Maoyu Liu, Jindong Zhang, Shuning Chen, Jiao Zheng, Linlin Xiao, Xiaoli Liu, Yang Cao, Shenyin Zhu, Shufang Chang
{"title":"NIR-Triggered Metal-Polyphenol Nanoparticles Enhance HPV-Driven Cancer Immunotherapy via Immunogenic Cell Death and STING Sequential Activation.","authors":"Maoyu Liu, Jindong Zhang, Shuning Chen, Jiao Zheng, Linlin Xiao, Xiaoli Liu, Yang Cao, Shenyin Zhu, Shufang Chang","doi":"10.1002/adhm.202502884","DOIUrl":"https://doi.org/10.1002/adhm.202502884","url":null,"abstract":"<p><p>HPV-associated malignancies consistently express E6/E7 oncoproteins, making these viral antigens prime targets for therapeutic vaccination. However, insufficient antigen exposure and presentation remain major obstacles for potent immunotherapy. Here, a novel metal-polyphenol network-coated human serum albumin nanoplatform (IMT@H) is engineered to co-deliver IR780 and manganese ions (Mn<sup>2+</sup>) to achieve enhanced immunogenic cell death (ICD) and cGAS-STING-dependent antigen presentation. The metal-polyphenol nanostructure facilitates the pH-responsive release of Mn<sup>2+</sup>, which subsequently initiates Fenton-like reactions to generate hydroxyl radicals (·OH). Meanwhile, under near-infrared (NIR) light irradiation, IR780 induces mitochondrial-targeted phototherapy and concurrently produces reactive oxygen species (ROS). These processes act synergistically to amplify the oxidative damage and ICD in TC-1 tumors, leading to the release of damage-associated molecular patterns (DAMPs). These ICD-derived DAMPs cooperate with Mn<sup>2+</sup> to sustain activation of the cGAS-STING pathway in dendritic cells. This combinatorial strategy successfully transforms tumor antigens into endogenous vaccines, eventually inhibiting the growth of primary tumors and producing strong abscopal effects. Notably, mice primed with nanovaccines exhibit strong anti-HPV16 E7-specific immune responses and tumor resistance. With its dual therapeutic and preventive functionality, IMT@H represents a paradigm-shifting strategy for virus-driven malignancies and offers a blueprint for engineering self-adjuvanting nanovaccines against viral oncogenesis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02884"},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211136","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}
Alessandra Whaite, Emilie Duthoo, Mathilde Lefevre, Elise Hennebert, Patrick Flammang
{"title":"Recombinant Proteins: A Molecular Tool to Understand Marine Adhesion and to Advance Biomaterials.","authors":"Alessandra Whaite, Emilie Duthoo, Mathilde Lefevre, Elise Hennebert, Patrick Flammang","doi":"10.1002/adhm.202502340","DOIUrl":"https://doi.org/10.1002/adhm.202502340","url":null,"abstract":"<p><p>Inspiration for innovation in healthcare regularly comes from observing the natural environment. Secreted adhesives are important for marine invertebrate attachment to submerged surfaces, and these systems have inspired investigations for better performing surgical adhesives. Natural marine adhesives are fundamentally proteins, therefore, most materials research has focused on the structure and function of proteinaceous components. Omics technologies have been used to identify proteins, but these candidates require further exploration to resolve function. Functional characterization begins by producing one specific protein in larger quantities with recombinant DNA technology. Recombinant proteins (RPs) are generally seen as mimics of individual marine adhesive proteins, representing a fundamental step in the development of bio-inspired glues. The literature details production of RPs from mussels, scallops, barnacles, tubeworms, ascidians, sea anemones, and sea stars, using bacteria, yeast, or insect and mammalian cells. Whole proteins, or components thereof, have been produced comprising the relevant amino acid sequences required for adhesion and have been investigated for use in healthcare via the production of materials that push the current limits of bio-inspired design. This is a thorough review of invertebrate marine adhesives investigated using biomimetic RPs, and a comprehensive overview of the innovative biomaterials designed utilizing knowledge from biological systems.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02340"},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211146","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}
Zixi Jiang, Ziyan Chen, Huayi Wu, Kai Ye, Zhuxin Dong, Wenjihao Hu, Juan Su, Zeyu Chen, Xiang Chen, Shuang Zhao
{"title":"Synergistic Intervention of Piezo1 Activation and Fibrous Tissue Remodeling to Ease Side Effects of Intralesional Therapy for Keloids.","authors":"Zixi Jiang, Ziyan Chen, Huayi Wu, Kai Ye, Zhuxin Dong, Wenjihao Hu, Juan Su, Zeyu Chen, Xiang Chen, Shuang Zhao","doi":"10.1002/adhm.202503332","DOIUrl":"https://doi.org/10.1002/adhm.202503332","url":null,"abstract":"<p><p>Intralesional administration is the first-line therapy of keloids that can inhibit the growth of keloids and relieve patients' subjective symptoms. However, side effects, particularly pain, pose a significant challenge to injection therapy. A fractional ultrasound (FRUS) platform is developed to treat keloids and deliver drugs with minimal invasiveness and ease of operation. Keloid-bearing nude mice models are developed to investigate the in vivo effectiveness of FRUS. A pilot clinical trial is further undertaken to uncover its significancein clinical practice. This platform activated Piezo1 channels through low-frequency ultrasound, inhibiting fibroblast proliferation, and utilized the cavitation effect to remold fibrous tissues, improving drug diffusion, and finally alleviating side effects associated with injection therapy. In vivo mice experiments demonstrated that FRUS platform increased the expression of Piezo1 channels and inhibited keloids growth without causing systematic adverse events. Eight participants with keloids are enrolled in the clinical trial and treated with this approach combined with anti-keloid drugs. The findings indicated that FRUS significantly alleviated injection-associated pain by 51.9% and reduced the keloid volume. These results reveal the potential therapeutic mechanism and provide a foundation for the clinical application of this approach in enhancing keloids treatment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03332"},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211090","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}
Yang Su, Huixue Feng, Xue Yuan, Qijing Du, Hongning Jiang, Rongwei Han, Yongxin Yang, Changyong Gao, Rongbo Fan
{"title":"Progress of Micro/Nanomotors for In Vivo Biomedical Applications.","authors":"Yang Su, Huixue Feng, Xue Yuan, Qijing Du, Hongning Jiang, Rongwei Han, Yongxin Yang, Changyong Gao, Rongbo Fan","doi":"10.1002/adhm.202503935","DOIUrl":"https://doi.org/10.1002/adhm.202503935","url":null,"abstract":"<p><p>As a new-generation intelligent diagnostic and therapeutic platform, micro/nanomotors (MNMs) hold great promise for overcoming the limitations of conventional passive drug delivery systems, such as poor penetration across physiological barriers. By converting chemical, optical, acoustic, or magnetic energy into kinetic motion, MNMs enable actively propelled, targeted delivery, making them a promising emerging tool for precision medicine. This review provides a comprehensive overview of the progress in the propulsion mechanisms and motion control strategies of MNMs, emphasizing how to achieve controllable movement in vivo. The in vivo biological applications of MNMs are highlighted, including penetration of the blood-retinal barrier for ophthalmic therapies, crossing of the blood-brain barrier (BBB) for neurological interventions, targeted drug release to chronic inflammatory sites, intelligent gastrointestinal drug administration, precision thrombosis in cardiovascular diseases, and the advancement of multimodal cancer therapies. The key challenges and outlooks of MNMs for clinical translation are discussed.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03935"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197431","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}
Michael D Hunckler, Sophia Kioulaphides, Karen E Martin, Angelica L Torres, Graham F Barber, Stephen W Linderman, Rebecca S Schneider, Andrés J García
{"title":"Synthetic Hydrogels Incorporating Hydrolytic/Nonhydrolytic Macromer Ratios Exhibit Improved Tunability of In Vivo Degradation and Immune Responses.","authors":"Michael D Hunckler, Sophia Kioulaphides, Karen E Martin, Angelica L Torres, Graham F Barber, Stephen W Linderman, Rebecca S Schneider, Andrés J García","doi":"10.1002/adhm.202502475","DOIUrl":"https://doi.org/10.1002/adhm.202502475","url":null,"abstract":"<p><p>Proteolytically degradable hydrogels are widely used as delivery carriers in regenerative medicine. However, the in vivo degradation rate of these materials is difficult to control because of site-specific enzymatic activity, implant design, and disease state, impairing tissue regeneration. Hydrogels with crosslinks that degrade hydrolytically offer an alternate route to tune in vivo degradation profile. In this study, a synthetic 4-arm maleimide-terminated poly(ethylene glycol) (PEG-4MAL) hydrogel system that combines hydrolytic ester-linked PEG-4MAL (PEG-4eMAL) macromer with nondegradable amide-linked PEG-4MAL (PEG-4aMAL) macromer in various stoichiometric ratios to tune the degradability rate is engineered. The macromers are crosslinked with dithiothreitol (DTT) via thiol-maleimide click reaction. Rheological analysis shows that a family of PEG-4eMAL/PEG-4aMAL hydrogels has equivalent mechanical properties, but increasing the PEG-4eMAL content increases the rate of degradation in vitro and in vivo. PEG-4eMAL/PEG-4aMAL hydrogels support high viability of encapsulated human cells. Notably, the ratio of PEG-4eMAL/PEG-4aMAL modulates local immune cell recruitment when implanted in the subcutaneous space. These results establish the use of PEG-4eMAL/PEG-4aMAL hydrogels as a hydrolytically degradable platform to tune in vivo degradation and immune responses.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02475"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197436","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}
Donggyu Kim, Giheon Ha, Minseok Kim, Minjin Kwak, Han-Jun Kim, Junmin Lee
{"title":"Geometry-Guided Osteogenesis in Bone-on-a-Chip Systems Using Triply Periodic Minimal Surface Scaffolds.","authors":"Donggyu Kim, Giheon Ha, Minseok Kim, Minjin Kwak, Han-Jun Kim, Junmin Lee","doi":"10.1002/adhm.202502773","DOIUrl":"https://doi.org/10.1002/adhm.202502773","url":null,"abstract":"<p><p>The interplay between scaffold geometry and mechanical cues is critical in regulating osteogenesis within engineered bone microenvironments. To better mimic native bone physiology and improve regeneration strategies, it is essential to integrate precise topological control with physiologically relevant flow. Here, a bone-on-a-chip (BoC) system coupled with triply periodic minimal surface (TPMS)-based 3D scaffolds is presented to investigate how geometric parameters-pore shape and solidity-govern osteogenic responses under dynamic perfusion. Using Gyroid and Schwarz diamond TPMS architectures, scaffolds with controlled pore geometries are created to modulate wall shear stress (WSS). Under flow conditions in the BoC system, pre-osteoblasts exhibit geometry-dependent behaviors in terms of infiltration, alkaline phosphatase activity, calcium deposition, and collagen formation. Scaffolds with intermediate solidity and curvature optimize WSS distribution and significantly enhance osteogenic differentiation. Additionally, a critical pore size threshold is identified beyond which flow-mediated signaling is attenuated, highlighting the importance of geometric precision. The results demonstrate the synergistic role of scaffold topology and interstitial flow in directing osteogenesis. This integrated platform provides a versatile tool for studying bone mechanobiology and offers a promising strategy for designing biomimetic scaffolds in regenerative medicine and bone tissue engineering.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02773"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197718","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":"Correction to \"Bioprinting of Cardiac Tissue in Space: Where Are We?\"","authors":"","doi":"10.1002/adhm.202504518","DOIUrl":"https://doi.org/10.1002/adhm.202504518","url":null,"abstract":"","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04518"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197676","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}
Yueting Li, Siting Du, Yanzhen Feng, Xiaopeng Zhou, Kaiting Zhao, Jianfeng Wang, Quan Zhou, Yaru Shi, Ayesha Younas, Yonghui Shen, Shuanghu Wang
{"title":"Nitric Oxide-Enhanced Chitosan-Based Nanoparticles for Dual-Mode Photothermal and Photodynamic Therapy in Infected Wounds.","authors":"Yueting Li, Siting Du, Yanzhen Feng, Xiaopeng Zhou, Kaiting Zhao, Jianfeng Wang, Quan Zhou, Yaru Shi, Ayesha Younas, Yonghui Shen, Shuanghu Wang","doi":"10.1002/adhm.202502584","DOIUrl":"https://doi.org/10.1002/adhm.202502584","url":null,"abstract":"<p><p>Bacterial infections pose a significant challenge to global health, as conventional treatments frequently cause side effects and resistance. Phototherapy, encompassing photothermal therapy (PTT) and photodynamic therapy (PDT), emerges as a viable alternative, eradicating bacteria through heat and reactive oxygen species (ROS). However, excessive heat and ROS can exacerbate local inflammation and comlicate healing. To address these challenges, we developed a novel chitosan-based nanoparticle (NPs) encapsulating S-nitrosoglutathione (GSNO) and indocyanine green (ICG), termed as GSNO/ICG@NPs. This biocompatible nanosystem integrates the triple synergistic effects of nitric oxide (NO) release, PTT, and PDT. The stable and uniformly shaped GSNO/ICG@NPs were synthesized via a charge-driven self-assembly method with efficient loading of GSNO and ICG. Upon irradiation with an 808 nm near-infrared (NIR) laser, GSNO/ICG@NPs rapidly generate heat and <sup>1</sup>O<sub>2</sub>, effectively eliminating bacteria. Simultaneously, the photothermal effect releases NO from GSNO, modulates inflammation, promotes neovascularization, and supports tissue repair. In vitro and in vivo studies demonstrated that GSNO/ICG@NPs significantly enhance antibacterial activity, reduce inflammation, and promote angiogenesis. It effectively eradicated biofilms and accelerated wound healing in a Staphylococcus aureus-infected mouse skin model. These findings highlight GSNO/ICG@NPs as a promising alternative to antibiotics for treating infected wounds via synergistic therapy involving balanced NO release, PTT, and PDT.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02584"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197703","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 Heparin-Functionalized Scaffold with HB-EGF Immobilization for Tissue Engineering.","authors":"Bowu Peng, Huajian Chen, Chengyu Lu, Tianjiao Zeng, Man Wang, Toru Yoshitomi, Naoki Kawazoe, Yingnan Yang, Guoping Chen","doi":"10.1002/adhm.202502771","DOIUrl":"https://doi.org/10.1002/adhm.202502771","url":null,"abstract":"<p><p>The introduction of growth factors (GFs) into scaffolds to mimic the in vivo microenvironment is a promising approach for tissue engineering. In this study, a heparin-functionalized scaffold is designed to mimic the GFs reservoir function of extracellular matrix (ECM). Owing to its heparin-binding domain, heparin-binding epidermal growth factor-like growth factor (HB-EGF) is effectively and spatially captured by heparin-functionalized scaffold. Furthermore, the strong interaction between heparin and heparin-binding domain confers excellent stability of the immobilized HB-EGF in scaffold over a long period. The heparin-functionalized scaffold immobilized with HB-EGF facilitates cell adhesion and promotes proliferation of human mesenchymal stem cells (hMSCs), while not inducing their differentiation during proliferation. These results indicate that the immobilized HB-EGF has a promotive effect on proliferation of hMSCs without triggering spontaneous differentiation, and the system shows as a promising strategy to enhance stem cells proliferation in scaffolds.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02771"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197688","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}
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":"<p><p>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<sup>-1</sup> s<sup>-1</sup>. 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.</p>","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}