BiomaterialsPub Date : 2026-06-01Epub Date: 2026-01-10DOI: 10.1016/j.biomaterials.2026.123996
Daniela Isaacs-Bernal , Brenda Coles , Lia Huo , Noor E. Bahsoun , Siming Wang , Derek van der Kooy , Molly S. Shoichet
{"title":"Tuning hydrogel affinity to control the release of antibodies","authors":"Daniela Isaacs-Bernal , Brenda Coles , Lia Huo , Noor E. Bahsoun , Siming Wang , Derek van der Kooy , Molly S. Shoichet","doi":"10.1016/j.biomaterials.2026.123996","DOIUrl":"10.1016/j.biomaterials.2026.123996","url":null,"abstract":"<div><div>The discovery of specific affinity interactions has paved the way for the development of functional hydrogel systems that enable tunable protein release via non-covalent interactions. This study explores, for the first time, the controlled release of antibody-based therapeutics via affinity interactions with specific fragment crystallizable domain peptide ligands (FcLs) immobilized within a hydrogel system. As a proof of concept, a dual-antibody delivery strategy was designed to stimulate retinal stem cells in the adult mammalian eye, co-releasing Fc-Noggin (targeting bone morphogenic proteins) and anti-sFRP2 (targeting secreted frizzle related protein-2). An FcL capable of binding to both Fc-Noggin and anti-sFRP2 with comparable affinity (10<sup>−8</sup> M) was functionalized onto a hyaluronan-based hydrogel that leverages oxime chemistry for network crosslinking and inverse electron demand Diels-Alder for FcL conjugation. In vitro, FcL1-functionalized hydrogels exhibited affinity-mediated retention of these therapeutics, reducing burst release and preserving protein stability. In vivo, a single intravitreal injection of the hydrogel formulation activated retinal stem cells, in adult CD1 mice, over four days to a similar extent as 3 repeated bolus injections of Fc-Noggin and anti-sFRP2 in saline, demonstrating the advantage of hydrogel-based delivery over bolus administration. This platform technology holds significant potential for broader application to other antibody-based therapies and offers a promising approach for local delivery in the eye.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123996"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-22DOI: 10.1016/j.biomaterials.2025.123927
Qingzhou Kong , Yinuo Zhao , Haifan Gong , Luoyao Kang , Jialu Fu , Lixiang Li , Boyao Wan , Peizhu Wang , Xiaojuan Li , Yue Wang , Jinghui Zhang , Yanbo Yu , Xiaoyun Yang , Xiuli Zuo , Haina Wang , Yanqing Li
{"title":"AI agent-based discovery of D-enantiomeric antimicrobial peptides against multidrug-resistant bacterial infection","authors":"Qingzhou Kong , Yinuo Zhao , Haifan Gong , Luoyao Kang , Jialu Fu , Lixiang Li , Boyao Wan , Peizhu Wang , Xiaojuan Li , Yue Wang , Jinghui Zhang , Yanbo Yu , Xiaoyun Yang , Xiuli Zuo , Haina Wang , Yanqing Li","doi":"10.1016/j.biomaterials.2025.123927","DOIUrl":"10.1016/j.biomaterials.2025.123927","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) offer a route to counter resistant pathogens but are often hampered by proteolysis, whereas D-peptides resist proteases yet remain underexplored due to data scarcity and design challenges. Here, we present PeptiD-Agent, a purely agent based framework that predicts D-peptide antimicrobial activity with extremely limited data, enabling rapid discovery of potent candidates. Using this approach, we identified DA2, a D-enantiometric AMP lead with broad-spectrum activity against drug-resistant bacteria and minimal hemolytic toxicity. DA2 showed high stability under physiological conditions, including resistance to enzymatic degradation and serum. Mechanistic studies indicate that DA2 exerts bactericidal effects by disrupting the integrity of the bacterial membrane in concert with multiple synergistic mechanisms. In murine models of skin wounds and intraperitoneal infection, DA2 conferred significant protection against drug-resistant pathogens and, when delivered via hydrogel, accelerated wound healing. These findings establish a computational route to potent, stable D-peptide antimicrobials and provide a general strategy for AMP design in data-scarce settings.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123927"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-19DOI: 10.1016/j.biomaterials.2025.123932
Austin Lai , Ying Zhou , Chanly Chheang , Azadeh Mirabedini , Yasmin Mirzaalikhan , Jonathan Noonan , Anna Watson , Nalin H. Dayawansa , Wenzhi Huang , Manijeh Khanmohammadi , Shadi Houshyar , Agus Salim , Karlheinz Peter , Sara Baratchi
{"title":"Decoding vascular aging: Substrate stiffness and shear stress orchestrate endothelial inflammation and remodelling via mechanosensitive pathways","authors":"Austin Lai , Ying Zhou , Chanly Chheang , Azadeh Mirabedini , Yasmin Mirzaalikhan , Jonathan Noonan , Anna Watson , Nalin H. Dayawansa , Wenzhi Huang , Manijeh Khanmohammadi , Shadi Houshyar , Agus Salim , Karlheinz Peter , Sara Baratchi","doi":"10.1016/j.biomaterials.2025.123932","DOIUrl":"10.1016/j.biomaterials.2025.123932","url":null,"abstract":"<div><div>Vascular ageing is a major contributor to cardiovascular disease and is closely linked to vascular stiffness. Stiffening of the vascular wall disrupts endothelial homeostasis and promotes chronic inflammation, yet the underlying mechanisms remain poorly understood due to technological limitations. Here, we used a previously developed <em>in vitro</em> microfluidic model to investigate how biomechanical forces, specifically substrate stiffness and shear stress, interact to regulate endothelial cell behaviour. Using RNA sequencing and functional assays, we found that endothelial cells exposed to both physiological and high levels of shear stress were more sensitive to increases in substrate stiffness. Under these conditions, the cells exhibited a greater number of differentially expressed genes and enhanced activation of inflammatory signalling pathways, suggesting that mechanical stiffening promotes endothelial inflammation and contributes to vascular ageing.</div><div>We identified enriched pathways involved in inflammatory signalling and extracellular matrix (ECM) remodelling in response to substrate stiffness. Endothelial cells exposed to high shear stress and increased stiffness showed up-regulation of genes such as <em>ICAM1</em>, <em>VCAM1</em>, <em>LAMB3</em>, and <em>MMP28</em>, which are known to mediate leukocyte adhesion and ECM remodelling. Importantly, benchmarking our engineered <em>in vitro</em> microfluidic model using human aortic tissue confirmed concordant molecular and histological changes between stiff (aged) and soft (healthy) aortas. Ultimately, this validated microfluidic platform provides proof of concept that biomechanical forces characteristic of vascular ageing drive endothelial inflammation and vascular remodelling, offering new mechanistic insight and a powerful experimental framework to advance therapeutic strategies targeting vascular stiffness and age-related vascular disease.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123932"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-18DOI: 10.1016/j.biomaterials.2025.123933
Lili Huang , Pengfei Yang , Chenli Zhang , Ling Tan , Lingshan Zhao , Liling Yang , Ling Zhang , Zheng Zhang , Jun Deng , Xiaohui Liao
{"title":"Sequential-targeting nanomedicine protects against acute kidney injury by modulating calcium influx and scavenging reactive oxygen species","authors":"Lili Huang , Pengfei Yang , Chenli Zhang , Ling Tan , Lingshan Zhao , Liling Yang , Ling Zhang , Zheng Zhang , Jun Deng , Xiaohui Liao","doi":"10.1016/j.biomaterials.2025.123933","DOIUrl":"10.1016/j.biomaterials.2025.123933","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a global health challenge responsible for approximately 1.7 million deaths each year. Current treatment options, such as renal replacement therapy and supportive care, are limited to systemic support and fail to promote repair of dysfunctional renal tubular epithelial cells (RTECs). In this study, we developed a macrophage membrane-coated sequential-targeting nanodrug, MA-5@MΦ-LSALT, which leverages the LSALT targeting peptide to selectively deliver the nanodrug to injured RTECs. Upon reaching the damaged RTECs, the released mitochonic acid-5 (MA-5) further localizes to mitochondria. In both cisplatin-induced and ischemia–reperfusion AKI models, MA-5@MΦ-LSALT inhibited calcium influx and reduced reactive oxygen species levels. Collectively, this work introduces an innovative sequential-targeting strategy from kidneys to RTECs to mitochondria that effectively addresses the challenge of targeted repair in AKI and highlights a promising therapeutic avenue for clinical translation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123933"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-31DOI: 10.1016/j.biomaterials.2025.123970
Rui Xue , Fengyu Wang , Beibei Zhang , Jin Wu , Ningnannan Zhang , Chunyang Sun
{"title":"Carrier-free nanoassembly with dual antioxidant and anti-inflammatory activities camouflaged by melanoma cell membrane for tau-targeted therapy of Alzheimer's disease","authors":"Rui Xue , Fengyu Wang , Beibei Zhang , Jin Wu , Ningnannan Zhang , Chunyang Sun","doi":"10.1016/j.biomaterials.2025.123970","DOIUrl":"10.1016/j.biomaterials.2025.123970","url":null,"abstract":"<div><div>Targeting phosphorylated tau (p-tau) across the blood–brain barrier (BBB) represents a critical prerequisite for attenuating tau pathology and disease progression in Alzheimer's disease (AD) by alleviating oxidative stress and neuroinflammation. To address this challenge, we developed a novel carrier-free selenium-based nanoassembly stabilized by hydroxyl-rich fingolimod (FTY720), a sphingosine analogue. Following camouflaging with melanoma cell membranes and further functionalizing with T807, the resulting nanocomposite (FSMT) demonstrated robust capacity for BBB crossing and target p-tau both <em>in vitro</em> and <em>in vivo</em>. Additionally, FTY720 and nano-selenium exert remarkable antioxidant and anti-inflammatory effects by modulating the GSK-3β and NF-κB signaling pathways, respectively, thereby attenuating tau hyperphosphorylation and preventing neuronal cell death. In an okadaic acid-induced AD mouse model, the FSMT treatment not only significantly ameliorated oxidative stress and neuroinflammation, but also improved spatial learning and memory impairments. The reduction in abnormal tau aggregation following treatment was confirmed by PET-CT imaging. Overall, this p-tau-targeted biomimetic nanocomposite demonstrated excellent biocompatibility and therapeutic efficacy, presenting a translatable strategy for treating AD and other neurological disorders through analogous mechanisms.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123970"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2026-01-04DOI: 10.1016/j.biomaterials.2026.123986
Biaobiao Wang , Jiahui Cao , Jingqiao Wu , Yiwen Zhao , Yao Zhang , Frank Abendroth , Caorui Lin , Li Zhong , Huanan Yu , Yiqi Seow , Meitong Ou , Olalla Vázquez , Lin Mei , HaiFang Yin , Gang Han
{"title":"Cardiac and skeletal muscle delivery of biotherapeutics with a blood vessel epicardial substance-targeting peptide","authors":"Biaobiao Wang , Jiahui Cao , Jingqiao Wu , Yiwen Zhao , Yao Zhang , Frank Abendroth , Caorui Lin , Li Zhong , Huanan Yu , Yiqi Seow , Meitong Ou , Olalla Vázquez , Lin Mei , HaiFang Yin , Gang Han","doi":"10.1016/j.biomaterials.2026.123986","DOIUrl":"10.1016/j.biomaterials.2026.123986","url":null,"abstract":"<div><div>Although peptide-based delivery strategies show promise for muscle and heart diseases, delivery of biotherapeutics to both skeletal and cardiac muscles remains challenging. Here, we identified a muscle-homing peptide (BV2) against blood vessel epicardial substance (BVES) by phage display. BV2 shows high binding affinity to BVES and is internalized primarily via caveolae-mediated endocytosis. Importantly, BV2 enables efficient delivery of Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomer (PMO), mCherry protein and exosomes to skeletal muscle and heart <em>in vivo</em>. BV2-mCherry protein and BV2-E31R anti-myostatin peptide were effectively delivered to muscle layers when microneedles loaded with these biotherapeutics were implanted on hindlimbs of mice. Muscle mass and myofiber size also significantly increased in muscle atrophy mice grafted with BV2-E31R microneedles. Moreover, significantly enhanced restoration of dystrophin protein was achieved in peripheral and cardiac muscles of dystrophin-deficient <em>mdx</em> and dystrophin/utrophin double-knockout mice when exosomes simultaneously modified with BV2 and PMO. These findings highlight the potency of BV2 in directing targeted delivery of diverse biotherapeutics to muscle and heart, thus providing an effective tool for DMD and other muscular and cardiac disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123986"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2026-01-03DOI: 10.1016/j.biomaterials.2026.123983
Rongguo Yu , Jiamei Xiao , Zhencheng Xiong , Xiaoyang Wu , Chaoyi Zhang , Yusheng Zhang , Kangkang Huang , Jing Sun , Hongsong Fan , Hao Liu
{"title":"Wireless magnetoelectric hydrogel spray reprograms the CXCL12-autophagy axis for spatiotemporally controlled cervical nerve root regeneration","authors":"Rongguo Yu , Jiamei Xiao , Zhencheng Xiong , Xiaoyang Wu , Chaoyi Zhang , Yusheng Zhang , Kangkang Huang , Jing Sun , Hongsong Fan , Hao Liu","doi":"10.1016/j.biomaterials.2026.123983","DOIUrl":"10.1016/j.biomaterials.2026.123983","url":null,"abstract":"<div><div>Cervical nerve root injury (CNRI) presents significant clinical challenges owing to complex anatomical constraints and poor intrinsic regenerative capacity. In this study, we introduce an <em>in situ</em>-sprayable magnetoelectric hydrogel (DG/FBD) engineered through dynamic covalent assembly and photo-triggered stabilization. The construction of critical boronate ester bonding between dopamine-modified Fe<sub>3</sub>O<sub>4</sub>@BaTiO<sub>3</sub> nanoparticles and phenylboronic acid-functionalized dextran endows DG/FBD with optimal viscosity (87 mPa s), rapid gelation (<2s) and robust tissue adhesion (22.11 kPa), allowing for precise deposition along tortuous nerve roots while conforming to branched cervical anatomy. We then establish a wireless magnetic actuation platform with conductivity modulation enabled spatiotemporally controllable bioelectronic interfacing. In CNRI models loading with magnetic stimulation, we found the hydrogel spray significantly promotes axonal regeneration and myelination, and importantly, improving functional recovery, including enhanced pain and temperature sensation, as well as increased grip strength. We also demonstrate accelerated neural differentiation of BMSCs and attenuated astrogliosis by in vitro studies. Mechanistically, we reveal that magnetoelectrically triggered CXCL12 upregulation drives Schwann cells remodeling through PI3K/AKT/mTOR inhibition and enhances autophagic flux, establishing a bioelectronic-metabolic bridge where the CXCL12-autophagy axis emerges as a fundamental regulatory node for neural regeneration. Collectively, our work pioneers wireless magnetoelectric regulation of chemokine-directed neural repair via an integrated sprayable hydrogel system that overcomes cervical interfacing constraints, establishing a promising platform for spatiotemporal microenvironmental reprogramming in complex neuropathies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123983"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-29DOI: 10.1016/j.biomaterials.2025.123967
Jianing Yi , Yuanyu Tang , Yilin Chen , Liang Chen , Dongxue Geng , Luyao Liu , Jie Yu , Lianhong Zou , Jie Zeng , Minhuan Lan , Wenjie Gao , Ming Gao
{"title":"Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy","authors":"Jianing Yi , Yuanyu Tang , Yilin Chen , Liang Chen , Dongxue Geng , Luyao Liu , Jie Yu , Lianhong Zou , Jie Zeng , Minhuan Lan , Wenjie Gao , Ming Gao","doi":"10.1016/j.biomaterials.2025.123967","DOIUrl":"10.1016/j.biomaterials.2025.123967","url":null,"abstract":"<div><div>Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root–derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as <em>Anaerostipes</em>, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota–metabolite–macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123967"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-17DOI: 10.1016/j.biomaterials.2025.123930
Jinming Cai , Sheng Shi , Jinyan Hu , Zhenlin Zhang , Bijiang Geng , Dengyu Pan , Longxiang Shen
{"title":"A stimuli-responsive cuproptosis switch boosts persistent immunotherapy for tumor eradication","authors":"Jinming Cai , Sheng Shi , Jinyan Hu , Zhenlin Zhang , Bijiang Geng , Dengyu Pan , Longxiang Shen","doi":"10.1016/j.biomaterials.2025.123930","DOIUrl":"10.1016/j.biomaterials.2025.123930","url":null,"abstract":"<div><div>Cuproptosis has been identified as a unique copper-dependent cell death mechanism that may provide new opportunities for improving tumor therapy outcomes. For currently developed cuproptosis inducers, nonspecific copper release and low levels of copper accumulation in tumors restrict their clinical applications. To precisely manage copper ion release in vivo, a <em>stimuli-responsive</em> ‘cuproptosis switch’ was designed as an intelligent platform with pH-sensitive ‘off’ and ‘on’ states, thereby inducing cancer-specific cuproptosis while guaranteeing biosecurity. A bilayer copper nanocapsule containing Cu<sub>2</sub>O and Cu<sub>2-x</sub>Se shells was demonstrated with a switch-like pH-dependent Cu<sup>+</sup> release profile across a transition pH (6.8) based on their distinct degradable properties. To boost cuproptosis-targeted therapy efficacy, the STING activating agonist MSA-2 was encapsulated in the Cu<sub>2</sub>O/Cu<sub>2-x</sub>Se nanocapsule for establishing lasting and effective immune responses. Cuproptosis-sensitization effects induced by US irradiation and MSA-2 release were elucidated, including 1) up-regulating Cu influx transporter (SLC31A1) expression and down-regulating Cu efflux transporter (ATP7A) expression to increase intracellular copper overload; 2) facilitating rapid GSH depletion for cuproptosis sensitization in the cytoplasm; 3) increasing mitochondrion membrane permeability for intracellular released Cu<sup>+</sup> ions entering the mitochondrion. The TME-specific Cu<sup>+</sup> and MSA-2 release combined with US-irradiated, spatiotemporally located ROS amplification induced tumor-specific cuproptosis, initiated immunogenic cell death, and activated cGAS-STING pathway for boosting robust and durable antitumor efficacy. As a result, complete elimination of primary and distant tumors in mice was achieved at low doses without side effects. The US-sensitized cuproptosis switch may provide opportunities for elimination of local residual tumors and abscopal metastatic foci for final tumor eradication.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123930"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomaterialsPub Date : 2026-06-01Epub Date: 2025-12-15DOI: 10.1016/j.biomaterials.2025.123906
Jie Zhou , Bin Cheng , Xu Wang , Zhengyi Xu , Ruyi Li , Jian Wang , Junyu Chen , Zhou Zhu , Weifeng Zhao , Xinting Cheng , Lin Tan , Qianbing Wan , Xibo Pei
{"title":"Antibacterial gradient-enhanced Janus self-pumping membrane for effective biofluid management and wound healing","authors":"Jie Zhou , Bin Cheng , Xu Wang , Zhengyi Xu , Ruyi Li , Jian Wang , Junyu Chen , Zhou Zhu , Weifeng Zhao , Xinting Cheng , Lin Tan , Qianbing Wan , Xibo Pei","doi":"10.1016/j.biomaterials.2025.123906","DOIUrl":"10.1016/j.biomaterials.2025.123906","url":null,"abstract":"<div><div>Optimal wound healing requires a sterile, moderately moist environment. Effective biofluid management is particularly crucial in infected skin defects, where complete drainage is essential for tissue repair. However, current dressings are largely designed for superficial injuries and fail to provide efficient fluid evacuation in deep wounds. In this study, we developed an antibiotic-loaded PAN/PCL dual-gradient Janus membrane comprising a hydrophobic macroporous outer layer, a hydrophilic microporous inner layer, and an intermediate transition layer. The membrane enables efficient self-pumping and unidirectional biofluid transport in superficial wounds. When curled into drainage strips, it enhances biofluid enrichment and supports gravity-resistant drainage in deep wounds. The superhydrophobic layer minimises cellular adhesion, reducing secondary trauma upon dressing removal. Sustained release of the incorporated antibiotic ensures prolonged antibacterial activity. In comparison with conventional clinical dressings, this Janus drainage system reduced local bacterial load by two orders of magnitude in a murine abscess model, significantly accelerating wound healing. Owing to its active drainage capacity, antibacterial efficacy, anti-adhesion properties, and biosafety, this system shows considerable potential for clinical management of infected wounds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123906"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}