Pub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.actbio.2026.01.009
Yoshikazu Kameda , Kazuya Fujimoto , Miki Yoshioka , Tatsuji Enoki , Jun K. Yamashita , Ryuji Yokokawa
This study aimed to identify the key determinants of vascular networks (VN) morphology, with a particular focus on the role of endothelial cell body area expansion. We introduced a quantitative metric, the cell body area expansion (CBE) score, to assess endothelial cell (EC) enlargement during the early stage of self-organizing vascular network formation. The CBE score positively correlated with both VN connectivity and vessel diameter. Notably, VNs formed in the absence of growth factors exhibited reduced connectivity accompanied by lower CBE scores, while protrusion formation remained unaffected. Additionally, comparative analysis of multiple EC types revealed that cells forming wider vascular branches consistently showed higher CBE score. A mathematical model further supported these findings, demonstrating that greater CBE leads to VNs with enhanced connectivity and larger branch diameters.
Statement of Significance
The on-chip vascular network, a luminal network structure formed by endothelial cells within a microfluidic device, has attracted significant attention as a promising platform for vascular disease modeling and coculture with spheroids and organoids. However, the complexity of the vascular formation process poses challenges in optimizing network formation. This study identifies cell body expansion (CBE) as a key determinant of vascular network morphology through time lapse observations and image analysis of the formation process. Furthermore, mathematical modelling provided consistent supporting results. These findings provide valuable insights into vascular network formation and serve as a framework for designing vascular networks with desired connectivity and diameter.
{"title":"Cell body area expansion is a key factor determining connectivity and diameter of on-chip vascular networks","authors":"Yoshikazu Kameda , Kazuya Fujimoto , Miki Yoshioka , Tatsuji Enoki , Jun K. Yamashita , Ryuji Yokokawa","doi":"10.1016/j.actbio.2026.01.009","DOIUrl":"10.1016/j.actbio.2026.01.009","url":null,"abstract":"<div><div>This study aimed to identify the key determinants of vascular networks (VN) morphology, with a particular focus on the role of endothelial cell body area expansion. We introduced a quantitative metric, the cell body area expansion (CBE) score, to assess endothelial cell (EC) enlargement during the early stage of self-organizing vascular network formation. The CBE score positively correlated with both VN connectivity and vessel diameter. Notably, VNs formed in the absence of growth factors exhibited reduced connectivity accompanied by lower CBE scores, while protrusion formation remained unaffected. Additionally, comparative analysis of multiple EC types revealed that cells forming wider vascular branches consistently showed higher CBE score. A mathematical model further supported these findings, demonstrating that greater CBE leads to VNs with enhanced connectivity and larger branch diameters.</div></div><div><h3>Statement of Significance</h3><div>The on-chip vascular network, a luminal network structure formed by endothelial cells within a microfluidic device, has attracted significant attention as a promising platform for vascular disease modeling and coculture with spheroids and organoids. However, the complexity of the vascular formation process poses challenges in optimizing network formation. This study identifies cell body expansion (CBE) as a key determinant of vascular network morphology through time lapse observations and image analysis of the formation process. Furthermore, mathematical modelling provided consistent supporting results. These findings provide valuable insights into vascular network formation and serve as a framework for designing vascular networks with desired connectivity and diameter.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 444-458"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949380","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}
<div><div>A comprehensive understanding of skeletal muscle mechanics requires models that reflect its hierarchical structure and biophysical complexity. This study presents a multiscale continuum model grounded in sarcomere-level mechanisms and extending to the whole-muscle fiber scale under uniaxial loading conditions. Key structural components - including aligned myofibrils, helically oriented collagen fibers, and isotropic matrices such as the proteoglycan-rich extracellular matrix and muscle fiber membrane - are embedded in a composite framework that separates and integrates anisotropic and isotropic mechanical contributions. Based on a network decomposition strategy, myofibrils are divided into actin-myosin weak bindings and titin filaments, each modeled as a distinct macromolecular network. A network alteration framework models both subsystems as dynamic internal variables, with stiffness evolving through stretch-dependent recruitment and rate-sensitive kinetics. A non-affine deformation concept captures the asynchronous engagement of sarcomeric elements, providing a microstructural basis for delayed stiffness development. Though primarily focused on the uniaxial passive response, the model includes a minimal active term to explore how activation modulates stiffness through shared structural pathways. The formulation reproduces key passive features - including nonlinear stiffening, rate sensitivity, and relaxation - using time-dependent internal variables and microstructural recruitment. The model reproduces experimental data from human and animal muscle fibers across various loading protocols, showing strong agreement at both fiber and tissue scales. By linking molecular processes to macroscopic mechanics without relying on phenomenological viscoelastic terms, the model offers a computationally efficient and physiologically grounded tool for exploring skeletal muscle behavior under normal and altered conditions.</div></div><div><h3>Statement of significance</h3><div>Accurately modeling skeletal muscle mechanics remains a major challenge due to the tissue structural complexity, time-dependent behavior, and scale-bridging physiological processes. This study introduces a multiscale continuum model that integrates sarcomere-level macromolecular mechanisms - namely titin unfolding/refolding, passive actin-myosin interactions, and non-affine filament engagement - into a computationally tractable tissue-scale formulation. By combining statistical mechanics-based representations of filament networks with dynamic internal variables, the model captures key experimental phenomena such as stress relaxation, strain-rate sensitivity, and nonlinear stiffening without relying on phenomenological viscoelastic laws. The approach is broadly applicable to musculoskeletal modeling and provides a biophysically interpretable framework for simulating healthy and diseased muscle, with direct relevance for tissue engineering, rehabilitation, and the study of degene
{"title":"A multiscale sarcomere-to-fiber modeling approach for time-dependent uniaxial skeletal muscle mechanics","authors":"Maxime Hoyaux , Abderrahman Tamoud , Tang Gu , Fahmi Zaïri , Fahed Zaïri","doi":"10.1016/j.actbio.2026.01.010","DOIUrl":"10.1016/j.actbio.2026.01.010","url":null,"abstract":"<div><div>A comprehensive understanding of skeletal muscle mechanics requires models that reflect its hierarchical structure and biophysical complexity. This study presents a multiscale continuum model grounded in sarcomere-level mechanisms and extending to the whole-muscle fiber scale under uniaxial loading conditions. Key structural components - including aligned myofibrils, helically oriented collagen fibers, and isotropic matrices such as the proteoglycan-rich extracellular matrix and muscle fiber membrane - are embedded in a composite framework that separates and integrates anisotropic and isotropic mechanical contributions. Based on a network decomposition strategy, myofibrils are divided into actin-myosin weak bindings and titin filaments, each modeled as a distinct macromolecular network. A network alteration framework models both subsystems as dynamic internal variables, with stiffness evolving through stretch-dependent recruitment and rate-sensitive kinetics. A non-affine deformation concept captures the asynchronous engagement of sarcomeric elements, providing a microstructural basis for delayed stiffness development. Though primarily focused on the uniaxial passive response, the model includes a minimal active term to explore how activation modulates stiffness through shared structural pathways. The formulation reproduces key passive features - including nonlinear stiffening, rate sensitivity, and relaxation - using time-dependent internal variables and microstructural recruitment. The model reproduces experimental data from human and animal muscle fibers across various loading protocols, showing strong agreement at both fiber and tissue scales. By linking molecular processes to macroscopic mechanics without relying on phenomenological viscoelastic terms, the model offers a computationally efficient and physiologically grounded tool for exploring skeletal muscle behavior under normal and altered conditions.</div></div><div><h3>Statement of significance</h3><div>Accurately modeling skeletal muscle mechanics remains a major challenge due to the tissue structural complexity, time-dependent behavior, and scale-bridging physiological processes. This study introduces a multiscale continuum model that integrates sarcomere-level macromolecular mechanisms - namely titin unfolding/refolding, passive actin-myosin interactions, and non-affine filament engagement - into a computationally tractable tissue-scale formulation. By combining statistical mechanics-based representations of filament networks with dynamic internal variables, the model captures key experimental phenomena such as stress relaxation, strain-rate sensitivity, and nonlinear stiffening without relying on phenomenological viscoelastic laws. The approach is broadly applicable to musculoskeletal modeling and provides a biophysically interpretable framework for simulating healthy and diseased muscle, with direct relevance for tissue engineering, rehabilitation, and the study of degene","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 496-515"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949239","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}
Pub Date : 2026-03-01Epub Date: 2025-12-10DOI: 10.1016/j.actbio.2025.12.021
Dong Xie , Manxiang Wu , Lianfu Wang , Pingting Luo , Xinxin Wei , Tao Ye , Yi Liu , Tianxiang Chen , Aiguo Wu , Qiang Li
Photothermal therapy (PTT) is a promising strategy for cancer treatment, yet traditional high-temperature PTT (>50 °C) often induces heat shock protein (HSP) overexpression and exacerbates tumor hypoxia, particularly in triple-negative breast cancer (TNBC), thereby promoting therapeutic resistance and limiting efficacy. In contrast, mild PTT (<45 °C) has gained increasing attention for its ability to exert therapeutic effects while minimizing damage to surrounding normal tissues. Herein, we developed a biomimetic nanoplatform, tFBSG@M BNPs, to enhance mild PTT through a cascade-amplified synergistic mechanism tailored to the TNBC microenvironment. By coating iron-doped bismuth sulfide nanoparticles with tumor cell membranes for homologous targeting, this nanoplatform integrates three interconnected therapeutic actions: (1) Mild PTT, alleviates hypoxia by improving local blood flow and oxygen supply, both reducing HSP-mediated thermotolerance and preparing the tumor microenvironment for downstream catalysis. (2) Higher oxygen levels boost GOx-mediated starvation therapy, depleting glucose and generating H2O2, which not only disrupts tumor metabolism but also serves as a substrate for further oxidative amplification. (3) H2O2 is catalytically converted by Fe2+ centers into •OH via a Fenton reaction, unleashing potent oxidative stress that completes the self-amplifying cascade and drives apoptosis. This cascade-driven approach achieved a 96.52 % tumor volume reduction under NIR irradiation. MRI showed a 190 % increase in T1 signal at the tumor site, confirming nanoparticle accumulation; CT provided a 24.7 HU contrast enhancement for clear boundary mapping; and PA imaging visualized tumor vasculature and blood oxygen saturation. By uniting mild PTT, metabolic disruption, and ROS amplification in a single tumor-targeted platform, tFBSG@M BNPs offer a promising strategy to overcome TNBC resistance and improve therapeutic outcomes.
Statement of significance
1. A cascade-amplified therapeutic mechanism that overcomes TNBC’s hypoxia, HSP-mediated thermotolerance, and antioxidant defenses through the integration of mild photothermal therapy, GOx-mediated starvation, and Fenton reaction–driven chemodynamic therapy. 2. A multifunctional nanoplatform (tFBSG@M BNPs) that combines iron-doped Bi2S3, glucose oxidase, and homologous tumor membranes, achieving 96.52 % tumor suppression and a 7.4-fold increase in ROS under mild PTT in an orthotopic TNBC model. 3. A clinically adaptable multimodal imaging strategy, combining CT, MRI, and PA imaging in a stepwise fashion to guide therapy with precise boundary mapping, soft tissue resolution, and vascular visualization.
{"title":"Cascade-amplified iron-doped bismuth sulfide biomimetic nanoplatform for synergistic therapy and multimodal imaging of triple-negative breast cancer","authors":"Dong Xie , Manxiang Wu , Lianfu Wang , Pingting Luo , Xinxin Wei , Tao Ye , Yi Liu , Tianxiang Chen , Aiguo Wu , Qiang Li","doi":"10.1016/j.actbio.2025.12.021","DOIUrl":"10.1016/j.actbio.2025.12.021","url":null,"abstract":"<div><div>Photothermal therapy (PTT) is a promising strategy for cancer treatment, yet traditional high-temperature PTT (>50 °C) often induces heat shock protein (HSP) overexpression and exacerbates tumor hypoxia, particularly in triple-negative breast cancer (TNBC), thereby promoting therapeutic resistance and limiting efficacy. In contrast, mild PTT (<45 °C) has gained increasing attention for its ability to exert therapeutic effects while minimizing damage to surrounding normal tissues. Herein, we developed a biomimetic nanoplatform, tFBSG@M BNPs, to enhance mild PTT through a cascade-amplified synergistic mechanism tailored to the TNBC microenvironment. By coating iron-doped bismuth sulfide nanoparticles with tumor cell membranes for homologous targeting, this nanoplatform integrates three interconnected therapeutic actions: (1) Mild PTT, alleviates hypoxia by improving local blood flow and oxygen supply, both reducing HSP-mediated thermotolerance and preparing the tumor microenvironment for downstream catalysis. (2) Higher oxygen levels boost GOx-mediated starvation therapy, depleting glucose and generating H<sub>2</sub>O<sub>2</sub>, which not only disrupts tumor metabolism but also serves as a substrate for further oxidative amplification. (3) H<sub>2</sub>O<sub>2</sub> is catalytically converted by Fe<sup>2+</sup> centers into •OH via a Fenton reaction, unleashing potent oxidative stress that completes the self-amplifying cascade and drives apoptosis. This cascade-driven approach achieved a 96.52 % tumor volume reduction under NIR irradiation. MRI showed a 190 % increase in T1 signal at the tumor site, confirming nanoparticle accumulation; CT provided a 24.7 HU contrast enhancement for clear boundary mapping; and PA imaging visualized tumor vasculature and blood oxygen saturation. By uniting mild PTT, metabolic disruption, and ROS amplification in a single tumor-targeted platform, tFBSG@M BNPs offer a promising strategy to overcome TNBC resistance and improve therapeutic outcomes.</div></div><div><h3>Statement of significance</h3><div>1. A cascade-amplified therapeutic mechanism that overcomes TNBC’s hypoxia, HSP-mediated thermotolerance, and antioxidant defenses through the integration of mild photothermal therapy, GOx-mediated starvation, and Fenton reaction–driven chemodynamic therapy. 2. A multifunctional nanoplatform (tFBSG@M BNPs) that combines iron-doped Bi<sub>2</sub>S<sub>3</sub>, glucose oxidase, and homologous tumor membranes, achieving 96.52 % tumor suppression and a 7.4-fold increase in ROS under mild PTT in an orthotopic TNBC model. 3. A clinically adaptable multimodal imaging strategy, combining CT, MRI, and PA imaging in a stepwise fashion to guide therapy with precise boundary mapping, soft tissue resolution, and vascular visualization.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 816-828"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746091","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}
Pub Date : 2026-03-01Epub Date: 2025-12-25DOI: 10.1016/j.actbio.2025.12.046
Jianqin Yan , Fei Sun , Min Wang , Xianwen Wang
Reactive oxygen species (ROS) play critical roles in both physiological and pathological processes. However, excessive accumulation of ROS induces oxidative stress, leading to cellular damage and promoting the progression of inflammatory responses, ultimately resulting in various inflammatory diseases. Traditional antioxidants are limited by poor bioavailability, rapid metabolism, and potential side effects. Nanoantioxidants, which combine the advantages of nanotechnology and antioxidant properties, exhibit superior ROS-scavenging capabilities and improved drug delivery efficiency. This review first introduces the biological effects of ROS and highlights their pivotal role in regulating inflammatory signaling pathways, thereby highlighting the underlying mechanisms by which nanoantioxidants modulate inflammation through ROS elimination. This article focuses on the design strategies of various types of nanoantioxidants, including nanozyme-based systems, bioderived materials, and nanomaterials incorporating ROS-responsive moieties. Furthermore, the therapeutic applications of these nanoantioxidants in both acute and chronic inflammatory conditions are discussed in detail. Finally, the review summarizes current challenges in the clinical translation of nanoantioxidants and outlines future research directions aimed at meeting the complex therapeutic needs of inflammation management.
Statement of significance
Reactive oxygen species (ROS) play critical roles in both physiological and pathological processes. However, overaccumulation of ROS induces oxidative stress, leading to cellular damage and exacerbated inflammation. Nanoantioxidants merge nanotechnology with antioxidant properties, enhancing both ROS scavenging and drug delivery.This review examines the roles of ROS in inflammatory signaling, highlighting the mechanisms through which nanoantioxidants modulate inflammation via ROS elimination. It systematically outlines the design strategies of various nanoantioxidants, focusing on nanozyme-based systems, bioderived materials, and nanomaterials incorporating ROS-responsive components. The therapeutic applications of nanoantioxidants in acute and chronic inflammatory conditions are discussed. Finally, the review summarizes the challenges in clinical translation and future research directions of nanoantioxidants to meet the complex therapeutic demands of inflammation.
{"title":"Reactive oxygen species-scavenging nanoantioxidants in inflammation: Design and therapy","authors":"Jianqin Yan , Fei Sun , Min Wang , Xianwen Wang","doi":"10.1016/j.actbio.2025.12.046","DOIUrl":"10.1016/j.actbio.2025.12.046","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) play critical roles in both physiological and pathological processes. However, excessive accumulation of ROS induces oxidative stress, leading to cellular damage and promoting the progression of inflammatory responses, ultimately resulting in various inflammatory diseases. Traditional antioxidants are limited by poor bioavailability, rapid metabolism, and potential side effects. Nanoantioxidants, which combine the advantages of nanotechnology and antioxidant properties, exhibit superior ROS-scavenging capabilities and improved drug delivery efficiency. This review first introduces the biological effects of ROS and highlights their pivotal role in regulating inflammatory signaling pathways, thereby highlighting the underlying mechanisms by which nanoantioxidants modulate inflammation through ROS elimination. This article focuses on the design strategies of various types of nanoantioxidants, including nanozyme-based systems, bioderived materials, and nanomaterials incorporating ROS-responsive moieties. Furthermore, the therapeutic applications of these nanoantioxidants in both acute and chronic inflammatory conditions are discussed in detail. Finally, the review summarizes current challenges in the clinical translation of nanoantioxidants and outlines future research directions aimed at meeting the complex therapeutic needs of inflammation management.</div></div><div><h3>Statement of significance</h3><div>Reactive oxygen species (ROS) play critical roles in both physiological and pathological processes. However, overaccumulation of ROS induces oxidative stress, leading to cellular damage and exacerbated inflammation. Nanoantioxidants merge nanotechnology with antioxidant properties, enhancing both ROS scavenging and drug delivery.This review examines the roles of ROS in inflammatory signaling, highlighting the mechanisms through which nanoantioxidants modulate inflammation via ROS elimination. It systematically outlines the design strategies of various nanoantioxidants, focusing on nanozyme-based systems, bioderived materials, and nanomaterials incorporating ROS-responsive components. The therapeutic applications of nanoantioxidants in acute and chronic inflammatory conditions are discussed. Finally, the review summarizes the challenges in clinical translation and future research directions of nanoantioxidants to meet the complex therapeutic demands of inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 18-41"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847040","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}
Pub Date : 2026-03-01Epub Date: 2026-01-02DOI: 10.1016/j.actbio.2025.12.044
Wenhao Pan , Dongyu Li , Liujing Pan , Chunli Wang , Min Li , Zai-Sheng Wu
Cancer poses a crucial risk to human health because of its complexity and heterogeneity. Precision medicine has been widely noticed as an emerging concept, which brings great opportunities to improve cancer diagnosis and treatment. Here, tumor biomarkers and corresponding diseased-site targeting strategies are emphasized, recognition ligands with high specificity and affinity are summarized and the common and creative approaches of precision medicine are discussed. Further, precision targeting systems (PTS) based on different numbers of tumor biomarkers, including single-, dual- and triple biomarker-based PTS, are reviewed. Based on the binding of multiple recognition probes to different markers especially in a sequential manner, the advantages of synergistic targeting strategies in cancer diagnosis and treatment are separately highlighted. In addition, the application of single- and multi-marker-based PTS in detecting the expression level of specific molecules, inducing the dysfunctional species within subcellular locations (e.g., nucleus and mitochondria) is summarized. Finally, the challenges and future perspective of PTS based on multiple biomarkers are discussed. The review indicates that further improvement of precision medicine relies on new breakthroughs in the discovery of biomarkers exclusive to diseased cells and their ingenious combination, which will become a cornerstone of biomedical studies and clinical precision medicine.
Statement of significance
To a large degree, significant advancement in precision medicine is highly dependent on the development of precision targeting systems (PTS) based on the recognition of multi-ligands to different targets, coupled with a deep understanding of their operational mechanisms for tumor cell recognition and drug delivery. This review summarizes common tumor biomarker receptors and their specific recognition ligands, the design of targeted delivery systems based on single or multiple tumor biomarkers (especially sequential targeting systems), the molecular mechanisms for their operation, and their applications within subcellular structures. These innovations deepen our understanding of the design and operational mechanisms of PTS and reveal their potential to overcome tumor heterogeneity. By emphasizing the unique advantages of precision targeting systems, this review is expected to efficiently highlight the precision medicine of cancer patients and offered a new opportunity for cancer prevention, treatment, and prognosis in a precise manner.
{"title":"Synergistic targeting systems for cancer precision medicine: co- and sequential binding to multiple tumor biomarkers","authors":"Wenhao Pan , Dongyu Li , Liujing Pan , Chunli Wang , Min Li , Zai-Sheng Wu","doi":"10.1016/j.actbio.2025.12.044","DOIUrl":"10.1016/j.actbio.2025.12.044","url":null,"abstract":"<div><div>Cancer poses a crucial risk to human health because of its complexity and heterogeneity. Precision medicine has been widely noticed as an emerging concept, which brings great opportunities to improve cancer diagnosis and treatment. Here, tumor biomarkers and corresponding diseased-site targeting strategies are emphasized, recognition ligands with high specificity and affinity are summarized and the common and creative approaches of precision medicine are discussed. Further, precision targeting systems (PTS) based on different numbers of tumor biomarkers, including single-, dual- and triple biomarker-based PTS, are reviewed. Based on the binding of multiple recognition probes to different markers especially in a sequential manner, the advantages of synergistic targeting strategies in cancer diagnosis and treatment are separately highlighted. In addition, the application of single- and multi-marker-based PTS in detecting the expression level of specific molecules, inducing the dysfunctional species within subcellular locations (e.g., nucleus and mitochondria) is summarized. Finally, the challenges and future perspective of PTS based on multiple biomarkers are discussed. The review indicates that further improvement of precision medicine relies on new breakthroughs in the discovery of biomarkers exclusive to diseased cells and their ingenious combination, which will become a cornerstone of biomedical studies and clinical precision medicine.</div></div><div><h3>Statement of significance</h3><div>To a large degree, significant advancement in precision medicine is highly dependent on the development of precision targeting systems (PTS) based on the recognition of multi-ligands to different targets, coupled with a deep understanding of their operational mechanisms for tumor cell recognition and drug delivery. This review summarizes common tumor biomarker receptors and their specific recognition ligands, the design of targeted delivery systems based on single or multiple tumor biomarkers (especially sequential targeting systems), the molecular mechanisms for their operation, and their applications within subcellular structures. These innovations deepen our understanding of the design and operational mechanisms of PTS and reveal their potential to overcome tumor heterogeneity. By emphasizing the unique advantages of precision targeting systems, this review is expected to efficiently highlight the precision medicine of cancer patients and offered a new opportunity for cancer prevention, treatment, and prognosis in a precise manner.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 67-102"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901827","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}
Pub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.actbio.2025.12.037
Chi Zhang , Yiqiang Li , Yibo Zhang , Jian Xue , Xiaohui Lin , Yanchao Li , Dongxu Wang , Jinlong Liu , Gaosen Zhang , Haoyang Jiang , Meng Niu , Yang Chu , Hongwei Zhao
{"title":"Corrigendum to “The Mo-14Re alloy, a promising candidate material for bioresorbable vascular scaffolds” [Acta Biomaterialia 204, 2025, 657-673]","authors":"Chi Zhang , Yiqiang Li , Yibo Zhang , Jian Xue , Xiaohui Lin , Yanchao Li , Dongxu Wang , Jinlong Liu , Gaosen Zhang , Haoyang Jiang , Meng Niu , Yang Chu , Hongwei Zhao","doi":"10.1016/j.actbio.2025.12.037","DOIUrl":"10.1016/j.actbio.2025.12.037","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 868-869"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947130","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}
Pub Date : 2026-03-01Epub Date: 2026-01-13DOI: 10.1016/j.actbio.2026.01.021
Ying Li , Yiting Yin , Duo Li , Bin Gao , Yuanchao Wang , Xiangyan Meng , Yakai Feng
Blast accidents are common in daily life and industrial settings and frequently result in acute lung injury (ALI), which may progress to respiratory failure in severe cases. Beyond the initial mechanical insult, dysregulated inflammatory responses and excessive reactive oxygen species (ROS) generation drive sustained ALI progression. However, current therapeutic strategies are limited by suboptimal efficacy and systemic side effects, highlighting an urgent need for more effective interventions. Herein, we develop a self-immolative, ROS-responsive nanoplatform (PPTCBR) for multi-targeted therapeutic intervention against blast-induced ALI. The nanoplatform is constructed from poly(ethylene glycol)-modified poly(L-lysine) incorporating ROS-cleavable thiocarbamate moieties. Under pathological high-ROS conditions, PPTCBR nanoparticles undergo self-immolative degradation, releasing carbonyl sulfide (COS), which is subsequently converted by endogenous carbonic anhydrase into hydrogen sulfide (H₂S) with potent anti-inflammatory and antioxidant activities. Concurrently, the resulting cationic polymer framework neutralizes cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), thereby interrupting inflammatory cascade amplification. Moreover, surface modification with RGD peptides enhances active targeting and retention in injured lung tissue. Systematic in vitro and in vivo studies demonstrate that PPTCBR nanoparticles exhibit excellent ROS responsiveness, favorable biocompatibility, and effective pulmonary accumulation, significantly alleviating blast-induced ALI and improving lung function. These findings present a pathology-responsive and multi-target nanotherapeutic strategy integrating immunomodulation for effective blast-induced ALI management.
Statement of significance
1. This work developed targeted ROS-responsive self-immolative nanoparticles to intelligently deliver H₂S for regulating the inflammatory microenvironment. 2. The nanoparticles enabled binding of cfDNA/NETs in situ at the site of inflammation after degradation. 3. The nanoparticles exhibited excellent therapeutic effects in blast induced ALI mice models. 4. The proposed multifunctional nanoparticles are a promising therapeutic strategy for inflammatory diseases.
{"title":"Multi-targeted ROS-responsive self-immolative nanoparticles for releasing hydrogen sulfide and in situ binding of Cell-Free DNA in blast-induced acute lung injury","authors":"Ying Li , Yiting Yin , Duo Li , Bin Gao , Yuanchao Wang , Xiangyan Meng , Yakai Feng","doi":"10.1016/j.actbio.2026.01.021","DOIUrl":"10.1016/j.actbio.2026.01.021","url":null,"abstract":"<div><div>Blast accidents are common in daily life and industrial settings and frequently result in acute lung injury (ALI), which may progress to respiratory failure in severe cases. Beyond the initial mechanical insult, dysregulated inflammatory responses and excessive reactive oxygen species (ROS) generation drive sustained ALI progression. However, current therapeutic strategies are limited by suboptimal efficacy and systemic side effects, highlighting an urgent need for more effective interventions. Herein, we develop a self-immolative, ROS-responsive nanoplatform (PPTCBR) for multi-targeted therapeutic intervention against blast-induced ALI. The nanoplatform is constructed from poly(ethylene glycol)-modified poly(L-lysine) incorporating ROS-cleavable thiocarbamate moieties. Under pathological high-ROS conditions, PPTCBR nanoparticles undergo self-immolative degradation, releasing carbonyl sulfide (COS), which is subsequently converted by endogenous carbonic anhydrase into hydrogen sulfide (H₂S) with potent anti-inflammatory and antioxidant activities. Concurrently, the resulting cationic polymer framework neutralizes cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), thereby interrupting inflammatory cascade amplification. Moreover, surface modification with RGD peptides enhances active targeting and retention in injured lung tissue. Systematic in vitro and in vivo studies demonstrate that PPTCBR nanoparticles exhibit excellent ROS responsiveness, favorable biocompatibility, and effective pulmonary accumulation, significantly alleviating blast-induced ALI and improving lung function. These findings present a pathology-responsive and multi-target nanotherapeutic strategy integrating immunomodulation for effective blast-induced ALI management.</div></div><div><h3>Statement of significance</h3><div>1. This work developed targeted ROS-responsive self-immolative nanoparticles to intelligently deliver H₂S for regulating the inflammatory microenvironment. 2. The nanoparticles enabled binding of cfDNA/NETs in situ at the site of inflammation after degradation. 3. The nanoparticles exhibited excellent therapeutic effects in blast induced ALI mice models. 4. The proposed multifunctional nanoparticles are a promising therapeutic strategy for inflammatory diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 802-815"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985673","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}
Pub Date : 2026-03-01Epub Date: 2026-01-16DOI: 10.1016/j.actbio.2026.01.032
Aodi Jiang , Ya Ma , Shengfei Bao , Mohammad-Ali Shahbazi , Rui L. Reis , Subhas C. Kundu , Bo Xiao , Xiaoxiao Shi
Metal-directed self-assembly, driven by metal-ligand coordination, represents a highly versatile and efficient strategy for constructing drug delivery systems with precisely tunable properties, inherent imaging capabilities, and broad biomedical applications. Stimuli-responsive metal-directed drug delivery systems (MDDSs), guided by advanced imaging techniques, enable precise control over their size and spatial architecture while facilitating site-specific drug release. Moreover, certain metal ions play a dual role, not only orchestrating the self-assembly process but also serving as therapeutic agents and regulatory components for the treatment of various diseases, including cancer, microbial infections, and Alzheimer’s disease. This review provides a comprehensive overview of the self-assembly mechanisms underlying diverse MDDSs and their applications in image-guided therapy. Furthermore, we critically examine existing challenges in the field and propose strategic directions to propel the advancement of metal-directed self-assembly in drug delivery. Given the profound implications of this research, further exploration of the critical roles of metal coordination in self-assembly is imperative for the development of next-generation drug delivery platforms.
Statement of significance
This review systematically summarize the self-assembly mechanisms of metal-directed drug delivery systems, outlines their applications in image-guided therapy and discusses the current challenges that remain. Furthermore, it elucidates the unique regulatory roles of metal ions in precise drug release and multimodal therapy, providing valuable insights and broad appeal for the development and clinical translation of next-generation smart nanomedicine platforms.
{"title":"Metal-directed nanomedicines for imaging-guided disease treatment","authors":"Aodi Jiang , Ya Ma , Shengfei Bao , Mohammad-Ali Shahbazi , Rui L. Reis , Subhas C. Kundu , Bo Xiao , Xiaoxiao Shi","doi":"10.1016/j.actbio.2026.01.032","DOIUrl":"10.1016/j.actbio.2026.01.032","url":null,"abstract":"<div><div>Metal-directed self-assembly, driven by metal-ligand coordination, represents a highly versatile and efficient strategy for constructing drug delivery systems with precisely tunable properties, inherent imaging capabilities, and broad biomedical applications. Stimuli-responsive metal-directed drug delivery systems (MDDSs), guided by advanced imaging techniques, enable precise control over their size and spatial architecture while facilitating site-specific drug release. Moreover, certain metal ions play a dual role, not only orchestrating the self-assembly process but also serving as therapeutic agents and regulatory components for the treatment of various diseases, including cancer, microbial infections, and Alzheimer’s disease. This review provides a comprehensive overview of the self-assembly mechanisms underlying diverse MDDSs and their applications in image-guided therapy. Furthermore, we critically examine existing challenges in the field and propose strategic directions to propel the advancement of metal-directed self-assembly in drug delivery. Given the profound implications of this research, further exploration of the critical roles of metal coordination in self-assembly is imperative for the development of next-generation drug delivery platforms.</div></div><div><h3>Statement of significance</h3><div>This review systematically summarize the self-assembly mechanisms of metal-directed drug delivery systems, outlines their applications in image-guided therapy and discusses the current challenges that remain. Furthermore, it elucidates the unique regulatory roles of metal ions in precise drug release and multimodal therapy, providing valuable insights and broad appeal for the development and clinical translation of next-generation smart nanomedicine platforms.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 42-66"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999907","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}
Pub Date : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.actbio.2026.01.037
Yuchen Zhang , Yucheng Luo , Yuang Song, Haonan Xing, Ye Li, Bin Li, Feng Lu, Ziqing Dong
Reconstruction of large-volume soft tissue defects remains a significant challenge in plastic and reconstructive surgery. Autologous fat grafting, though widely used, often suffers from poor volume retention and slow vascularization. This study presents an innovative collagen-guided self-assembling adipose construct from clinical lipoaspirate to create structurally stable engineered fat flaps—Self-Assembly Fat (SAF), driven by the intrinsic crosslinking of type I collagen within the lipoaspirated fat. Supplementation with exogenous type I collagen (SAF⁺) further enhanced the mechanical properties and biological activity of these constructs, increasing their stiffness, elasticity, and resilience. The self-assembly process facilitated collagen network formation, which not only improved tissue stability but also provided a favorable microenvironment for cell adhesion, proliferation, and differentiation. In vitro, SAF⁺ exhibited enhanced adipogenic differentiation and superior stem cell recruitment. In vivo, SAF⁺ significantly accelerated tissue repair by promoting M2 macrophage polarization, angiogenesis, and stem cell homing. Mechanistically, these effects were mediated through activation of the integrin α2β1–FAK/Src signaling pathway. This study provides a mechanistic understanding of adipose tissue self-assembly and presents an autologous, collagen-guided approach for engineering implantable, scaffold-free adipose constructs with enhanced regenerative capacity for soft-tissue repair.
Statement of significance
Soft‑tissue reconstruction is hindered by unpredictable resorption and poor vascularization of autologous fat grafts. Biomaterial approaches using synthetic scaffolds or exogenous matrices often suffer biocompatibility issues, foreign‑body responses, and limited integration. We identify an intrinsic, type I collagen–driven self‑assembly capacity in human lipoaspirate and establish a collagen-guided, scaffold-free adipose strategy. By elucidating collagen signaling via integrin α2β1–FAK/Src axis, we link structural consolidation, mechanical tuning, and a pro‑regenerative microenvironment. Modulating collagen availability and crosslinking strengthens cohesion while preserving implantability and handling. The resulting constructs maintain adipose lineage, support vascularization, and integrate with host tissue. Bypassing synthetic scaffolds, this platform advances ECM‑guided assembly and offers a practical, autologous approach to soft‑tissue repair with improved handling, stability, and translational potential.
{"title":"A scaffold-free, collagen-guided self-assembling adipose construct for functional soft tissue reconstruction","authors":"Yuchen Zhang , Yucheng Luo , Yuang Song, Haonan Xing, Ye Li, Bin Li, Feng Lu, Ziqing Dong","doi":"10.1016/j.actbio.2026.01.037","DOIUrl":"10.1016/j.actbio.2026.01.037","url":null,"abstract":"<div><div>Reconstruction of large-volume soft tissue defects remains a significant challenge in plastic and reconstructive surgery. Autologous fat grafting, though widely used, often suffers from poor volume retention and slow vascularization. This study presents an innovative collagen-guided self-assembling adipose construct from clinical lipoaspirate to create structurally stable engineered fat flaps—Self-Assembly Fat (SAF), driven by the intrinsic crosslinking of type I collagen within the lipoaspirated fat. Supplementation with exogenous type I collagen (SAF⁺) further enhanced the mechanical properties and biological activity of these constructs, increasing their stiffness, elasticity, and resilience. The self-assembly process facilitated collagen network formation, which not only improved tissue stability but also provided a favorable microenvironment for cell adhesion, proliferation, and differentiation. In vitro, SAF⁺ exhibited enhanced adipogenic differentiation and superior stem cell recruitment. In vivo, SAF⁺ significantly accelerated tissue repair by promoting M2 macrophage polarization, angiogenesis, and stem cell homing. Mechanistically, these effects were mediated through activation of the integrin α2β1–FAK/Src signaling pathway. This study provides a mechanistic understanding of adipose tissue self-assembly and presents an autologous, collagen-guided approach for engineering implantable, scaffold-free adipose constructs with enhanced regenerative capacity for soft-tissue repair.</div></div><div><h3>Statement of significance</h3><div>Soft‑tissue reconstruction is hindered by unpredictable resorption and poor vascularization of autologous fat grafts. Biomaterial approaches using synthetic scaffolds or exogenous matrices often suffer biocompatibility issues, foreign‑body responses, and limited integration. We identify an intrinsic, type I collagen–driven self‑assembly capacity in human lipoaspirate and establish a collagen-guided, scaffold-free adipose strategy. By elucidating collagen signaling via integrin α2β1–FAK/Src axis, we link structural consolidation, mechanical tuning, and a pro‑regenerative microenvironment. Modulating collagen availability and crosslinking strengthens cohesion while preserving implantability and handling. The resulting constructs maintain adipose lineage, support vascularization, and integrate with host tissue. Bypassing synthetic scaffolds, this platform advances ECM‑guided assembly and offers a practical, autologous approach to soft‑tissue repair with improved handling, stability, and translational potential.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 310-326"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032041","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}
Despite therapeutic advancements in the management of Renal Cell Carcinoma (RCC), there is an unmet clinical need for patient-specific in vitro models that can predict responses to therapy and enhance our understanding of this heterogeneous disease. Here, we established biomimetic 3D in vitro models, termed tumouroids, that incorporate patient-derived tumour cells and a complex stroma to mimic the physiological tumour microenvironment. We isolated tumour cells from RCC surgical specimens (n = 20) using a mechanical-enzymatic method. Two tumouroid types were manufactured: simple tumouroids consisting of patient-derived tumour cells, collagen and matrix proteins, and complex tumouroids that incorporated an additional stromal compartment populated with fibroblasts and endothelial cells. An important feature of tumouroids is that owing to fabrication via plastic compression their density mimics in vivo physiological tissue density. Patient-derived cells and tumouroids were characterised through immunofluorescence and histology to investigate resemblance to original tissues. Finally, tumouroids were subjected to treatment with Pazopanib (Votrient™), a tyrosine kinase inhibitor (TKI) used in the treatment of advanced RCC. Patient-derived tumouroids maintained the expression of characteristic RCC protein markers: carbonic anydrase IX (CA9), cytokeratins (CK7, CK8&18) and EMT markers (αSMA). The subtype-specific histology of the original tumour, e.g., clear cell, was also preserved. We observed Pazopanib-induced cytotoxicity, as measured by ATP production, ranging from none to strong (40 %) for individual patient-derived simple tumouroids (n = 12). In complex tumouroids, endothelial networks were also disrupted. Overall, patient-derived tumouroids mimicked the original tissue and successfully reproduced the response signatures to TKIs.
Statement of significance
A significant number of renal cell carcinoma patients do not respond to targeted therapies or develop resistance and succumb to the disease. Here, we developed sophisticated 3D in vitro tumour models, termed tumouroids, from patient samples. Tumouroids mimic the original tumour and its microenvironment and elicit response to drugs that target both the tumour cells and the tumour microenvironment. This is a patient-specific in vitro tool that addresses the unmet clinical need for predicting an individual’s response to therapy.
尽管肾细胞癌（RCC）的治疗取得了进展，但临床对患者特异性体外模型的需求尚未得到满足，这些模型可以预测对治疗的反应，并增强我们对这种异质性疾病的理解。在这里，我们建立了被称为类肿瘤的仿生3D体外模型，其中包括患者来源的肿瘤细胞和复杂的基质来模拟生理肿瘤微环境。我们使用机械酶法从RCC手术标本（n=20）中分离肿瘤细胞。我们制造了两种类型的类肿瘤：由患者来源的肿瘤细胞、胶原蛋白和基质蛋白组成的简单类肿瘤，以及由成纤维细胞和内皮细胞组成的附加间质室组成的复杂类肿瘤。类肿瘤的一个重要特征是，由于通过塑料压缩制造，它们的密度模仿体内生理组织密度。通过免疫荧光和组织学对患者来源的细胞和类肿瘤进行表征，以研究其与原始组织的相似性。最后，类肿瘤接受Pazopanib （Votrient™）治疗，这是一种酪氨酸激酶抑制剂（TKI），用于治疗晚期RCC。患者源性类肿瘤保持了典型RCC蛋白标志物的表达：碳anydrase IX （CA9）、细胞角蛋白（CK7、ck8和18）和EMT标志物（αSMA）。原始肿瘤的亚型特异性组织学，如透明细胞，也被保留。我们观察到pazopanib诱导的细胞毒性，通过ATP的产生来测量，对于单个患者来源的单纯性类肿瘤（n=12），从无到强（40%）不等。在复杂的类肿瘤中，内皮网络也被破坏。总的来说，患者衍生的类肿瘤模拟了原始组织，并成功地复制了对TKIs的反应特征。意义声明：相当数量的肾细胞癌患者对靶向治疗没有反应或产生耐药性并死于疾病。在这里，我们从患者样本中开发了复杂的3D体外肿瘤模型，称为类肿瘤。类肿瘤模拟原始肿瘤及其微环境，并引发对靶向肿瘤细胞和肿瘤微环境的药物的反应。这是一种患者特异性体外工具，用于预测个体对治疗反应的未满足临床需求。
{"title":"Establishment of patient-derived 3D tumouroids: Personalised medicine tools for renal cancer","authors":"Kalliopi Bokea , Tayebeh Azimi , Katerina Stamati , William Braithwaite , Ebrahim Abdal , Rifat Hamoudi , Faiz Mumtaz , Elnaz Yaghini , Alexander J MacRobert , Umber Cheema , Maxine GB Tran , Marilena Loizidou","doi":"10.1016/j.actbio.2025.12.033","DOIUrl":"10.1016/j.actbio.2025.12.033","url":null,"abstract":"<div><div>Despite therapeutic advancements in the management of Renal Cell Carcinoma (RCC), there is an unmet clinical need for patient-specific <em>in vitro</em> models that can predict responses to therapy and enhance our understanding of this heterogeneous disease. Here, we established biomimetic 3D <em>in vitro</em> models, termed tumouroids, that incorporate patient-derived tumour cells and a complex stroma to mimic the physiological tumour microenvironment. We isolated tumour cells from RCC surgical specimens (<em>n</em> = 20) using a mechanical-enzymatic method. Two tumouroid types were manufactured: simple tumouroids consisting of patient-derived tumour cells, collagen and matrix proteins, and complex tumouroids that incorporated an additional stromal compartment populated with fibroblasts and endothelial cells. An important feature of tumouroids is that owing to fabrication via plastic compression their density mimics <em>in vivo</em> physiological tissue density. Patient-derived cells and tumouroids were characterised through immunofluorescence and histology to investigate resemblance to original tissues. Finally, tumouroids were subjected to treatment with Pazopanib (Votrient™), a tyrosine kinase inhibitor (TKI) used in the treatment of advanced RCC. Patient-derived tumouroids maintained the expression of characteristic RCC protein markers: carbonic anydrase IX (CA9), cytokeratins (CK7, CK8&18) and EMT markers (αSMA). The subtype-specific histology of the original tumour, e.g., clear cell, was also preserved. We observed Pazopanib-induced cytotoxicity, as measured by ATP production, ranging from none to strong (40 %) for individual patient-derived simple tumouroids (<em>n</em> = 12). In complex tumouroids, endothelial networks were also disrupted. Overall, patient-derived tumouroids mimicked the original tissue and successfully reproduced the response signatures to TKIs.</div></div><div><h3>Statement of significance</h3><div>A significant number of renal cell carcinoma patients do not respond to targeted therapies or develop resistance and succumb to the disease. Here, we developed sophisticated 3D <em>in vitro</em> tumour models, termed tumouroids, from patient samples. Tumouroids mimic the original tumour and its microenvironment and elicit response to drugs that target both the tumour cells and the tumour microenvironment. This is a patient-specific <em>in vitro</em> tool that addresses the unmet clinical need for predicting an individual’s response to therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 373-382"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783876","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}
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