{"title":"A Heterotrinuclear Ir(III)-Gd(III) Complex as a Mito-Bomb for Bimodal Imaging-Guided Precision Cancer Therapy.","authors":"Jiaxi Ru, Yu Chen, Siyi Tao, Kuang Xu, Chao Liang, Manchang Kou, Xiaoliang Tang, Weisheng Liu","doi":"10.1002/adhm.202501884","DOIUrl":"https://doi.org/10.1002/adhm.202501884","url":null,"abstract":"<p><p>Multimodal imaging-guided precision therapy has emerged as a cutting-edge theranostic strategy that integrates real-time diagnostic feedback with precision therapeutic intervention in a single platform, significantly enhancing treatment efficacy and minimizing off-target effects. Herein, Ir(III)-Gd(III) heterometallic complexes (Ir<sup>2</sup>Gd<sup>1</sup>) that exhibit exceptional mitochondrial targeting capabilities and magneto-optical bifunctional properties are designed and synthesized. As a single-molecule theranostic agent, Ir<sup>2</sup>Gd<sup>1</sup> serves as a magnetic resonance imaging (MRI) contrast agent with high relaxivity (9.42 mM<sup>-1</sup> s<sup>-1</sup>), while its intrinsic phosphorescence facilitates both optical imaging and phototherapy. Notably, Ir<sup>2</sup>Gd<sup>1</sup> can selectively accumulate within cancer cell mitochondria. Upon light irradiation, it generates singlet oxygen, which disrupts mitochondrial integrity by inducing cytochrome c release, thereby activating apoptosis or pyroptosis pathways. Additionally, Ir<sup>2</sup>Gd<sup>1</sup> photocatalytically oxidizes NADH, disrupting the mitochondrial electron transport chain and depleting ATP, further impairing cellular energy metabolism. Mechanistic investigations further reveal that Ir<sup>2</sup>Gd<sup>1</sup> activates the caspase-3/GSDME signaling axis to induce pyroptosis, a mechanism crucial for overcoming apoptosis resistance and triggering anti-tumor immune responses. Collectively, Ir<sup>2</sup>Gd<sup>1</sup> functions as a \"Mito-Bomb\" that targets cancer cells' central powerhouse, executing focused detonation to achieve potent antitumor efficacy. This study presents a novel single-molecule theranostic tool for tumor phototherapy and pyroptosis guided by magneto-optical dual-modal imaging.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01884"},"PeriodicalIF":9.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336303","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}
Ziyang Zhang, Yichuan Ma, Zhengxin Yu, Yan Jin, Ying Yang, Mengmeng Ji, Hua Yang, Guang Jia, Jinchao Zhang, Zhenhua Li, Huifang Liu
{"title":"Monocyte Backpack Delivery of Engineered MCF-7 Exosomes for the Treatment of Early Stage Type 1 Diabetes.","authors":"Ziyang Zhang, Yichuan Ma, Zhengxin Yu, Yan Jin, Ying Yang, Mengmeng Ji, Hua Yang, Guang Jia, Jinchao Zhang, Zhenhua Li, Huifang Liu","doi":"10.1002/adhm.202503453","DOIUrl":"https://doi.org/10.1002/adhm.202503453","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by autoimmune-mediated destruction of pancreatic β-cells through cytotoxic T lymphocyte infiltration, leading to absolute insulin deficiency. Supplementation of exogenous insulin can't protect remaining β-cells or address the root autoimmune cause. The emerging therapeutic strategies focus on immunomodulatory approaches, targeting the activation of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway could attenuate T cell-mediated β-cell destruction, thereby alleviating inflammation in early-stage T1DM. However, nonselective PD-1/PD-L1 blockade can cause toxicity. Herein, exosomes from PD-L1<sup>high</sup> MCF-7 cells are utilized, modified with monocyte-targeting IgG, and have their contents removed via electroporation to eliminate tumorigenicity. Monocytes have the characteristic of targeting inflammatory sites. rExo-IgG is stably anchored to the monocytes' membrane through IgG and transported as a backpack of monocytes to the inflammatory sites (pancreas and wounds). In the pancreatic tissue, rExo-IgG through PD-1/PD-L1 pathway, inhibiting their activation and protecting β-cells. At the site of tissue injury, rExo-IgG repolarizes macrophages from pro-inflammatory M1 to anti-inflammatory M2. It also promotes fibroblast proliferation and migration, enhancing tissue regeneration. This dual-targeting exosome platform not only exhibits therapeutic efficacy against early-stage T1DM but also offers a novel strategy for the treatment of diabetic wound healing disorders.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03453"},"PeriodicalIF":9.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336298","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}
Liyan Zhang, Peiyuan Wang, Hildert Bronkhorst, Yurii Husiev, Ludovic Bretin, Maarten N van Ginkel, Wen Sun, Sylvestre Bonnet
{"title":"Photoactivated Proximity Protein Labeling Reveals Enhanced Tumor Retention of a D-Peptide-Ruthenium Prodrug Conjugate.","authors":"Liyan Zhang, Peiyuan Wang, Hildert Bronkhorst, Yurii Husiev, Ludovic Bretin, Maarten N van Ginkel, Wen Sun, Sylvestre Bonnet","doi":"10.1002/adhm.202502174","DOIUrl":"https://doi.org/10.1002/adhm.202502174","url":null,"abstract":"<p><p>Amino acid chirality is known to influence the biological properties of peptide-containing prodrugs. In this work, both Δ and Λ isomers of three cyclic ruthenium-peptide photoactivated chemotherapy (PACT) conjugates [1]Cl<sub>2</sub>-[3]Cl<sub>2</sub> are prepared that bear the bidentate peptide Ac-MRGDM-NH<sub>2</sub>, Ac-mrGdm-NH<sub>2</sub>, or Ac-MrGdM-NH<sub>2</sub>, respectively, where M, R, and D are L-amino acids and m, r, and d are their D-isomers. All six PACT compounds show low dark cytotoxicity (EC<sub>50,dark</sub> > 30 µM) toward normoxic (21% O<sub>2</sub>) and hypoxic (1% O<sub>2</sub>) A549 human lung cancer cells. Upon green light irradiation, the peptide is cleaved off via an efficient two-step photosubstitution reaction, which raises the cytotoxicity up to 20-fold in normoxia and 4.5-fold in hypoxia. The Λ-[1]Cl<sub>2</sub>, Λ-[2]Cl<sub>2</sub> and Λ-[3]Cl<sub>2</sub> isomers are further studied in A549 human lung xenograft in mice. Strikingly, the D-peptide conjugate Λ-[2]Cl<sub>2</sub> has higher antitumor activity than the two other isomers. For the first time, the fate of the photoactivated PACT prodrug can be tracked in vivo via red phosphorescence resulting from proximity labeling of histidine-containing proteins. Photoactivated Λ-[2]Cl<sub>2</sub> shows higher tumor retention and better clearance from the rest of the body, thereby explaining the excellent antitumor properties of this PACT compound.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02174"},"PeriodicalIF":9.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335999","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}
Farzaneh Sabbagh, Anna Zakrzewska, Daniel Rybak, Julia Król, Asad Abdi, Paweł Nakielski, Filippo Pierini
{"title":"Transdermal Drug Delivery Systems Powered by Artificial Intelligence.","authors":"Farzaneh Sabbagh, Anna Zakrzewska, Daniel Rybak, Julia Król, Asad Abdi, Paweł Nakielski, Filippo Pierini","doi":"10.1002/adhm.202503030","DOIUrl":"https://doi.org/10.1002/adhm.202503030","url":null,"abstract":"<p><p>Transdermal drug delivery systems (TDDSs) offer non-invasive therapy but face persistent challenges. Artificial intelligence (AI) transforms TDDSs by leveraging machine learning (ML) and predictive analytics to address these barriers. ML models predict drug entrapment with 93.0% accuracy, streamlining development. AI enhances transdermal patch formulations by forecasting drug release kinetics, skin penetration, and stability, minimizing reliance on costly clinical trials. Through virtual screening, AI identifies novel drug candidates and permeation enhancers, accelerating innovation. In microneedle systems, AI optimizes geometries, materials, and drug loading, improving precision and personalization. AI-integrated biosensors enable real-time monitoring, supporting adaptive dosing tailored to individual physiological profiles. Compared to traditional modeling, AI provides superior accuracy and scalability, handling complex datasets to reveal non-linear relationships. Despite challenges like data quality and privacy concerns, AI's integration with 3-dimensional printing and stimuli-responsive materials drives the development of personalized, efficient transdermal therapies. This perspective highlights AI's critical role in advancing therapeutic efficacy and patient-centric care in TDDSs, uniquely combining predictive modeling with real-time monitoring to envision next-generation personalized transdermal delivery systems.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03030"},"PeriodicalIF":9.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306422","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}
Sera Lindner, Stefan Keim, Soheil Haddadzadegan, Odile Fernandez Romero, Katrin Zöller, Gabriel Stern, Ilaria Cesi, Krum Kafedjiiski, Andreas Bernkop-Schnürch
{"title":"Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs.","authors":"Sera Lindner, Stefan Keim, Soheil Haddadzadegan, Odile Fernandez Romero, Katrin Zöller, Gabriel Stern, Ilaria Cesi, Krum Kafedjiiski, Andreas Bernkop-Schnürch","doi":"10.1002/adhm.202503721","DOIUrl":"https://doi.org/10.1002/adhm.202503721","url":null,"abstract":"<p><p>Macromolecular drugs, including peptides, proteins, oligonucleotides, and polysaccharides, have shown remarkable therapeutic potential due to their high specificity, potency, and low toxicity profiles. However, their clinical translation, particularly for oral administration, remains limited by poor bioavailability arising from poor membrane permeability and enzymatic instability. Enhancing the lipophilicity of these molecules is a critical strategy to overcome these challenges, improving their membrane permeability, stability, and pharmacokinetic properties. This review discusses current strategies to improve the lipophilicity of macromolecular drugs, focusing on covalent and non-covalent lipidation. Covalent lipidation, which involves the conjugation of lipids such as fatty acids or steroids, provides stable chemical modifications that have led to several commercially successful products. However, it also presents regulatory complexities due to the formation of new active pharmaceutical ingredients. In contrast, non-covalent lipidation methods, such as hydrophobic ion pairing and reverse micelle formation, offer reversible alternatives that preserve the native structure of the drug, simplify regulatory procedures, and allow flexible tuning of delivery properties. Notably, reverse micelle systems demonstrate superior performance compared to hydrophobic ion pairs, particularly in enhancing the lipophilicity of larger, more complex macromolecules. While lipidation strategies have significantly advanced the field, substantial challenges remain, especially in achieving consistent bioavailability and translating preclinical success into clinical efficacy. Future progress will require innovative ideas and the integration of emerging technologies to fully unlock the potential of lipidated macromolecular therapeutics.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03721"},"PeriodicalIF":9.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297793","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":"Vibration-Mediated Recovery of Irradiated Osteocytes and Their Regulatory Role in Breast Cancer Bone Metastasis.","authors":"Xin Song, Kimberly Seaman, Amel Sassi, Chun-Yu Lin, Tiankuo Chu, Liyun Wang, Yu Sun, Lidan You","doi":"10.1002/adhm.202501689","DOIUrl":"https://doi.org/10.1002/adhm.202501689","url":null,"abstract":"<p><p>Radiotherapy is a cornerstone of breast cancer treatment, but it can unintentionally damage bone, causing bone loss and pain, with no currently effective therapeutic strategy available. While chemically mediated radioprotection is extensively studied, mechanically mediated radioprotection remains underexplored. Given its safety and efficacy, this work examines the potential of low-magnitude, high-frequency (LMHF) vibration as a non-invasive intervention to protect irradiated bone, focusing on osteocytes-the primary mechanosensors and regulators whose functions extend to modulating breast cancer bone metastasis. These results demonstrate that LMHF vibration (0.3 g, 60 Hz, 1 h) mitigates osteocyte apoptosis and upregulates cytoskeletal markers following 8 Gy irradiation. LMHF vibration applied 1 h per day over 3 days restores the regulatory function of irradiated osteocytes in controlling breast cancer extravasation in a microfluidic platform. A combined approach integrating vibration with radiotherapy further reduces cancer invasion and extravasation, demonstrating a compound effect. RNA sequencing (RNA-seq) analysis reveals that this osteocyte-mediated regulation is possibly driven by the Wnt signaling pathway. These findings highlight the potential of LMHF vibration in enhancing radiotherapy efficacy by protecting osteocytes and reducing breast cancer metastasis, underscoring the promise of a non-invasive mechanical intervention in preserving bone health and optimizing cancer treatment outcomes.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01689"},"PeriodicalIF":9.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297853","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":"Oral Administration of Trifluoroacetyl Chitosan-Encapsulated Redshifted Immunofluorophore for NIR-II Bioimaging of Colorectal Metastases.","authors":"Yibing Shi, Xiaoyi Zhu, Qingyuan Xu, Yanling Wu, Yishuo Sun, Xin Zhao, Yulong Liu, Wei Feng, Youhua Xie, Tianlei Ying, Zhenlin Yang","doi":"10.1002/adhm.202501877","DOIUrl":"https://doi.org/10.1002/adhm.202501877","url":null,"abstract":"<p><p>The oral administration of immunofluorophores has been limited by gastrointestinal degradation. To address this, a novel immunofluorophore (ICGM-B9-FCS), based on a single-domain antibody-dye targeting the CEACAM5 antigen, is coated with trifluoromethyl chitosan (5 mg kg<sup>-1</sup>) for NIR-II bioimaging of colorectal cancer and its distant metastases. ICGM-B9-FCS demonstrates unique advantages over existing intraoperative tumor-guidance bioagents, including resistance to liver metabolism, well-retained bioaffinity (EC<sub>50</sub> = 58.09 nmol L<sup>-1</sup>), enhanced relative quantum yield (up to 12 equivalents), significant redshifts in absorption (from 783 to 957 nm), effective oral delivery to colonic metastases, and in situ exploration of the capillary-lymphatic network transportation. These findings establish a regulatory pathway for modifying immunofluorophores as orally administered bioagents, offering innovative methods for preoperative diagnosis and intraoperative guidance in colorectal cancer.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01877"},"PeriodicalIF":9.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297838","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}
Yi Liu, Xujie Cui, Minhao Guo, Jinmei Wu, Yulan Zhao, Guangzheng Zhang, Jiahui Xu, Heyou Han, Weihui Li, Zhiyong Song
{"title":"Microenvironment-Responsive Cu-MOF Nanoplatform Activates Disulfiram for Synergistic Bacterial Killing and Enhanced Infected Wound Healing.","authors":"Yi Liu, Xujie Cui, Minhao Guo, Jinmei Wu, Yulan Zhao, Guangzheng Zhang, Jiahui Xu, Heyou Han, Weihui Li, Zhiyong Song","doi":"10.1002/adhm.202503594","DOIUrl":"https://doi.org/10.1002/adhm.202503594","url":null,"abstract":"<p><p>Drug-resistant bacterial infections pose a significant threat to global health, creating an urgent need for new antimicrobial agents. Reusing approved drugs has gained attention as a strategy to address this issue. In this study, a nano antibacterial platform (DSF@HKUST-1@Dex) that responds to the infection microenvironment is proposed. This platform releases disulfiram (DSF), binds to copper ions in the mildly acidic conditions of infected areas, converting DSF from nontoxic to toxic in situ, thereby inducing bacterial death and enhancing copper ion absorption. Noncatalytic treatment is also initiated for a synergistic antibacterial effect. Excessive copper ions disrupt bacterial metabolism, inhibit the Tricarboxylic acid (TCA) cycle, reduce ATP levels, and induce cuproptosis-like death, significantly enhancing antibacterial efficacy. In a bacterial wound infection model, the platform exhibited excellent antibacterial activity, promoting wound healing and reducing inflammation. Proteomic analysis showed that the platform selectively targeted bacterial peptidoglycan, disrupted the bacterial cell wall, impacted energy metabolism, and inhibited bacterial growth. In conclusion, this nanoplatform offers a promising strategy for treating drug-resistant infections by repurposing old drugs, converting them to toxic forms, and providing a novel antimicrobial approach.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03594"},"PeriodicalIF":9.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297783","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":"Optimized Bio-Based Polyurethane Structure for Enhanced Durability and Biocompatibility in Artificial Ligaments.","authors":"Jiamei Fu, Mengqiu Quan, Haiquan Sun, Junyi Zhou, Qingyi Xie, Minghui Cui, Xiaolin Wang, Fenglong Li, Jin Zhu, Jing Chen","doi":"10.1002/adhm.202503953","DOIUrl":"https://doi.org/10.1002/adhm.202503953","url":null,"abstract":"<p><p>In the field of sports medicine, especially in high-intensity sports such as football, basketball, and skiing, ligament injuries are extremely common. However, current artificial ligaments face multiple critical limitations, including suboptimal biocompatibility, limited host tissue integration, insufficient mechanical durability to withstand physiological stresses, and inadequate durability during long-term cyclic loading. To address these challenges, 1-(2-Hydroxyphenyl)-3-phenyl-2-propenone (HCC), which shared structural similarity with naturally occurring chalcones, is employed as the raw material for the chain extender, combined with HMDI and polycaprolactone diol (PCL diol), to synthesize a novel polyurethane (HCMPU). The results showed that the maximum stress of HCMPU-3 reached 42.1 MPa, with an elongation at break of up to 710%. It also demonstrated outstanding durability, maintaining structural integrity without significant degradation after 5000 loading cycles. Additionally, during the initial implantation period, its stability in an enzymatic environment can provide strong support to the human body before new tissue regeneration, making it a promising candidate for an ideal artificial ligament. Moreover, the favorable biocompatibility of HCMPUs is demonstrated through cytotoxicity testing and rat pathological staining sections. Therefore, this work demonstrated the potential of HCMPU to overcome key limitations in current artificial ligaments and advance the development of next-generation materials for ligament repair.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03953"},"PeriodicalIF":9.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297780","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}
Wenqing Chen, Wei Huang, Rohit Gupta, Abbas Heydari, Biswajoy Bagchi, Lulu Xu, Yang Xue, Eirini Velliou, Manish K Tiwari
{"title":"Transparent Multifunctional Wearable Strain Sensor With Self-Healing and Antibacterial Capabilities for Human Motion Detection.","authors":"Wenqing Chen, Wei Huang, Rohit Gupta, Abbas Heydari, Biswajoy Bagchi, Lulu Xu, Yang Xue, Eirini Velliou, Manish K Tiwari","doi":"10.1002/adhm.202503689","DOIUrl":"https://doi.org/10.1002/adhm.202503689","url":null,"abstract":"<p><p>Wearable strain sensors are highly desirable due to their increasing applications in smart electronic skins and healthcare monitoring systems. Nevertheless, simultaneously integrating high stretchability, sensing linearity, stable operation under sub-zero temperatures, and long-term storage for conductive films remains a formidable challenge. Herein, a dual-network polyvinyl alcohol (PVA)-based high-performance strain sensor that overcomes these limitations through an innovative materials design is reported. The network is constructed via synergistic cross-linking of PVA with tannic acid (TA) and glutaraldehyde (GA), followed by the incorporation of choline acetate ionic liquid (IL) to enhance the multifunctionality of the sensor (denoted as PTGIL). The PTGIL sensor exhibits a compelling combination of properties, such as exceptional mechanical robustness (strength ≈20 MPa; elongation at break ≈900%), room-temperature self-healing capability, and transparency (≈88% transmittance at 550 nm). Critically, it demonstrates stable sensing performance even at sub-zero temperatures and preserves functionality after long-term ambient storage. The biocompatibility with human dermal fibroblasts and the antimicrobial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) confirm its safety and further support long-term skin contact applications. Beyond conventional motion monitoring, the multifunctionality of the PTGIL sensor may help bridge soft biomechanics and healthcare applications such as rehabilitation tracking following joint ligament reconstruction and intraoperative motion-outcome correlation analysis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03689"},"PeriodicalIF":9.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290347","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}