Bioactive Materials最新文献

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ATP-fueled STING activation of manganese coordinated nanoagonist to boost antitumor immunity atp介导的锰协同纳米激动剂的STING活化增强抗肿瘤免疫
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-07-01 Epub Date: 2026-02-10 DOI: 10.1016/j.bioactmat.2026.02.012
Si-Yao Han , Sui-Juan Zheng , Jia-Qi Luo , Hui-Han Yu , Xiao-Yue Liu , Jin-Zhi Du
{"title":"ATP-fueled STING activation of manganese coordinated nanoagonist to boost antitumor immunity","authors":"Si-Yao Han ,&nbsp;Sui-Juan Zheng ,&nbsp;Jia-Qi Luo ,&nbsp;Hui-Han Yu ,&nbsp;Xiao-Yue Liu ,&nbsp;Jin-Zhi Du","doi":"10.1016/j.bioactmat.2026.02.012","DOIUrl":"10.1016/j.bioactmat.2026.02.012","url":null,"abstract":"<div><div>The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway represents a central driver of innate immune activation, and manganese ion (Mn<sup>2+</sup>) has recently been identified as a potent modulator of this signaling axis. However, the application of Mn<sup>2+</sup> is limited by its rapid clearance, nonspecific distribution and potential neurotoxicity. Inspired by the unique chemical structure and biological functions of adenosine triphosphate (ATP), we herein propose an ATP-Mn coordination nanoparticle (ATP-Mn CNP) to fuel cGAS-STING activation and antitumor immunity. We demonstrated that the phosphate groups of ATP could coordinate with Mn<sup>2+</sup> and form stable, well-defined nanoparticles after lipid coating. ATP-Mn CNP significantly increased the expression of cGAS-STING-associated genes and activated the corresponding signaling cascades, and thus effectively polarized macrophages from tumor-supportive M2 to antitumor M1 phenotype. <em>In vivo</em> antitumor studies indicated that ATP-Mn CNP treatment significantly suppressed tumor growth, and reprogramed macrophages in tumors and draining lymph nodes, which thus facilitated the tumor infiltration of cytotoxic lymphocytes. Combination of ATP-Mn CNP with immune checkpoint inhibitors achieved 37.5% tumor eradication in MC38 murine models, and significantly prolonged mice survival. This study establishes an ATP-fueled coordination strategy that harnesses ATP as both an assembly ligand and an immune stimulator to enhance Mn-mediated STING activation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 107-120"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172434","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}
引用次数: 0
Artificial intelligence virtual extracellular vesicles (AIVEVs) 人工智能虚拟细胞外囊泡(aivev)
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-07-01 Epub Date: 2026-02-09 DOI: 10.1016/j.bioactmat.2025.12.050
Han Liu , Shiyu Li , Jian Wang , Jiacan Su
{"title":"Artificial intelligence virtual extracellular vesicles (AIVEVs)","authors":"Han Liu ,&nbsp;Shiyu Li ,&nbsp;Jian Wang ,&nbsp;Jiacan Su","doi":"10.1016/j.bioactmat.2025.12.050","DOIUrl":"10.1016/j.bioactmat.2025.12.050","url":null,"abstract":"<div><div>Recent progress in artificial intelligence (AI) has given rise to AI virtual cells (AIVCs), which are digital twins of predictable or dynamic biological cells. This model can simulate, predict and replicate the behavior of real cells in digital software. Extracellular vesicles (EVs) are nanoscale phospholipid bilayer structures released by cells and are important for intercellular communication. To fully leverage digital models in EVs research, we propose the interdisciplinary concept of AI virtual EVs (AIVEVs). This review systematically outlines the construction of AIVEVs through both knowledge-driven (white-box) and data-driven (black-box) modeling paradigms, integrating multi-omics data to simulate EVs biogenesis, cargo sorting, and intercellular communication. Moreover, we highlight how AIVCs drive models to predict the composition of AIVEVs, analyze cell communication behavior, construct diagnostic atlases of pathological virtual cells, and enhance the ability to trace vesicle origins. Furthermore, we also present a closed-loop workflow from <em>in silico</em> prediction to experimental validation and project the developmental trajectory of AIVEVs toward clinical translation. We firmly believe that AIVEVs can accelerate the development of EVs-based disease diagnosis and treatment, thereby opening a new era of intercellular communication research.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 34-55"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172433","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}
引用次数: 0
Dynamic hydrogels orchestrate the differentiation fate of mesenchymal stem cells through epigenetic regulation of SETD7 to accelerate bone defect repair 动态水凝胶通过表观遗传调控SETD7调控间充质干细胞的分化命运,加速骨缺损修复
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-07-01 Epub Date: 2026-02-11 DOI: 10.1016/j.bioactmat.2026.01.019
Xudong Xie , Liangcong Hu , Yueman Zhang , Bobin Mi , Xiaoyue Xu , Chong Ding , Yiming Li , Fawwaz Al-Smadi , Xiangyu Chu , Yuan Xiong , Kunyu Zhang , Liming Bian , Guohui Liu
{"title":"Dynamic hydrogels orchestrate the differentiation fate of mesenchymal stem cells through epigenetic regulation of SETD7 to accelerate bone defect repair","authors":"Xudong Xie ,&nbsp;Liangcong Hu ,&nbsp;Yueman Zhang ,&nbsp;Bobin Mi ,&nbsp;Xiaoyue Xu ,&nbsp;Chong Ding ,&nbsp;Yiming Li ,&nbsp;Fawwaz Al-Smadi ,&nbsp;Xiangyu Chu ,&nbsp;Yuan Xiong ,&nbsp;Kunyu Zhang ,&nbsp;Liming Bian ,&nbsp;Guohui Liu","doi":"10.1016/j.bioactmat.2026.01.019","DOIUrl":"10.1016/j.bioactmat.2026.01.019","url":null,"abstract":"<div><div>Dynamic mechanical signaling of the extracellular matrix is a key determinant of mesenchymal stem cell (MSC) fate, closely regulating their proliferation, differentiation and migration. Previously, we developed a highly cell-adaptive dynamic hydrogel (HA-ADA) that modulates MSC fate through unknown mechanisms. Here, using human bone marrow-derived mesenchymal stem cells (hMSCs), we found that sustained mechanical stimulation provided by HA-ADA hydrogel induced rapid spreading and significantly enhanced their osteogenic differentiation while inhibiting adipogenesis. Mechanistically, miRNA sequencing revealed that this process was mediated by the downregulation of miR-376a-3p and miR-127-5p, thereby relieving their inhibitory effect on the methyltransferase SETD7. Elevated SETD7 expression catalyzed methylation of β-catenin and accelerated its nuclear translocation. In the nucleus, β-catenin further formed a transcriptional complex with YAP to synergistically amplify downstream signals and potently activate the expression of Runx2, a key transcription factor for osteogenesis, which ultimately drove osteogenic differentiation and inhibited adipogenesis. The present study elucidated a novel mechanism by which cell-adaptive hydrogels regulate the β-catenin/YAP signaling loop through the miR-376a-3p/miR-127-5p-SETD7 axis, thereby determining the osteogenic/adipogenic differentiation of stem cells, which not only deepens our understanding of mechanotransduction but also provides new targets and material design strategies for bone regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 136-149"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172468","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}
引用次数: 0
Polyplex of peptide-mannan and RNA for intranasal delivery of TGF-β siRNA in treatment of pulmonary fibrosis 多肽甘露聚糖与RNA复合用于TGF-β siRNA鼻内递送治疗肺纤维化
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-07-01 Epub Date: 2026-02-06 DOI: 10.1016/j.bioactmat.2026.02.006
Bailin Feng , Abhalaxmi Singh , Yiqing Yang , Philana Phan , Han Xu , Yuli Zhu , Jennifer Huang , Vrushank Sastry , Zongmin Zhao , Ying S. Hu , Gang Cheng , Asrar B. Malik , Ying Liu
{"title":"Polyplex of peptide-mannan and RNA for intranasal delivery of TGF-β siRNA in treatment of pulmonary fibrosis","authors":"Bailin Feng ,&nbsp;Abhalaxmi Singh ,&nbsp;Yiqing Yang ,&nbsp;Philana Phan ,&nbsp;Han Xu ,&nbsp;Yuli Zhu ,&nbsp;Jennifer Huang ,&nbsp;Vrushank Sastry ,&nbsp;Zongmin Zhao ,&nbsp;Ying S. Hu ,&nbsp;Gang Cheng ,&nbsp;Asrar B. Malik ,&nbsp;Ying Liu","doi":"10.1016/j.bioactmat.2026.02.006","DOIUrl":"10.1016/j.bioactmat.2026.02.006","url":null,"abstract":"<div><div>Pulmonary fibrosis is a progressive, severe respiratory disease, often considered terminal, with a typical life expectancy of only a few years. It is marked by excessive deposition of extracellular matrix proteins, driven by a complex interplay of profibrotic signaling pathways, including contributions from monocyte-derived alveolar macrophages (Mo-AMs) and various immune and stromal cells. In this study, we present a peptide-mannan conjugate nanoparticle (PMNP) platform for the targeted delivery of transforming growth factor-β small interfering RNA (TGF-β siRNA) aimed at halting and reversing pulmonary fibrosis. The nanoparticles of TGF-β siRNA and peptide-mannan conjugates, generated through a solvent-free and easily scalable process, were administered intranasally to specifically target the alveolar macrophage population. In fibrotic models, these nanoparticles effectively reduced Mo-AM infiltration, reprogrammed the macrophage phenotype, and significantly reduced collagen deposition. Our findings suggest that intranasal delivery of TGF-β siRNA via PMNP offers a promising, easily self-assembled, and patient-friendly therapeutic approach for the treatment of lung fibrosis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 20-33"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172496","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}
引用次数: 0
Enzyme responsive antimicrobial hyaluronan-nanocellulose hybrid wound dressings for the treatment of infected wounds 酶反应抗菌透明质酸-纳米纤维素复合伤口敷料用于治疗感染伤口
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-07-01 Epub Date: 2026-02-11 DOI: 10.1016/j.bioactmat.2026.01.042
Elisa Zattarin , Wasihun Bekele Kebede , Zeljana Sotra , Rozalin Shamasha , Annika Starkenberg , Valentina Guerrero-Florez , Lalit Pramod Khare , Torbjörn Bengtsson , Hazem Khalaf , Emma M. Björk , Jonathan Rakar , Johan P.E. Junker , Daniel Aili
{"title":"Enzyme responsive antimicrobial hyaluronan-nanocellulose hybrid wound dressings for the treatment of infected wounds","authors":"Elisa Zattarin ,&nbsp;Wasihun Bekele Kebede ,&nbsp;Zeljana Sotra ,&nbsp;Rozalin Shamasha ,&nbsp;Annika Starkenberg ,&nbsp;Valentina Guerrero-Florez ,&nbsp;Lalit Pramod Khare ,&nbsp;Torbjörn Bengtsson ,&nbsp;Hazem Khalaf ,&nbsp;Emma M. Björk ,&nbsp;Jonathan Rakar ,&nbsp;Johan P.E. Junker ,&nbsp;Daniel Aili","doi":"10.1016/j.bioactmat.2026.01.042","DOIUrl":"10.1016/j.bioactmat.2026.01.042","url":null,"abstract":"<div><div>Wound infections pose a substantial clinical challenge and an escalating healthcare burden, further complicated by the rapid increase in multidrug-resistant bacteria. Antimicrobial peptides (AMPs) offer an alternative to conventional antibiotics, but their rapid degradation, hemolytic activity, and potential cytotoxicity complicate systemic delivery and can have negative impact on wound healing. Here we show a bacterial nanocellulose hyaluronan (BC-HA) hybrid hydrogel wound dressing functionalized with mesoporous silica nanoparticles (MSNs) for localized, enzyme responsive delivery of a sequence optimized antimicrobial peptide (SOAP) for treatment of infected wounds. The dressings provide moisture retention and excellent skin conformability while enabling infection-triggered AMP release by bacterial and host proteases. <em>In vitro</em>, SOAP-loaded dressings showed potent activity against clinical wound pathogens while remaining compatible with human primary dermal fibroblasts and keratinocytes. In a contaminated porcine wound model, the dressings significantly reduced bacterial load while accelerating wound re-epithelialization and epithelial maturation compared to the controls. By integrating a dual-function hydrogel that promotes healing and provides on-demand antimicrobial activity, critical limitations in the use of AMPs in wound care can be addressed, providing new possibilities to treat infected wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 150-171"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172416","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}
引用次数: 0
Geometry-driven immunomodulation in 3D-printed bioceramics: Negative curvature promotes macrophage M2 polarization via Ras-MAPK/HIF-1α signaling for vascularized osteogenesis 3d打印生物陶瓷中的几何驱动免疫调节:负曲率通过Ras-MAPK/HIF-1α信号促进巨噬细胞M2极化,促进血管化成骨
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-06-01 Epub Date: 2026-01-28 DOI: 10.1016/j.bioactmat.2026.01.001
Qiji Lu , Yudi Kuang , Jingjing Diao , Jiaqian Zheng , Naru Zhao , Chang Du , Yingjun Wang
{"title":"Geometry-driven immunomodulation in 3D-printed bioceramics: Negative curvature promotes macrophage M2 polarization via Ras-MAPK/HIF-1α signaling for vascularized osteogenesis","authors":"Qiji Lu ,&nbsp;Yudi Kuang ,&nbsp;Jingjing Diao ,&nbsp;Jiaqian Zheng ,&nbsp;Naru Zhao ,&nbsp;Chang Du ,&nbsp;Yingjun Wang","doi":"10.1016/j.bioactmat.2026.01.001","DOIUrl":"10.1016/j.bioactmat.2026.01.001","url":null,"abstract":"<div><div>The geometric features of bioactive scaffolds are biophysical cues regulate cell fate, but their immunomodulatory potential in bone regeneration is yet to be determined. Growing evidence suggests that surface curvature is a potent regulator of cellular behaviours and osteogenesis. Therefore, we quantitatively decoded this underlying mechanism by identifying Gaussian curvature(<em>K</em>) as a potent geometric regulator of macrophage polarization, creating a pro-regenerative microenvironment for bone repair. Using a high-throughput β-tricalcium phosphate(β-TCP) bioceramic platform (<em>K</em> = −4.91 to +4.82 mm<sup>−2</sup>), we demonstrate that negative gaussian curvature(<em>K</em><sup>−</sup>, <em>K</em>  &lt; −1.72 mm<sup>−2</sup>) promotes M2 macrophage polarization and endothelial CD31 expression. Mechanistically, single-cell <strong>transcriptomic</strong> RNA sequencing revealed that <em>K</em><sup><em>−</em></sup> scaffold downregulates hypoxia-inducible factor 1-alpha (HIF-1α) via Ras-mitogen-activated protein kinase (Ras-MAPK) inhibition and thus promotes macrophage M2 polarization, consequently elevating BMP2 and VEGF secretion. <em>In vivo</em>, β-TCP scaffolds with <em>K</em> = −1.72 mm<sup>−2</sup> achieved 42.4 % greater bone volume and higher torsional strength at 12 weeks than the scaffolds with <em>K</em> = +4.82 mm<sup>−2</sup> in 15 mm critical-sized segmental defects of rabbit radius. This work indicates a quantitative geometry-immunity relationship for bioceramic scaffolds, contributing to the development of topology-mediated immunomodulatory biomaterials.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 282-298"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075127","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}
引用次数: 0
Integrated fabrication of a shape-adaptable, antioxidative composite stent for effective closure and biological repair of enteroatmospheric fistula 一种形状适应性、抗氧化复合支架的集成制造,用于有效闭合和生物修复肠大气瘘
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-06-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bioactmat.2026.01.014
Guiwen Qu , Ze Li , Shuanghong Yang , Luqiao Huang , Ye Liu , Sicheng Li , Juanhan Liu , Lili Yu , Rui Ma , Yitian Teng , Haohui Li , Jinjian Huang , Jianan Ren , Xiuwen Wu
{"title":"Integrated fabrication of a shape-adaptable, antioxidative composite stent for effective closure and biological repair of enteroatmospheric fistula","authors":"Guiwen Qu ,&nbsp;Ze Li ,&nbsp;Shuanghong Yang ,&nbsp;Luqiao Huang ,&nbsp;Ye Liu ,&nbsp;Sicheng Li ,&nbsp;Juanhan Liu ,&nbsp;Lili Yu ,&nbsp;Rui Ma ,&nbsp;Yitian Teng ,&nbsp;Haohui Li ,&nbsp;Jinjian Huang ,&nbsp;Jianan Ren ,&nbsp;Xiuwen Wu","doi":"10.1016/j.bioactmat.2026.01.014","DOIUrl":"10.1016/j.bioactmat.2026.01.014","url":null,"abstract":"<div><div>Enteroatmospheric fistulas (EAFs) pose significant clinical challenges due to persistent leakage, inflammation, and impaired epithelial repair. Transcriptomic analyses of fistula tissues reveal elevated oxidative stress, mitochondrial dysfunction, and barrier disruption. Current provisional closure devices lack adaptability to complex fistula anatomy and fail to provide bioactive support, limiting tissue repair. Here, we report a body-temperature-responsive shape memory polymer stent coated with a bioactive hydrogel, fabricated through an integrated process, for effective EAF closure and repair. The stent can be delivered in a compact state and self-deployed <em>in vivo</em>, ensuring minimally invasive implantation and conformal closure. The composite stent enhances epithelial cell migration, attenuates oxidative stress, and alleviates inflammation, thereby establishing a microenvironment that promotes repair. In rabbit EAF models, the composite stent effectively closed the fistula, improved nutritional status, restored epithelial integrity, reduced inflammation, and enhanced goblet cell regeneration. Transcriptomic profiling and pathway validation revealed activation of oxidative phosphorylation, HIF-1, PI3K-Akt signaling, tight junction, and mucosal immune pathways, highlighting restoration of redox balance, mitochondrial metabolism, barrier integrity, and immune defense. These findings demonstrate that integrating dynamic shape adaptability with bioactive functionality can promote both physical closure and biological repair. This strategy provides a generalizable platform for treating complex epithelial defects in gastrointestinal organs.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 55-73"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036608","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}
引用次数: 0
Applications of micro/nano drug delivery systems in cancer pain management 微纳米给药系统在癌症疼痛治疗中的应用
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-06-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bioactmat.2026.01.013
Shizhen Geng , Yurou Zhang , Zhehao Zhang , Di Qiu , Panmiao Liu , Xueming Fan , Shiyong Song , Jinjin Shi , Jian-jun Yang
{"title":"Applications of micro/nano drug delivery systems in cancer pain management","authors":"Shizhen Geng ,&nbsp;Yurou Zhang ,&nbsp;Zhehao Zhang ,&nbsp;Di Qiu ,&nbsp;Panmiao Liu ,&nbsp;Xueming Fan ,&nbsp;Shiyong Song ,&nbsp;Jinjin Shi ,&nbsp;Jian-jun Yang","doi":"10.1016/j.bioactmat.2026.01.013","DOIUrl":"10.1016/j.bioactmat.2026.01.013","url":null,"abstract":"<div><div>Cancer pain, a critical complication associated with advanced malignant tumors, significantly diminishes patients’ quality of life and complicates therapeutic management due to its multifactorial pathophysiology. Current clinical analgesics often face limitations such as tolerance, addiction, and dose-dependent systemic toxicity. In contrast, micro/nano drug delivery systems (MNDDs) have emerged as promising strategies for managing cancer pain, owing to their unique advantages in precise targeting, including tumor-selective and neuropathic pain pathway targeting, controlled release, and multi-modal synergistic therapeutic effects. This review comprehensively examines the pathophysiological mechanisms underlying cancer pain, critically analyzes the pharmacological constraints and clinical limitations of existing analgesic regimens, and summarizes recent advances in engineered MNDDs. Additionally, we discuss the translational potential of multifunctional MNDDs, offering a multidisciplinary perspective to advance the development of precision-engineered, toxicity-minimized analgesic interventions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 128-162"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036676","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}
引用次数: 0
Age-related GSS promoter methylation in BMSCs drives osteoporosis and the reversal by targeted GSH delivery BMSCs中年龄相关的GSS启动子甲基化驱动骨质疏松症,并通过靶向GSH递送逆转
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-06-01 Epub Date: 2026-01-31 DOI: 10.1016/j.bioactmat.2025.12.048
Pan Li , Zhuowen Liang , Xianyan Zeng , Runbo Lei , Shuo Guo , Zhao Zhang , Guangwei Zhang , Jianxiong Li , Anhui Qin , Mi Qu , Kangkang Su , Dechen Yu , Wenwen Liu , Zhuojing Luo
{"title":"Age-related GSS promoter methylation in BMSCs drives osteoporosis and the reversal by targeted GSH delivery","authors":"Pan Li ,&nbsp;Zhuowen Liang ,&nbsp;Xianyan Zeng ,&nbsp;Runbo Lei ,&nbsp;Shuo Guo ,&nbsp;Zhao Zhang ,&nbsp;Guangwei Zhang ,&nbsp;Jianxiong Li ,&nbsp;Anhui Qin ,&nbsp;Mi Qu ,&nbsp;Kangkang Su ,&nbsp;Dechen Yu ,&nbsp;Wenwen Liu ,&nbsp;Zhuojing Luo","doi":"10.1016/j.bioactmat.2025.12.048","DOIUrl":"10.1016/j.bioactmat.2025.12.048","url":null,"abstract":"<div><div>Age-related osteoporosis arises from bone tissue with inadequate metabolic support for osteogenesis. We identified that DNA methylation-mediated suppression of glutathione synthetase (GSS) represents an upstream lesion limiting endogenous glutathione (GSH) synthesis and supply in aged bone, thereby constraining osteoblast differentiation. In turn, impaired GSH synthesis exacerbates oxidative stress levels and diminishes osteogenic capacity, and this metabolic bottleneck is independent of substrate availability: cysteine supplementation neither restored GSH synthesis flux in aged bone nor rescued its osteogenic deficits. To overcome this limitation, we developed an exosome-based GSH delivery platform using electroporation to efficiently load GSH. These exosomes are derived from CXCR4-enriched bone marrow mesenchymal stem cells (BMSCs), leveraging CXCR4-mediated homing to the bone marrow niche to enhance bone retention, stabilize GSH during loading and circulation, and elevate local GSH pools at osteogenic sites. In aged bone, this targeted system sustainably delivers GSH, alleviates oxidative stress, improves mitochondrial function, delays cellular senescence, and promotes osteogenesis. In summary, while DNA methylation acts upstream to constrain GSH synthesis in aging bone, therapeutically correcting the resultant metabolic deficit via bone-homing exosome–mediated GSH delivery restores osteogenic function and improves bone metabolism in aged individuals.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 472-491"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075129","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}
引用次数: 0
Bioactive-coated porous anastomotic staples enhance anastomotic healing 生物活性涂层多孔吻合器促进吻合口愈合
IF 18 1区 医学
Bioactive Materials Pub Date : 2026-06-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bioactmat.2026.01.005
Renjie Li , Qi Sun , Ruijun Xu , Runlong Zhu , Jiarui Lin , Qijing Tang , Qihuan Zhou , Yong Li , Feng Wang , Zifeng Yang
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