Bioactive Materials最新文献

{"title":"Dynamic hydrogel mechanics in organoid engineering: From matrix design to translational paradigms","authors":"Chenjia Zhang ,&nbsp;Yue Shen ,&nbsp;Mingyang Huang ,&nbsp;Guoqing Wang ,&nbsp;Qichen Miao ,&nbsp;Heping Shi ,&nbsp;Ruiqi Gao ,&nbsp;Kun Wang ,&nbsp;Ming Luo","doi":"10.1016/j.bioactmat.2025.09.021","DOIUrl":"10.1016/j.bioactmat.2025.09.021","url":null,"abstract":"<div><div>The extracellular matrix (ECM) serves as a dynamic biomechanical regulator of cellular behavior, yet conventional 3D culture systems, such as Matrigel, lack the spatiotemporal control required to dissect mechanotransductive mechanisms in organoids. This review systematically explores the synthesis of mechanically tunable hydrogels—spanning stiffness and viscoelasticity—and their transformative applications in organoid research. By integrating natural, synthetic, and hybrid polymers, these hydrogels enable precise recapitulation of tissue-specific ECM mechanics, overcoming limitations of batch variability and static properties. We categorize hydrogel design strategies, emphasizing crosslinking paradigms (physical vs. chemical) and dynamic bond engineering, which permit real-time modulation of mechanical cues. Applications across developmental organoids (intestinal, hepatic, renal, neural) reveal stiffness-dependent morphogenesis, where optimal mechanical niches enhance maturation via YAP/Notch signaling. Tumor organoid models (breast, pancreatic, colorectal) further demonstrate how matrix stiffening drives malignancy through mechanosensitive pathways, such as epithelial-mesenchymal transition and drug resistance. Emerging viscoelastic hydrogels, tailored via alginate molecular weight or decellularized ECM, replicate dynamic tissue mechanics, advancing cartilage and cerebellar organoid models. Critically, this review highlights innovations in programmable hydrogels that bridge 2D reductionist models and <em>in vivo</em> complexity, offering unprecedented insights into ECM-driven organogenesis and disease progression. Future directions include integrating bioprinting and organ-on-a-chip technologies to achieve vascularized, patient-specific organoids. By synthesizing design principles and mechanobiological mechanisms, this work establishes a roadmap for next-generation biomaterials, accelerating translational applications in drug screening, regenerative medicine, and personalized oncology.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 144-170"},"PeriodicalIF":18.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107340","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}

{"title":"Plant-derived vesicle-like nanoparticles for immunomodulation: Mechanisms and applications","authors":"Simin Wang ,&nbsp;Yanli Zhang ,&nbsp;Yuting Zeng ,&nbsp;Xin Luo ,&nbsp;Jiaping Chen ,&nbsp;Qianwen Deng ,&nbsp;Ping Xiao ,&nbsp;Ruofei Lin ,&nbsp;Xiuwen Chen ,&nbsp;Xian Ding ,&nbsp;Qianlin Li ,&nbsp;Sijie Qiu ,&nbsp;Dehong Yang ,&nbsp;Wenjuan Yan","doi":"10.1016/j.bioactmat.2025.09.024","DOIUrl":"10.1016/j.bioactmat.2025.09.024","url":null,"abstract":"<div><div>Immune dysregulation can result in sustained activation of the immune system, leading to systemic chronic inflammation. This condition significantly disrupts immune homeostasis and is intimately associated with the onset of numerous chronic systemic diseases. Currently, the treatment of diseases related to immune dysregulation confronts several challenges, most notably the substantial side effects and inconsistent efficacy of long-term immunosuppressive drug use. Consequently, developing immunomodulatory strategies that balance efficacy and safety has emerged as a prominent research focus. Plant-derived vesicle-like nanoparticles (PVLNs), natural nanomaterials secreted by plant cells, exhibit significant potential in immunomodulation owing to their excellent biocompatibility, minimal immunogenicity, and cross-species communication capabilities. This paper reviews the biogenesis, composition, and properties of PVLNs, emphasizing the mechanisms of innate and adaptive immunomodulation they mediate and their applications in diseases characterized by immune disorders. It also analyzes the challenges related to target delivery, stability optimization, drug loading, and storage encountered in their engineering. In the future, as the mechanisms of PVLNs are more deeply understood and nanotechnology continues to advance, their potential in precision immunotherapy and clinical translation is anticipated to be further augmented.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 171-204"},"PeriodicalIF":18.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107341","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}

{"title":"Mesenchymal stem cell-laden double-network hydrogel nerve guidance conduits for peripheral nerve injury repair","authors":"Junghyun Kim,&nbsp;Junggeon Park,&nbsp;Seungjun Lee,&nbsp;Chiseon Ryu,&nbsp;Jongdarm Yi,&nbsp;Goeun Choe,&nbsp;Changhan Jo,&nbsp;Jae Young Lee","doi":"10.1016/j.bioactmat.2025.08.018","DOIUrl":"10.1016/j.bioactmat.2025.08.018","url":null,"abstract":"<div><div>To enhance the repair of peripheral nerve injuries (PNIs), various nerve guidance conduits (NGCs) have been developed by integrating topological, biochemical, and cellular cues. Hydrogel-based NGCs are particularly promising owing to their unique tissue-mimicking characteristics, such as high water content, softness, and porosity. However, their weak mechanical strength and insufficient biological activity limits their application. Therefore, in this study, we aimed to develop NGCs by encapsulating human umbilical cord-derived mesenchymal stem cells (ucMSCs) in double-network (DN) hydrogel conduits for improved peripheral nerve regeneration. A DN hydrogel, fabricated via sequential photo- and ionic-crosslinking of 15 % gelatin methacrylate and 1 % alginate, exhibited excellent rheological and mechanical properties, including fatigue resistance, suture retention, and kink resistance. In a rat sciatic defect model, ucMSC-encapsulated DN NGCs demonstrated significantly improved functional and structural recovery compared to medical silicone and non-cellular hydrogel NGCs. Quantitative assessments revealed that the MSC-laden NGC group exhibited superior functional recovery, as indicated by footprint analysis, electromyography, thermal withdrawal latency, and muscle weight restoration. Moreover, histological analysis and transmission electron microscopy confirmed significantly enhanced axonal regeneration and myelination in the MSC-laden NGC group (axon diameter and myelin thickness). Overall, our results indicate that the MSC-laden hydrogel NGCs can serve as a novel platform to treat PNIs and function as effective stem cell delivery scaffolds for the regeneration of various tissues, such as the skin, tendons, and muscles.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 901-915"},"PeriodicalIF":18.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094815","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}

{"title":"An intelligent nanoreservoir system promotes heart valve regeneration via ROS scavenging and immunomodulation","authors":"Pengning Fan ,&nbsp;Yuqi Liu ,&nbsp;Xingyu Qian ,&nbsp;Jinsheng Li ,&nbsp;Yin Xu ,&nbsp;Xiang Qiu ,&nbsp;Lu Tong ,&nbsp;Fuqiang Tong ,&nbsp;Zhengfeng Fan ,&nbsp;Yidan Zheng ,&nbsp;Hanshen Luo ,&nbsp;Teng Zeng ,&nbsp;Yunbing Wang ,&nbsp;Li Xu ,&nbsp;Fei Li","doi":"10.1016/j.bioactmat.2025.09.010","DOIUrl":"10.1016/j.bioactmat.2025.09.010","url":null,"abstract":"<div><div>In situ regeneration of tissue-engineered heart valves (TEHV) is a promising strategy to overcome the limitations of existing heart valve prostheses. Although, decellularized aortic valves (DAVs) are widely regarded as a scaffold in the construction of TEHV, the poor hemocompatibility and adverse immune responses make DAV scaffolds prone to thrombosis and degradation, thus hindering recellularization and in situ regeneration. Our study developed an immune-regulatory strategy involving the use of hydrogel-encapsulated nanoparticles to modify DAV scaffolds. Specifically, folic acid- and hyaluronic acid-modified mesoporous silica nanoparticles (FA-HA-MSNs@CY-09) were engineered to deliver NOD-like receptor family, pyrin domain containing 3 (NLRP3) inhibitor CY-09, thereby targeting macrophages, modulating their polarization and establishing a pro-regenerative immune microenvironment. The reactive oxygen species (ROS)-responsive hydrogel delivering FA-HA-MSNs@CY-09 enabled intelligent nanoparticle release and ROS scavenging. Results demonstrated that the hydrogel-modified DAV scaffold exhibited ROS-responsive release of FA-HA-MSNs@CY-09, which effectively induced macrophage polarization toward the pro-remodeling M2 phenotype. In vitro, the scaffold showed favorable mechanical properties, cytocompatibility, and hemocompatibility. Transcriptome sequencing elucidated the macrophage-reprogramming mechanism of the scaffold. In vivo, the scaffolds promoted significant M2 macrophage infiltration shortly after implantation, facilitating endothelial tissue formation. This resulted in enhanced endothelialization and interstitial cell infiltration under blood flow, without thrombosis or calcification. The novel heart valve overcomes various limitations of conventional heart valve prostheses and demonstrates considerable promise for clinical translation, particularly as an immunomodulatory biomaterial strategy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 205-223"},"PeriodicalIF":18.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107343","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}

{"title":"Synergistic enhancement of efferocytosis and cholesterol efflux via macrophage biomimetic nanoparticle to attenuate atherosclerosis progression","authors":"Shiteng Cai ,&nbsp;Jinfeng Gao ,&nbsp;Xueyi Weng ,&nbsp;Zhengmin Wang ,&nbsp;Danwen Zheng ,&nbsp;Qiaozi Wang ,&nbsp;Qiyu Li ,&nbsp;Chengzhi Han ,&nbsp;Weiyan Li ,&nbsp;Jing Chen ,&nbsp;Yuyuan Fu ,&nbsp;Yiwen Tan ,&nbsp;Bohan Wei ,&nbsp;Zhiqing Pang ,&nbsp;Zheyong Huang ,&nbsp;Yanan Song ,&nbsp;Junbo Ge","doi":"10.1016/j.bioactmat.2025.09.022","DOIUrl":"10.1016/j.bioactmat.2025.09.022","url":null,"abstract":"<div><div>Atherosclerosis is the leading cause of myocardial infarction and stroke, which is characterized as a chronic inflammatory disease due to the aberrant accumulation of apoptotic cells in the necrotic core. Previous CD47-SIRPα checkpoint blockage strategies based on monoclonal antibodies or nanoparticles have shown significant pro-efferocytosis effects and thus improved the inflammatory microenvironment of plaque. However, apoptotic foam cells and concentrated cholesterol render plaque macrophages an overwhelming lipid burden, limiting the pro-efferocytosis effect of checkpoint blockade therapy in atherosclerosis. In this study, we fabricate a retinoic acid-loaded macrophage membrane-biomimetic liposome (R@MLP) to improve the efferocytosis ability of macrophages further. Mechanistically, the innate existence of SIRPα on the R@MLP would block the binding of CD47 on apoptotic cells with SIRPα on macrophages to realize the CD47-SIRPα inhibition. Consequently, engulfing retinoic acid in R@MLP would upregulate the expression of ABCA1 and ABCG1 of macrophages and enhance cholesterol efflux. In the mouse model of atherosclerosis, which benefited from the macrophage membrane, R@MLP showed ideal inflammation targeting ability to plaques and further reinforced the efferocytosis ability of macrophages. Ultimately, R@MLP shifted macrophages to the anti-inflammatory state and attenuated the progression of atherosclerosis. R@MLP synergizes checkpoint inhibition and cholesterol efflux to boost pro-efferocytosis therapy and presents a novel anti-inflammatory therapeutic strategy for atherosclerosis management.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 131-143"},"PeriodicalIF":18.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107339","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}

{"title":"Human iPSC-derived cardiac-specific extracellular matrix scaffolds for cardiomyocyte maturation and post-myocardial infarction repair","authors":"Dhavan Sharma ,&nbsp;Wenkai Jia ,&nbsp;Alvis Chiu ,&nbsp;Hee Jae Jang ,&nbsp;Vladislav Leonov ,&nbsp;Zhishi Chen ,&nbsp;Brandon Zhao ,&nbsp;Weijia Luo ,&nbsp;Hutomo Tanoto ,&nbsp;Jianhua Zhang ,&nbsp;Alexey V. Glukhov ,&nbsp;Yong Yang ,&nbsp;Yuxiao Zhou ,&nbsp;Jiang Chang ,&nbsp;Timothy J. Kamp ,&nbsp;Feng Zhao","doi":"10.1016/j.bioactmat.2025.06.044","DOIUrl":"10.1016/j.bioactmat.2025.06.044","url":null,"abstract":"<div><div>Myocardial infarction (MI) remains a leading cause of heart failure due to the limited regenerative capacity of the adult myocardium. The therapeutic efficacy of current engineered cardiac patches is hindered by their simplistic scaffold composition and lack of structural organization. This study presents a bioactive, anisotropic extracellular matrix (ECM) scaffold derived from human induced pluripotent stem cell-differentiated cardiac fibroblasts (hiPSC-CF-ECM) that combines cardiac-specific proteins and growth factors with complex structural composition. Compared to primary cardiac fibroblast ECM (pri-CF-ECM) and human dermal fibroblast ECM (hDF-ECM), hiPSC-derived cardiomyocytes (hiPSC-CMs) cultured on the cardiac-specific ECM scaffold exhibited enhanced maturation, as confirmed by bulk RNA sequencing, electrophysiological mapping, and optical-based strain analysis. In an immune-competent rat MI model, the hiPSC-CF-ECM transplantation preserved cardiac function, increased ejection fraction, and reduced maladaptive remodeling. These findings highlight hiPSC-CF-ECM as a promising biomimetic scaffold for cardiac tissue engineering and MI treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 114-130"},"PeriodicalIF":18.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107382","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}

{"title":"Bone matrix-mimetic multi-ion doped hydroxyapatite nanorod arrays for enhanced immuno-osteogenesis and prevention of aseptic loosening","authors":"Jing Ye ,&nbsp;Bo Li ,&nbsp;Meng Yu ,&nbsp;Yingang Zhang ,&nbsp;Yong Han","doi":"10.1016/j.bioactmat.2025.09.001","DOIUrl":"10.1016/j.bioactmat.2025.09.001","url":null,"abstract":"<div><div>Inflammatory responses triggered by foreign body rejection or detached wear particles are major contributors to the failure of titanium (Ti)-based orthopedic implants. One of the most common complications is aseptic loosening. To address this challenge, a nanorod-arrayed hydroxyapatite (HA) coating co-doped with multiple ions (Sr²⁺, Mg²⁺, Zn²⁺, CO₃²⁻, and SiO₄⁴⁻) was developed, to mimic the bone matrix and enhance immuno-osteogenesis. The coating exhibits strong adhesion strength and long-term interfacial stability. Ion-induced lattice distortion accelerates HA degradation, promoting the doped-ion release. These bioactive ions drive macrophage (MΦs) polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, thereby enhancing vascularized osseointegration. To evaluate the risk of aseptic loosening induced by detached nanorods, we synthesized nanorod-like particles with identical composition and morphology to those in the arrayed coating. Their effects on MΦ polarization and the underlying mechanisms were then systematically investigated. Compared to undoped particles, multi-ion doped HA nanoparticles are more easily phagocytosed and degraded within lysosomes, enabling faster ion release and thereby facilitating M1-M2 transition. Transcriptomic analysis reveals that the nanoparticle degradation-mediated ion release elevates intracellular calcium levels in MΦs, which activates antioxidant pathways and induces a metabolic shift toward fatty acid oxidation. This metabolic reprogramming subsequently activates immunoregulatory pathways, with the PPAR pathway serving as a central axis, thereby promoting M2 polarization, inhibiting osteoclastogenesis, and ultimately preventing aseptic loosening. Collectively, this study presents a coating design that not only promotes osseointegration but also retains anti-inflammatory potential even in the event of particle detachment, offering a promising strategy to mitigate aseptic loosening.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 74-93"},"PeriodicalIF":18.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107346","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}

{"title":"Dual targeting of lipid metabolic reprogramming and immunosuppressive sentinel lymph nodes potentiates anti-metastatic therapy for triple negative breast cancer","authors":"Tingting He ,&nbsp;Xuemei Liao ,&nbsp;Shuangquan Gou ,&nbsp;Genhua Liu ,&nbsp;Qiaojian Duan ,&nbsp;Zizhen Qin ,&nbsp;Junli Yang ,&nbsp;Yu Sun ,&nbsp;Peng Zhao ,&nbsp;Zhong Luo ,&nbsp;Kaiyong Cai","doi":"10.1016/j.bioactmat.2025.09.011","DOIUrl":"10.1016/j.bioactmat.2025.09.011","url":null,"abstract":"<div><div>Inducing immunogenic cell death (ICD) in cancer cells provides a promising approach in immunotherapy, however, oxidative stress relief and metabolic plasticity enhancement limit the immune-stimulating effect of traditional ICD inducer in sentinel lymph nodes (SLN), owing to the metabolism of fatty acids. In this article, a biocompatible green liposome CL-Lip was designed to not only selectively induce ICD in primary and metastatic 4T1 cells, but also relieved the immunosuppression in invasive SLN. CL-Lip is composed of engineered liposomes modified with linoleic acid and catalase, which synergistically trigger ICD, stimulate lipid peroxidation, PD-L1 carbonylation and effectively promote the maturation of dendritic cells and T cell differentiation. Moreover, catalase also downregulated the hypoxia level in SLN. Through cellular experiments and transcriptome analysis, it is proved that the ICD induction <em>via</em> CL-Lip is mediated by ROS generation, resulting from the YAP-dependent fatty acid oxidation (FAO) interference. Transcriptome analysis revealed that engineered CL-Lip diminishes YAP-dependent FAO pathway and effectively antagonizes the metabolic flexibility, thereby selectively triggering the metabolic dead-associated ICD process in both primary and metastatic 4T1 cells. In animal experiments, this little reported metabolic-driven ICD route not only significantly reduces metastatic foci, but also induces a “cold-to-hot” remodeling of SLN, resulting in the formation of a <em>in situ</em> tumor vaccine. These findings hold great significance for the development of next-generation ICD inducers and immunotherapy approaches.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 94-113"},"PeriodicalIF":18.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107338","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}

{"title":"Remodeling of senescent macrophages in synovium alleviates trauma- and aging-induced osteoarthritis","authors":"Yuhang Liu ,&nbsp;Jianan Duan ,&nbsp;Yifan Dang ,&nbsp;Ruihan Hao ,&nbsp;Hui Wang ,&nbsp;Echuan Tan ,&nbsp;Ruijue Wang ,&nbsp;Yuhan Li ,&nbsp;Song Zhang ,&nbsp;Yuanchi Wang ,&nbsp;Jia Lv ,&nbsp;Yuxin Qi ,&nbsp;Xiaoling Zhang ,&nbsp;Yiyun Cheng","doi":"10.1016/j.bioactmat.2025.09.016","DOIUrl":"10.1016/j.bioactmat.2025.09.016","url":null,"abstract":"<div><div>Osteoarthritis (OA) is one of the most concerned aging-related diseases in the worldwide, yet the investigation of immune senescence in joint and related therapies are still poorly identified. Single-cell sequencing analysis and immunofluorescence of OA synovium reveal increased senescent macrophages in trauma-induced OA compared to controls. Importantly, senescent macrophages in OA synovium showed enhanced M1 polarization, mitochondrial damage and impaired efferocytosis, which could lead to increased senescence-associated secretory phenotypes (SASPs) in the joint and further exacerbate OA. Hence, a novel senotherapeutic nanoparticle is developed using chloroquine (CQ)-bearing polymers (pCQ) for targeted delivery of superoxide dismutase (SOD) to synovial macrophages, termed as pCQ/SOD. The nanoparticle achieves efficient intracellular delivery of SOD to synovial macrophages. RNA-seq results reveal that pCQ/SOD nanoparticle inhibits macrophage senescence via p53 and cellular senescence signaling pathway, further reprograms M1-to-M2 repolarization. Furthermore, the delivered SOD inhibits BAX-dependent mitochondrial outer membrane permeabilization (MOMP) which further reduces mitochondrial DNA (mtDNA) release and SASP secretion, while pCQ promotes macrophage efferocytosis against apoptotic cells via STAT3/ADAM17/MerTK signaling. As a result, intraarticular injection of pCQ/SOD nanoparticles in mice successfully alleviates not only trauma-induced OA, but aging-induced OA as well. The developed senotherapeutic nanoparticle in this study offers an effective approach for remodeling of senescent macrophages in synovium and a promising therapeutic strategy for OA treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 42-56"},"PeriodicalIF":18.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107748","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}

{"title":"Snake-fangs-bioinspired intelligently-responsive two-stage AIE gen-containing microneedle-based platform for integrated photodynamic infected-wound management and visual therapeutic diagnosis","authors":"Lijuan Chen ,&nbsp;Xiaomin Luo ,&nbsp;Hao Yang ,&nbsp;Ying Liu ,&nbsp;Jiamin Zhang ,&nbsp;Qian Zhang ,&nbsp;Fengqian Yang ,&nbsp;Xinhua Liu ,&nbsp;Huie Jiang","doi":"10.1016/j.bioactmat.2025.09.013","DOIUrl":"10.1016/j.bioactmat.2025.09.013","url":null,"abstract":"<div><div>The efficient treatment of prevalent drug-resistant (DR) bacteria-infected wounds caused by the clinical use of conventional antibiotics remains a significant challenge. Here, a well-integrated intelligent drug-releasing, photodynamic therapy, and visual therapeutic diagnosis strategy combining burgeoning aggregation-induced emission luminogen (AIE-gen) and microneedling technology is innovatively proposed for advanced infected-wound management. This strategy is based on an intelligently responsive two-stage AIE-gen-containing microneedle-based platform (AIE-film/TS-MN) with a double-layer structure. The uppermost layer comprises an on-demand pH-responsive AIE-photosensitizer (AFPP)-based film (AIE-film). This layer is designed to achieve the precise release of reactive oxygen species (ROS) or nitrocefin, which responds to <em>β</em>-lactamase in DR bacteria. The basal layer is a two-stage microneedle (TS-MN) patch with a “core-shell” structure bio-inspired by snake fangs, providing outstanding anti-migratory origins and acid-responsive drug-releasing properties through crustaceous gelatin loaded with Fe-carbenicillin frameworks (Fe-MOF). AFPP and nitrocefin in AIE-film accurately respond to acidic wound-microenvironment and <em>β</em>-lactamase, colorfully changing from yellow and green to orange and red, respectively. This indicates that AIE-film/TS-MN exhibits significant potential as a novel biosensor to record the color-change semiquantitatively at wound-sites through smartphone analysis, visually achieving significantly infected wound-diagnosis/-assessment to facilitate the therapeutic efficacy. Additionally, the smart multiple drug-releasing synergistically eliminates DR-bacteria, including carbenicillin from Fe-MOF and AFPP-activating ROS. Comprehensive <em>in vitro</em> and <em>in vivo</em> experiments confirm that the telemedicine AIE-film/TS-MN offers advanced integrated therapeutic effects for active infected wound management. Additionally, it reduces antibiotic abuse and provides an innovative and promising strategy for visual medical diagnostics and therapeutic interventions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 886-900"},"PeriodicalIF":18.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094814","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}