{"title":"A NIR-Responsive Deep Penetration Phototherapy Strategy for Treating Infected Skin Defect via Antibacterial Effect and Inflammation Elimination.","authors":"Jinze Song, Wenxin Liu, Li Yang, Xiao Sun, Liangliang Xie, Jiawei Li, Ling Xu, Alideertu Dong","doi":"10.1002/adhm.202500987","DOIUrl":"https://doi.org/10.1002/adhm.202500987","url":null,"abstract":"<p><p>The increasing severity of antibiotic resistance and the delayed healing of infected wounds have triggered an arduous challenge that threatens human health. Instantly, quiet a few novel, efficient, and safe antibacterial strategies are urgently needed to be explored. In this study, a NIR-activated antibacterial nanocomposite (RB/UCNPs@BP) integrating rose bengal-sensitized upconversion nanoparticles (RB/UCNPs) and black phosphorus (BP) is developed for promoting infection wound healing. The photodynamic therapy (PDT) and photothermal therapy (PTT) are employed here for synergistic antibacterial action, while UCNPs further improve the penetration depth of irradiation and treatment efficiency. More importantly, the typical biodegradability of BP confers reduced resistance on nanocomposites through residual-free antimicrobial methods. The results show that RB/UCNPs@BP significantly inhibits the growth of both Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) via enhanced PDT and PTT. Besides, the infected wounds achieve better healing by accelerating fibroblast proliferation and migration, reducing inflammatory cell infiltration, and promoting neuronal regeneration and angiogenesis. This study provides a promising and anti-resistant strategy with light-triggered antibacterial and anti-inflammatory activities that can promote the regeneration of infected skin tissue.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500987"},"PeriodicalIF":10.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109189","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}
Beige Zong, Yongquan Lu, Zhongfu Li, Lian Pan, Peng Zhao, Wei Li, Kaiyong Cai
{"title":"An All-In-One Dendrobium Ionic Hydrogel with Wound Microenvironment Remodeling for Promoting Diabetic Wound Healing.","authors":"Beige Zong, Yongquan Lu, Zhongfu Li, Lian Pan, Peng Zhao, Wei Li, Kaiyong Cai","doi":"10.1002/adhm.202500611","DOIUrl":"https://doi.org/10.1002/adhm.202500611","url":null,"abstract":"<p><p>Diabetic wounds pose a complex clinical challenge due to their intricate pathological microenvironment and delayed healing process. To address this challenge, this work has developed a multifunctional all-in-one ionic hydrogel through dynamic Schiff base and amide bond crosslinking between the aldehyde groups on oxidized sodium alginate (OSA) and the amino groups on 1-(3-aminopropyl)-3-(4-vinylbenzyl) imidazole salts, in which Dendrobium officinale polysaccharides (DOP) is embedded via electrostatic interactions in the form of ionic hydrogel (OPP@DOP). The OSA and polyionic liquid enable good biocompatibility, high water containment, high swelling rate, moderate adhesion, antioxidant activity, electrical conductivity, and efficient antibacterial activity against MRSA at early stages. A sustained release of DOP is then realized and exhibits anti-inflammation, antioxidant, further promoted angiogenesis via AKT signaling pathway. These effects significantly promote re-epithelialization and collagen deposition and increase angiogenesis in wound tissue. Besides, it regulates the macrophage phenotype from the M1 subtype to the M2 subtype and reduces the expression levels of inflammatory factors, thus accelerating wound healing. The development of this multifunctional ionic hydrogel harnesses the profound potential of traditional Chinese medicine, offering a promising potential for treating diabetic wounds.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500611"},"PeriodicalIF":10.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109048","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":"Polymer-Conjugated SOD-Pt⁰ Micelles Enhance ROS Cascade Scavenging to Alleviate Ischemia-Reperfusion Injury During Kidney Transplantation.","authors":"Shengzhou Li, Fei Duan, Zhiwen Qiu, Zhuofan Nan, Xiangqian Cao, Chenkai Yang, Wei Li, Bing Shen","doi":"10.1002/adhm.202500696","DOIUrl":"https://doi.org/10.1002/adhm.202500696","url":null,"abstract":"<p><p>Ischemia-reperfusion injury (IRI) during kidney transplantation is linked to oxidative stress induced by excessive reactive oxygen species (ROS), which causes the injury of transplanted kidney, leading to further intensified organ shortages. Protein-based antioxidants have been developed for ROS scavenging via cascade biocatalyst. The in situ growth of metal nanozymes on proteins effectively decreases the steric hindrance between active sites, improving the efficiency of cascade biocatalysts. However, the poor stability of protein during the process of preparation and intracellular delivery leads to low therapeutic effects. In this study, three different functional polymers are conjugated to SOD for the formation of micelles. Surprisingly, it is found that the conjugated ultra-acid sensitive polymer efficiently preserves the enzymatic activity of SOD, due to great endo/lysosomal escape capacity. Subsequently, SOD micelles (SOE) are used as a template to prepare SOE-Pt<sup>0</sup> (SOEP) through in situ growth of Pt<sup>0</sup> with vicinal enzymatic active sites. The preparation process minimally impacts on the activity of SOD, owing to improved stability. The system exhibits effective cascade ROS scavenging, significantly reducing kidney damage and inflammation caused by IRI. The research offers a novel approach for addressing IRI challenges in organ transplantation and provides a promising strategy to mitigate organ shortages.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500696"},"PeriodicalIF":10.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109082","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}
Tongtong Zhou, Jiulong Zhou, Song Zhang, Shuxun Cui
{"title":"Flexible and Environmentally Friendly Calcium Polyphosphate Hydrogels: Toward Inorganic Functional Materials for Wearable Devices and Soft Actuators.","authors":"Tongtong Zhou, Jiulong Zhou, Song Zhang, Shuxun Cui","doi":"10.1002/adhm.202501332","DOIUrl":"https://doi.org/10.1002/adhm.202501332","url":null,"abstract":"<p><p>Inorganic hydrogels have attracted significant interest in materials science. However, it is a big challenge to fabricate flexible and multifunctional inorganic hydrogels due to the inherent rigidity of traditional inorganic materials. Herein, a flexible inorganic hydrogel is proposed, which is prepared by crosslinking long-chain polyphosphate (LPP) with Ca<sup>2+</sup> ions. This pure-inorganic CaLPP hydrogel exhibits excellent self-healing ability, arbitrarily shapable ability, conductivity, degradability and biocompatibility. Furthermore, the CaLPP hydrogel can be used as strain sensors to monitor dynamic deformations (e.g., stretching and bending) with high sensitivity and reliability. The CaLPP hydrogel can also be used as ionic skins to detect human motions, such as bending of the joints and facial expressions. After functionalization, the CaLPP hydrogel can be used as a magnetic actuator. This fundamental work provides an environmentally friendly soft material with a purely inorganic composition, which can be used as a complement to organic-based soft materials for wearable devices and actuators.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501332"},"PeriodicalIF":10.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092251","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}
Yongxin Xu, Rui Zhao, Peipei Xi, Cong Xu, Mei Yang, Junyi Che, Zhifeng Gu, Yujuan Zhu
{"title":"Engineering the Micro-Nano Hierarchical Spray Hydrogel for Acute Lung Injury Therapy.","authors":"Yongxin Xu, Rui Zhao, Peipei Xi, Cong Xu, Mei Yang, Junyi Che, Zhifeng Gu, Yujuan Zhu","doi":"10.1002/adhm.202500114","DOIUrl":"https://doi.org/10.1002/adhm.202500114","url":null,"abstract":"<p><p>Acute lung injury (ALI) poses a significant threat to human health, yet specific treatments remain elusive. Despite extensive research efforts, drug delivery to the lungs and reliable preclinical models are major challenges. To address these issues, a novel micro-nano hierarchical spray hydrogel is developed with the enhanced targeting ability for treating ALI. The hierarchical nanocomposite hydrogel is characterized with ordered micro-nanostructure, composing of spray hydrogel and astaxanthin nanoparticles (ASX-NPs). Astaxanthin, a natural active ingredient derived from algae, is nano-encapsulated to produce ASX-NPs, which significantly improves bioavailability. ASX-NPs are found to efficiently target the mitochondria and significantly relieve the inflammatory responses in human lung organoid-based inflammatory models by downregulating inflammation- and oxidative stress-related pathways and upregulating mitochondrial energy metabolism. In ALI mice, the spray hydrogel adheres to the tracheal mucosa and rapidly releases ASX-NPs upon inhalation. Released ASX-NPs are endocytosed to alleviate the inflammation and promote ALI recovery. The findings suggest that this hierarchical hydrogel system offer a promising alternative for ALI treatment, and can expand the applications of human organoids in disease modeling and drug discovery.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500114"},"PeriodicalIF":10.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092233","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}
Anran Li, Jie Li, Yufei Zhang, Ye Zhang, Yanlong Zhang, Xianhui Song, Chensheng Li, Xinge Zhang
{"title":"Enhanced Photodynamic Therapy Synergizing with Neutrophil Recruitment Boosts Drug-Resistant Bacterial Clearance.","authors":"Anran Li, Jie Li, Yufei Zhang, Ye Zhang, Yanlong Zhang, Xianhui Song, Chensheng Li, Xinge Zhang","doi":"10.1002/adhm.202500232","DOIUrl":"https://doi.org/10.1002/adhm.202500232","url":null,"abstract":"<p><p>Antibiotic-resistant bacteria produce some virulence factors as immune evasion molecules that interfere with a variety of innate immune defenses, which is associated with reduced levels of neutrophil recruitment. Antibiotics and neutrophils recruited by endogenous chemokines are not able to efficiently eliminate the bacteria at the site of infection. Here, a nano-chemoattractant (fZnCB) is developed with photodynamic therapy and neutrophil recruitment by a multi-component self-assembly strategy to coordinate benzoxaborole-modified Chlorin e6 (Ce6-BN) and formylated peptides (fMLFH) through Zn<sup>2+</sup>. This innovative system synergistically collaborates with neutrophils through photodynamic effects to combat drug-resistant bacteria. Furthermore, the nano-chemoattractant not only demonstrates exceptional bacterial adhesion properties, biofilm dispersion by photodynamic activity but also boosts the recruitment, engulfment, and killing of bacteria by neutrophils. Its remarkable therapeutic efficacy against bacterial keratitis has been validated in a mouse model. This offers a new insight into an alternate approach for treating infectious diseases caused by drug-resistant bacteria.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500232"},"PeriodicalIF":10.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092249","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":"Albumin Corona Overturns Long-Acting Behaviors of Myristic Acid-Conjugated Quetiapine Nanosuspension.","authors":"Hy Dinh Nguyen, Hai Van Ngo, Beom-Jin Lee","doi":"10.1002/adhm.202500851","DOIUrl":"https://doi.org/10.1002/adhm.202500851","url":null,"abstract":"<p><p>This work aimed to investigate the interaction of a self-assembled myristic acid-conjugated quetiapine nanosuspension (QMN) with human serum albumin and its overturning effect on QMN's long-acting performance. Albumin corona formation modified the physicochemical properties and pharmacokinetic profile of QMN by overturning its pH-responsiveness and nano-aggregation behavior. The adsorption of albumin on QMN is initially triggered by electrostatic forces and later by hydrophobic-hydrophobic interactions with the conformational change of the albumin structure. While QMN is highly susceptible to ionic strength, pH, and albumin concentration in solution, albumin-precoated QMN (A-QMN) stabilized particle size and reversed the surface charge from ≈+60 to -16 mV, annulling the pH-responsive nanoaggregation behaviors under physiological pH conditions. Consequently, A-QMNs exhibited much faster in vitro release and more rapid in vivo absorption, resulting in a huge initial burst release and shorter duration within one week in plasma concentration-time profiles compared to the extended five-week duration of QMN following intramuscular injection in beagle dogs. These findings indicated the important role of serum proteins in the release kinetics and pharmacokinetics of the nanoparticles. The manipulation of protein corona can be utilized to control the physicochemical properties, biological states, and pharmacokinetics of intended long-acting nanosuspensions.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500851"},"PeriodicalIF":10.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092228","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}
Ke Zhao, Yongzhi Cui, Yuxuan Du, Liming Zheng, Yupeng Liang, Chong Liu, Prisca Hecker, Oleksandr Moroz, Liguo Zhu, Jiawen Zhan
{"title":"Exercise Mimetic Exosomes Re-establish the Extracellular Matrix Metabolic Balance and Alleviate the Inflammatory Macrophage Infiltration in Intervertebral Disc Degeneration.","authors":"Ke Zhao, Yongzhi Cui, Yuxuan Du, Liming Zheng, Yupeng Liang, Chong Liu, Prisca Hecker, Oleksandr Moroz, Liguo Zhu, Jiawen Zhan","doi":"10.1002/adhm.202500219","DOIUrl":"https://doi.org/10.1002/adhm.202500219","url":null,"abstract":"<p><p>Extracellular matrix (ECM) metabolic imbalance and macrophage infiltration, induced by degenerated nucleus pulposus cells (NPCs), represent key pathological alterations in intervertebral disc degeneration (IVDD). Physical exercise is shown to effectively delay the progression of IVDD by enhancing ECM synthesis and reducing inflammation. However, many individuals are unable to maintain regular exercise habits due to physical limitations and insufficient self-discipline. In response to this challenge, the concept of exercise mimetic exosomes (EMEs) is proposed as a therapeutic strategy for IVDD. In this approach, human induced pluripotent stem cell-derived myotubes are subjected to mechanical strain to simulate exercise conditions. The exosomes generated under these conditions, termed EMEs, are enriched with exercise-inducible components, notably irisin. These EMEs are capable of being internalized by both NPCs and macrophages. In NPCs, EMEs restored ECM metabolic balance and inhibited NFκB activation. In macrophages, EMEs modulated the M1 polarization induced by degenerated NPCs. Collectively, EMEs restored the metabolic equilibrium of the extracellular matrix and mitigated inflammatory macrophage infiltration within the microenvironment, thereby demonstrating significant therapeutic effects on IVDD. More importantly, EMEs may serve as a model for the treatment of other musculoskeletal disorders and the development of exercise mimetic therapies.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500219"},"PeriodicalIF":10.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092250","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}
Cian O'Connor, Ian Woods, Sarah F McComish, Sean Kerr, Matthew McGrath, Juan Carlos Palomeque Chávez, Jack Maughan, Tara McGuire, Maeve A Caldwell, Adrian Dervan, Fergal J O'Brien
{"title":"Biomimetic Scaffolds Enhance iPSC Astrocyte Progenitor Angiogenic, Immunomodulatory, and Neurotrophic Capacity in a Stiffness and Matrix-Dependent Manner for Spinal Cord Repair Applications.","authors":"Cian O'Connor, Ian Woods, Sarah F McComish, Sean Kerr, Matthew McGrath, Juan Carlos Palomeque Chávez, Jack Maughan, Tara McGuire, Maeve A Caldwell, Adrian Dervan, Fergal J O'Brien","doi":"10.1002/adhm.202500830","DOIUrl":"https://doi.org/10.1002/adhm.202500830","url":null,"abstract":"<p><p>Spinal cord injury repair poses a significant challenge due to the hostile microenvironment of the injury site and the poor survival and function of clinically relevant transplanted cells. Here it is aimed to investigate whether tuning the physicochemical properties of implantable biomimetic biomaterial scaffolds can enhance the localized delivery and reparative potential of patient-derived induced pluripotent stem cells (iPSC) astrocyte progenitors. It is demonstrated that soft, collagen-IV/fibronectin-functionalized hyaluronic acid scaffolds, mimicking the physicochemical properties of healthy spinal cord tissue, optimally support the formation of iPSC-derived multicellular spheroids, promoting neural cell survival and function. These soft, collagen-IV/fibronectin scaffolds enhance angiogenic cytokine release, facilitate vascular network formation, modulate inflammatory responses, and promote neurite outgrowth from growing, mature and injured neurons, while supporting cell infiltration from spinal cord explants. These findings demonstrate that optimized biomimetic scaffold properties provide a supportive environment for iPSC astrocyte progenitors but can also modulate their reparative capacity. These findings highlight the critical role of matrix composition and scaffold stiffness in advancing scaffold-mediated patient-derived stem cell-delivery strategies for spinal cord repair applications.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500830"},"PeriodicalIF":10.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092231","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}