Nicole J Blaine, Arianna Skirzynska, Allysia A Chin, Julie Audet, Molly S Shoichet
{"title":"The Role of Viscoelasticity in Heterogeneous Glioblastoma Stem Cell Invasion in Biomimetic 3-Dimensional Hydrogels.","authors":"Nicole J Blaine, Arianna Skirzynska, Allysia A Chin, Julie Audet, Molly S Shoichet","doi":"10.1002/adhm.71856","DOIUrl":"https://doi.org/10.1002/adhm.71856","url":null,"abstract":"<p><p>The role of viscoelasticity in cell invasion within the brain extracellular matrix (ECM) is not well understood in the context of glioblastoma (GBM). We designed biomimetic viscoelastic hyaluronan (HA)-based hydrogels to understand the effect of viscoelasticity on the invasion of heterogeneous glioblastoma stem cells (GSCs) categorized into subgroups based on molecular profile, as Reactive, Invasive, or Constructive. Hydrogel viscoelasticity was introduced to a hyaluronan-oxime (HAox) hydrogel to varying degrees through the incorporation of one of methyl cellulose, ECM-based proteins, tenascin C or collagen IV, or hydrazone chemistry. Each HAox-derived viscoelastic hydrogel exhibited significantly higher stress relaxation than HAox. We demonstrated that heterogeneous patient-derived GSC lines respond differently to viscoelasticity, with a strong correlation between greater invasion of Reactive GSCs in faster stress-relaxing matrices. This work highlights the importance of investigating the behavior of GSCs based on their heterogeneous molecular profiles and contributes to the understanding of the role of viscoelasticity in GSC invasion.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71856"},"PeriodicalIF":11.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178192","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}
{"title":"A Bioinspired Nanomedicine for Thermo-Catalytic Reprogramming of Obese Fat.","authors":"Ehsan Zolfaghari, Melisa Wei Ning Leoi, Lewen Zheng, Lynette Xiang Lin, Zheye Zhang, Aung Than, Melvin Khee Shing Leow, Asim Shabbir, Dong-Sheng Li, Peng Chen","doi":"10.1002/adhm.71832","DOIUrl":"https://doi.org/10.1002/adhm.71832","url":null,"abstract":"<p><p>Obesity is sustained by a self-reinforcing pathological microenvironment within white adipose tissue (WAT), characterized by a triad of hypoxia, oxidative and nitrosative stress, and chronic inflammation. However, current anti-obesity therapies target appetite regulation or nutrient absorption without directly correcting this local dysfunction. Here, we report a bioinspired organic single-atom nanozyme for localized thermocatalytic reprogramming of obese adipose tissue. The nanomedicine comprises atomically dispersed ruthenium catalytic centers embedded within a polydopamine framework (Ru@PDA), integrating enzyme-mimetic catalytic activity, antioxidant function, and NIR-II photothermal responsiveness into a single biocompatible platform. Delivered via an injectable crosslinked hyaluronic acid hydrogel for sustained retention in subcutaneous WAT, Ru@PDA exhibits superoxide dismutase- and catalase-like activities, efficiently scavenges reactive oxygen and nitrogen species, alleviates hypoxia, and generates mild hyperthermia to activate thermogenic signaling. These synergistic effects remodel the pathological adipose microenvironment, promoting adipocyte browning, lipolysis, adiponectin secretion, and anti-inflammatory macrophage polarization. In diet-induced obese mice, localized treatment reduced subcutaneous WAT (∼66%), distal visceral fat (∼68%), and body weight (∼16.9%), while largely restoring glycometabolic homeostasis and alleviating systemic oxidative stress and inflammation. Collectively, this work establishes thermo-catalytic reprogramming of the pathological adipose microenvironment as a promising therapeutic strategy for obesity and related metabolic disorders.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71832"},"PeriodicalIF":11.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178130","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}
Dan Li, Zuowei Xie, Ben Niu, Hong Yan, Hong Yi, Yifan Ma, Qing Yin, Ruijia Deng, Shuang Zhao, DongMing Wu, Ming Chen, Ying Xu, Kai Chang
{"title":"Receptor Dimerization-Engineering Hydrogel to On-Demand Regulate Cellular Behaviors.","authors":"Dan Li, Zuowei Xie, Ben Niu, Hong Yan, Hong Yi, Yifan Ma, Qing Yin, Ruijia Deng, Shuang Zhao, DongMing Wu, Ming Chen, Ying Xu, Kai Chang","doi":"10.1002/adhm.71852","DOIUrl":"https://doi.org/10.1002/adhm.71852","url":null,"abstract":"<p><p>Manipulation of cell-surface receptor dimerization plays a critical role in modulating cellular behaviors, yet the controllable regulation and dimerization efficiency of receptors remain challenging. Here, a dynamic bispecific aptamer within triglycerol monostearate (TGMS) nanoparticles hydrogel termed REMEDY (receptor dimerization-engineering directed hydrogel) was developed to modulate cellular behavior in an on-demand manner. The REMEDY was fabricated by dual rolling circle amplification to deliver bispecific receptor tyrosine kinase (RTK) aptamers, thereby effectively promoting cell receptor dimerization. The TGMS nanoparticles loaded with restriction endonuclease EcoR I controllably released bispecific RTK aptamers through EcoR I-triggered hydrogel disintegration in response to inflammation. The REMEDY successfully manipulated cell-surface MET receptor dimerization and activated MAPK/ERK and PI3K/AKT signaling pathways. RNA sequencing analysis further revealed that activated pathways upregulated the expression of Krt1, Vegfb, while downregulating Il1b, which were closely associated with target cells proliferation, migration, and phenotypic polarization. A murine wound model was subsequently constructed to validate the practical therapeutic efficacy. Results demonstrated that REMEDY significantly enhanced wound healing rates by 26.35% in acute wounds and 58.70% in chronic wounds. The REMEDY provides a paradigm for converting nanoscale molecular operation to the microscale behaviors regulation and paves the pathway for advancing precise cell therapy in regenerative medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71852"},"PeriodicalIF":11.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178179","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}
Neha Deshpande, Pauline Coquart, Bram Theuns, Susanne Cremery, Jaime Rodolfo V Garcia Iii, Julien Verplanken, Dennis Lambrechts, Dries Braeken, Liesbet Lagae, Johanna Bolander
{"title":"Single-Cell Resolution Mapping of Osteoarthritis-Associated Chondrocyte Dynamics Using a High-Density CMOS MEA Platform.","authors":"Neha Deshpande, Pauline Coquart, Bram Theuns, Susanne Cremery, Jaime Rodolfo V Garcia Iii, Julien Verplanken, Dennis Lambrechts, Dries Braeken, Liesbet Lagae, Johanna Bolander","doi":"10.1002/adhm.202504115","DOIUrl":"https://doi.org/10.1002/adhm.202504115","url":null,"abstract":"<p><p>Fibrosis is a major cause of chronic tissue dysfunction and contributes substantially to morbidity and mortality worldwide. Osteoarthritis (OA), affecting over 590 million people, is a prevalent fibrotic joint disease for which disease-modifying therapies remain lacking, partly because disease progression remains incompletely understood. As human-relevant in vitro models, including organ-on-chip and microphysiological systems, become increasingly important, non-invasive technologies capable of continuous cellular monitoring are urgently needed. Here, we implement high-density complementary metal-oxide-semiconductor (CMOS) multielectrode array (MEA)-based impedance profiling as a label-free platform for longitudinal assessment of OA-relevant chondrocyte remodeling. Human primary chondrocytes cultured on CMOS-MEA chips exhibited impedance increases that correlated with electrode occupancy and extracellular matrix (ECM) deposition. Spatial impedance mapping enabled visualization of injury-response dynamics, while oxidative stress induced progressive impedance decline accompanied by apoptosis, morphological remodeling, and chondrocyte dedifferentiation, evidenced by reduced collagen II and SOX9 expression and increased collagen I expression. In contrast, osteogenic de-differentiation produced increased impedance associated with ECM remodeling and matrix mineralization. Together, these findings support high-density CMOS-MEA impedance profiling as a non-invasive approach for monitoring cellular remodeling and provide a foundation for future integration of spatially resolved impedance sensing into advanced microphysiological systems for OA and other fibrotic diseases.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04115"},"PeriodicalIF":11.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178137","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}
{"title":"Immune‑Friendly Skin Interface Remodeling: Chiral Hydrogels for Diabetic Non-Healing Wound Therapy.","authors":"Hailu Yin, Yuetong Li, Baoding Qin, Yue Lei, Yanming Chen, Luoyuan Li","doi":"10.1002/adhm.71842","DOIUrl":"https://doi.org/10.1002/adhm.71842","url":null,"abstract":"<p><p>Diabetic non‑healing wounds pose a clinical challenge due to persistent inflammation, dysregulated immunity, and poor integration of dressings with the skin. Conventional hydrogel dressings have proven effective in providing physical barriers, moisture retention, and local drug delivery. Further optimization is still feasible for precise immune regulation and dynamic skin interfacial matching. In non-healing wound therapy, enantiomerically defined chiral hydrogels have emerged as a promising platform for targeted immune remodeling. By selectively steering macrophage polarization from pro-inflammatory M1 to pro-healing M2, they facilitate a smooth inflammatory-to-proliferative transition and accelerate wound closure. With rational network design, chiral hydrogels achieve favorable interfacial compatibility with the moist, dynamic wound environment, supporting cell adhesion, reducing friction induced microtrauma, sustaining bioactive signal delivery, and avoiding overt foreign body reactions. By integrating chiral topography, biomimetic mechanical properties, and moderate tissue adhesion, these hydrogels help establish an \"immune-friendly\" dermal interface. This review discusses structure-activity relationships linking chiral chemistry to immune cell behavior and outlines design principles for clinically translatable wound dressings. Collectively, chiral hydrogels that synergistically remodel immune microenvironment and ensure skin compatibility could redefine diabetic wound therapy, enabling a new paradigm of precision, immune‑instructive the wound management that transcends conventional dressing functions.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71842"},"PeriodicalIF":11.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178141","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}
Zhengjiang Xu, Yuan Zhang, Ben Wu, Junkang Chen, Qingge Fu, Lijing Fang, Jianghong Wu, Changshun Ruan, Haobo Pan, Yan Xia, Shuogui Xu, Guocheng Wang
{"title":"Coordination Reprogramming of Fe-Antibiotic Assemblies Enables Valence-Gated β-Lactam Reactivation.","authors":"Zhengjiang Xu, Yuan Zhang, Ben Wu, Junkang Chen, Qingge Fu, Lijing Fang, Jianghong Wu, Changshun Ruan, Haobo Pan, Yan Xia, Shuogui Xu, Guocheng Wang","doi":"10.1002/adhm.71836","DOIUrl":"https://doi.org/10.1002/adhm.71836","url":null,"abstract":"<p><p>Reactivating legacy antibiotics offers a practical route to combat drug-resistant infections, but requires delivery systems that coordinate bacterial engagement with pathogen-triggered drug release. Here, we report DFC, a deferoxamine (DFO)-reprogrammed Fe-carbenicillin (Car) coordination nanoassembly that restores the activity of the legacy β-lactam antibiotic Car against MRSA. DFC was fabricated via DFO-mediated competitive coordination, transforming homogeneous Fe-Car networks into heterogeneous Car-Fe-DFO structures. Computational modeling and spectroscopic analyses showed stronger Fe<sup>3+</sup>-DFO affinity than Fe<sup>3+</sup>-Car binding, DFO-induced redistribution of the Fe-centered ligand environment, and sharply weakened Fe-ligand stability after Fe<sup>3+</sup>-to-Fe<sup>2+</sup> conversion. This coordination reprogramming allowed DFC to remain assembled under nonreducing conditions but rapidly disassemble and release Car under reducing conditions or upon exposure to MRSA. DFC enhanced MRSA targeting, biofilm penetration, and intracellular Fe/Car-associated accumulation, while Fe-valence-triggered destabilization promoted Car release, disrupted iron homeostasis, amplified oxidative stress and lipid peroxidation, and damaged the bacterial envelope. Collectively, these synergistic effects re‑established β-lactam susceptibility, conferred robust antibacterial and anti‑biofilm efficacy, and markedly promoted pathogen clearance as well as tissue repair, as evidenced in both infected wound and osteomyelitis models. This study establishes competitive coordination reprogramming as a chemical strategy for coupling bacterial iron metabolism with antibiotic liberation and resistance reversal.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71836"},"PeriodicalIF":11.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178183","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}
{"title":"Cooperative Stem Cell Homing and Photothermal Protection Driven by an Injectable Hydrogel for Bone-Vascular Regeneration.","authors":"Shaowei Zheng, Yutai Li, Yuliang Huang, Yixin Xu, Jianping Zheng, Shoubin Huang, Yuanjian Ye, Rinkiko Suguro, Chunhan Sun, Hao Cheng, Honghua Cai, Guihua Liu","doi":"10.1002/adhm.71772","DOIUrl":"https://doi.org/10.1002/adhm.71772","url":null,"abstract":"<p><p>Bone defects caused by trauma or disease present significant clinical challenges, necessitating advanced biomaterials that simultaneously recruit stem cells and orchestrate a conducive microenvironment for repair. Here, we present an injectable hydrogel system designed to drive integrated bone-vascular regeneration through targeted stem cell homing and localized metabolic rescue. The composite hydrogel, crosslinked from gelatin and oxidized starch, integrates liposome-encapsulated stromal cell-derived factor-1 (SDF-1) and MXene-enabled GelMA microspheres. This minimally invasive system addresses two critical regenerative phases. First, liposomal SDF-1 undergoes controlled release to effectively recruit endogenous bone marrow mesenchymal stem cells (BMSCs). Concurrently, under near-infrared irradiation, the MXene-GelMA microspheres generate mild localized heat stress (40-42 °C). Crucially, this targeted photothermal therapy acts as a metabolic rescue mechanism; it upregulates heat shock protein 70 (HSP70) in BMSCs to mitigate apoptosis, stimulating endothelial cells to promote robust angiogenesis. In vitro, this cooperative environment significantly enhanced osteogenic differentiation and vascular network formation. In vivo application in a rat critical-sized calvarial defect model validated the hydrogel's therapeutic efficacy. At 8 weeks, the composite system increased the bone volume fraction (BV/TV) by 21.07% compared to a commercial bone repair material, accompanied by extensive neovascularization. This multifunctional hydrogel establishes a synchronized, translatable strategy for advanced tissue engineering.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71772"},"PeriodicalIF":11.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163473","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}
{"title":"Dual-Pathogen Defense: Engineering an ExPEC Ghost to Display Protective Epitopes of Streptococcus suis.","authors":"Jianan Liu, Xinming Pan, Zhen Zhang, Song Liang, Shiyu Zhang, Caiying Li, Simin Lv, Zhonghao Chen, Yinchu Zhu, Yinli Bao, Cuiqin Huang, Jinhu Huang, Jiale Ma","doi":"10.1002/adhm.71838","DOIUrl":"https://doi.org/10.1002/adhm.71838","url":null,"abstract":"<p><p>Streptococcus suis and extraintestinal pathogenic Escherichia coli (ExPEC) cause severe swine infections and major economic losses worldwide. Antimicrobial resistance (AMR) and polymicrobial interactions complicate disease control. Existing vaccine strategies are insufficient to provide broad cross-serotype protection against S. suis strains while simultaneously combating ExPEC infections. We developed a bivalent vaccine platform that integrates bacterial ghost (BG) technology with surface antigen display. By utilizing the porcine ExPEC strain PU-1 as a carrier, which could cause acute sepsis in mouse infection model. Using an Lpp'-OmpA surface display system, we constructed recombinant BGs derived from E. coli that express a multi-epitope antigen against S. suis (MEAS 1), while retaining native E. coli antigenic components as the immunogen against ExPEC. Administration of this vaccine induced robust cellular and humoral immune responses specific to both S. suis and E. coli. The vaccine demonstrated dual protection: 70%-90% survival against S. suis (serotypes 2/9) and 70% against ExPEC challenge in mouse model. Porcine trials demonstrated a significant reduction in bacteremia and provided effective protection against pathogenic challenges. This platform offers a potential solution for preventing infections caused by S. suis and ExPEC.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71838"},"PeriodicalIF":11.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163336","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}