for Synergistic Alleviation of Obesity-Induced Nonalcoholic Steatohepatitis. 肝靶向脂质体-姜源外泌体混合纳米载体协同减轻肥胖诱导的非酒精性脂肪性肝炎。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202503076

Yuhong Ma, Yukun Ma, Zhen Yuan, Jingxian Han, Dechun Huang, Hongliang Qian

{"title":"Hepatic-Targeted Liposomes-Ginger-Derived Exosomes Hybrid Nanocarrier for Synergistic Alleviation of Obesity-Induced Nonalcoholic Steatohepatitis.","authors":"Yuhong Ma, Yukun Ma, Zhen Yuan, Jingxian Han, Dechun Huang, Hongliang Qian","doi":"10.1002/adhm.202503076","DOIUrl":"https://doi.org/10.1002/adhm.202503076","url":null,"abstract":"Continued consumption of a high-calorie diet results in the excessive accumulation of lipids in visceral adipose tissue, thereby increasing the risk of nonalcoholic steatohepatitis (NASH). Herein, ginger-derived exosomes (G-Exos) loaded with berberine (G-Exos@B) to facilitate targeted delivery to the liver through the formation of GR-Exos@B via the coalescence of ursodeoxycholic acid (UDCA)-introduced liposomes (RAL) for effective NASH intervention are developed. The introduction of G-Exos significantly equipped GR-Exos@B to effectively overcome the multi-intestinal barrier, facilitating their exit from the cell in an intact form. Interestingly, the hepatic-targeting of RAL allowed GR-Exos to penetrate the liver more effectively than G-Exos, resulting in 2.39-fold greater accumulation in the liver. In vivo experiments revealed that dual ROS depletion by berberine and GR-Exos synergistically enhanced the therapeutic effect against inhibited oxidative stress and hepatocellular steatosis compared to GR-Exos. Additionally, the macrophage-targeting capability of G-Exos is leveraged to suppress the activation of hepatic NLRP3 inflammasome complexes, transitioning from an M1 pro-inflammatory to an M2 anti-inflammatory state, which helped diminish hepatic macrophage levels and subsequently reduce lipid accumulation. Meanwhile, GR-Exos@B improved insulin sensitivity primarily by strengthening the AMPK/AKT/IRS-1 signaling pathway and inhibiting GSK3-β function. Hence, GR-Exos@B shows promise as a potential strategy for alleviating obesity-induced NASH therapy.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03076"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190418","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

An Expandable Silk Fibroin/Montmorillonite Porous Scaffolds Based on Clinical Dual Hemostasis Concept and Its Application in Bone Regeneration of Tooth Extraction Sockets with Coagulation Disorders. 基于临床双重止血理念的可膨胀丝素/蒙脱土多孔支架及其在凝血障碍拔牙槽骨再生中的应用

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-30 DOI: 10.1002/adhm.202500930

Menglin Xiao, Liangyan Sun, Hao Fu, Wenhua Yang, Jinrong Yao, Zhengzhong Shao, Shengjie Ling, Bingjiao Zhao, Xin Chen

{"title":"An Expandable Silk Fibroin/Montmorillonite Porous Scaffolds Based on Clinical Dual Hemostasis Concept and Its Application in Bone Regeneration of Tooth Extraction Sockets with Coagulation Disorders.","authors":"Menglin Xiao, Liangyan Sun, Hao Fu, Wenhua Yang, Jinrong Yao, Zhengzhong Shao, Shengjie Ling, Bingjiao Zhao, Xin Chen","doi":"10.1002/adhm.202500930","DOIUrl":"https://doi.org/10.1002/adhm.202500930","url":null,"abstract":"With the global aging population and the rising incidence of cardiovascular diseases, the demand for long-term anticoagulant medication is increasing, leading to a higher risk of bleeding in medical fields such as oral surgery, particularly during tooth extractions. To address this clinical need, a convenient one-step method is developed to fabricate expandable silk fibroin/montmorillonite (SF/MMT) porous scaffolds by leveraging the procoagulant and osteogenic differentiation-promoting effects of montmorillonite (MMT), along with the biocompatibility of silk fibroin. The resulting SF/MMT porous scaffolds exhibit excellent shape recovery, with a volume expansion ratio of up to 400%. Furthermore, through the rapid blood absorption facilitated by the porous structure and the procoagulant effect of MMT, these scaffolds demonstrate superior hemostatic ability in both in vitro coagulation tests and in vivo rat tail amputation/liver laceration models. Finally, this expandable SF/MMT porous scaffolds used as hemostatic fillers showed significantly enhancement on bone regeneration in the tooth extraction socket of rat with coagulation disorders, outperforming commonly used gelatin sponges. In summary, this simple method for preparing expandable SF/MMT porous scaffolds addresses the challenge of managing post-extraction bleeding in patients on anticoagulant therapy and effectively promotes bone regeneration in extraction sockets, demonstrating considerable potential for application in stomatological clinic field.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e00930"},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190445","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

Atomic-Level Engineering of Synthetic Receptors for Enhanced Virus Detection and Removal (Adv. Healthcare Mater. 25/2025) 用于增强病毒检测和清除的合成受体的原子水平工程（Adv. Healthcare Mater. 25/2025）

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-29 DOI: 10.1002/adhm.70151

Eda Akin, Ekin Sehit, Nastasia Sanda Moldovean-Cioroianu, Sahana Tavaragondi, Sophia Slenczka, Roderich Süssmuth, Friedrich Jurk, Manuel van Gemmeren, Zeynep Altintas

引用次数: 0

Issue Information: Adv. Healthcare Mater. 25/2025 发布信息：Adv. Healthcare Mater. 25/2025

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-29 DOI: 10.1002/adhm.70192

引用次数: 0

Effect of 2D and 3D ECM and Biomechanical Cues on Human iPSC-Derived Liver Progenitor Cell Differentiation. 二维和三维ECM和生物力学线索对人ipsc来源的肝祖细胞分化的影响。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-29 DOI: 10.1002/adhm.202501370

Ishita Jain, Brock Grenci, Hyeon Ryoo, Yang Yuan, Salman R Khetani, Gregory H Underhill

{"title":"Effect of 2D and 3D ECM and Biomechanical Cues on Human iPSC-Derived Liver Progenitor Cell Differentiation.","authors":"Ishita Jain, Brock Grenci, Hyeon Ryoo, Yang Yuan, Salman R Khetani, Gregory H Underhill","doi":"10.1002/adhm.202501370","DOIUrl":"https://doi.org/10.1002/adhm.202501370","url":null,"abstract":"The differentiation of human liver tissue from induced pluripotent stem cells presents a powerful platform for drug screening and disease modeling. While 3D organoid systems effectively recapitulate tissue development, systematic investigation of microenvironmental parameters remains challenging. Here, complementary approaches are developed utilizing 2D cellular microarrays and 3D polyethylene glycol(PEG)-based microwells to examine human stem cell-derived hepatoblast differentiation. High-throughput microarray platform enables systematic evaluation of 60 distinct microenvironmental conditions, combining 15 ECM compositions with 4 growth factor treatments. Position-dependent expression of hepatocytic and cholangiocytic markers is observed including HNF4a, SOX9, and CK19, with differentiation patterns varying substantially across ECM and growth factor conditions. Based on these findings, specific ECM combinations are selected - Collagen 1, Fibronectin, and their combination - for integration into a modular 3D PEG hydrogel system. This 3D platform provides independent control over microtissue geometry and matrix composition, enabling investigation of spatial organization in hepatic differentiation. Through this integrated approach combining high-throughput screening and defined 3D culture, a framework is established for dissecting the microenvironmental regulation of human liver development.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01370"},"PeriodicalIF":9.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184225","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