Acta Biomaterialia最新文献

{"title":"Unexplained infertility and impaired decidualization: A case for studying endometrial mechanics and microstructure","authors":"Catalina S. Bastías ,&nbsp;Matthew Dean ,&nbsp;Callan M. Luetkemeyer","doi":"10.1016/j.actbio.2025.11.026","DOIUrl":"10.1016/j.actbio.2025.11.026","url":null,"abstract":"<div><div>Unexplained infertility affects approximately 20 % of couples seeking reproductive assistance, often leading to the use of treatments such as in vitro fertilization (IVF) despite their limited efficacy in these cases. Emerging evidence implicates endometrial dysfunction – specifically impaired decidualization – as an underlying cause. The endometrium is the inner lining of the uterus that undergoes cyclical regeneration, breakdown, and repair during the menstrual cycle, and plays a critical role in embryo implantation and early pregnancy. Decidualization is a hormonally driven transformation of the endometrium involving dramatic cellular and extracellular matrix (ECM) changes essential for successful implantation and pregnancy. While the cellular and hormonal aspects of decidualization have been studied extensively, the required alterations to ECM composition, organization, and mechanical function remain largely unknown. This review summarizes the current knowledge about the anatomy, structure, composition, and mechanical function of the uterus, with a particular focus on the endometrium throughout the menstrual cycle and during pregnancy. A special focus is placed on the role of the ECM in impaired decidualization, a key contributor to endometrial dysfunction. We suggest that an interdisciplinary approach, integrating insights from reproductive physiology, ECM biology, imaging science, and engineering mechanics, will enable a more complete understanding of reproductive function and dysfunction, leading to improved diagnostics and more targeted therapies for infertility.</div></div><div><h3>Statement of significance</h3><div>Unexplained infertility affects millions of couples, often leading to costly and ineffective treatments like IVF. Emerging research implicates endometrial dysfunction—specifically, impaired decidualization—as a key contributor. While hormonal and cellular aspects of this process are well-studied, the role of the extracellular matrix (ECM) in supporting implantation remains largely unknown. This review presents a comprehensive synthesis of endometrial anatomy, microstructure, and mechanics, highlighting novel interdisciplinary opportunities that combine reproductive biology with engineering and imaging science. By emphasizing mechanical biomarkers and ECM remodeling, this work lays a foundation for new diagnostic tools and therapies that could transform how we identify and treat infertility, offering hope to those with unexplained reproductive challenges.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 89-101"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566783","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":"Inter-spheroid proximity and matrix remodeling determine cancer associated fibroblast mediated cancer cell invasion","authors":"Pranav Mehta ,&nbsp;Ankur Deep Bordoloi ,&nbsp;Cor Ravensbergen ,&nbsp;Ma.Kristen H. David ,&nbsp;Wilma Mesker ,&nbsp;Gerrit Jan Liefers ,&nbsp;Peter ten Dijke ,&nbsp;Pouyan E. Boukany","doi":"10.1016/j.actbio.2025.11.027","DOIUrl":"10.1016/j.actbio.2025.11.027","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Breast cancer is the most commonly diagnosed malignancy worldwide, with molecular subtypes following distinct clinical trajectories. While Luminal A breast cancers are typically indolent, a subset enriched in α-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs) exhibits aggressive behavior, facilitating tumor invasion. However, the biophysical mechanisms by which CAFs drive invasion and extracellular matrix (ECM) remodeling remain unclear. In addition, the temporal and spatial dynamics of CAF interactions with the collagen matrix and cancer cell spheroids remain unknown, raising the question of whether these processes follow a deterministic sequence or occur stochastically. To address this, we conducted histological analysis of Luminal A tumors, which revealed variation in CAF, cancer cell, and ECM organization at tumor boundaries. To assess the impact of CAF on cancer cell invasion, we use a 3D &lt;em&gt;in-vitro&lt;/em&gt; model co-embedding 19TT breast CAF and MCF7 luminal breast cancer spheroids within a three-dimensional (3D) collagen-I hydrogel and performed time-lapse imaging. We demonstrate that inter-spheroid distance critically determines 19TT CAF-induced MCF7 spheroid behavior. Moreover, we showed that CAF-mediated collagen matrix remodeling and degradation precede the observed MCF7 spheroid disruption and are critical in promoting cancer cell spheroid expansion and cell dissemination. While broad-spectrum matrix metalloproteinase inhibition suppressed CAF-driven collagen degradation and MCF7 spheroid expansion, it did not prevent ECM remodeling, CAF migration, or single-cell dissemination of cancer cell spheroids. Furthermore, a complementary heterospheroid model revealed similar ECM remodeling and invasion dynamics despite the altered cellular arrangement of cancer cells and CAFs. Our findings enhance our understanding of the relationship between CAF activity and collagen matrix remodeling processes that promote cancer cell invasion, providing insights into the potential therapeutic benefits of targeting CAFs in breast cancer treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of Significance&lt;/h3&gt;&lt;div&gt;This research provides key insights into breast cancer-associated fibroblasts (CAFs) mediated remodeling of the extracellular matrix (ECM) and subsequent breast cancer cell dissemination and invasion. Herein, we demonstrated that CAFs remodel collagen fibres before migration and matrix metalloproteinase (MMP)-mediated degradation. Using a 3D in-vitro model, we showed that distinct mechanisms govern cancer cell spheroid expansion and single-cell dissemination: while expansion depends on collagen matrix integrity, dissemination relies on CAF-driven collagen remodeling. These findings advance our understanding of the relationship between CAF activity and collagen matrix remodeling processes that promote cancer cell invasion, providing insights into the potential therapeutic benefits of targeting CAFs in breast cancer treatment.&lt;/","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 350-361"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575007","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":"Targeting cuproptosis with nanomaterials for cancer immunotherapy","authors":"Pan-Pan Cui,&nbsp;Qi-Chao Yang,&nbsp;Zhi-Jun Sun","doi":"10.1016/j.actbio.2025.11.028","DOIUrl":"10.1016/j.actbio.2025.11.028","url":null,"abstract":"<div><div>Cancer immunotherapy has changed the landscape of tumor treatment. However, its efficacy is often limited by low response rates and drug resistance, especially in immunologically cold tumors. The recent discovery of cuproptosis, a distinct form of copper ion induced programmed cell death, has unveiled a promising strategy to surmount these challenges. Cuproptosis instigates immunogenic cell death, activates the cGAS-STING pathway, and remodels the tumor microenvironment, thereby augmenting antitumor immunity. This review systematically examines the molecular mechanisms of cuproptosis, its regulatory pathways, and synergistic interactions with antitumor immunity. To address the complexity of tumor cell copper efflux mechanisms and microenvironmental barriers, nanomaterials have been innovatively employed for cuproptosis regulation through their advantages in precise targeting, intelligent responsiveness, and multifunctional integration. The review highlights cutting-edge design strategies including mesoporous frameworks and biomimetic nanomaterials. Notably, the crosstalk between cuproptosis and other cell death pathways (such as ferroptosis and pyroptosis), along with its synergistic effects with immune checkpoint blockade, provides multidimensional approaches to overcome tumor resistance. The review further explores the translational potential of cuproptosis from fundamental mechanisms to clinical applications. It synthesizes recent advances in copper homeostasis regulation, multi-omics analytical approaches, cell death interactions, artificial intelligence applications, and precision-targeted delivery systems. This comprehensive analysis aims to provide theoretical support for designing stable and efficient cuproptosis-inducing materials and enhancing the therapeutic efficacy of cancer immunotherapy.</div></div><div><h3>Statement of significance</h3><div>This review systematically summarizes the molecular mechanisms and regulatory pathways of cuproptosis and highlights its synergistic effects with anti-tumor immunity, including M1 macrophage polarization, cGAS-STING pathway activation, and alleviation of the immunosuppressive tumor microenvironment. It provides a detailed overview of nanomaterial-based strategies to induce cuproptosis, covering both endogenous and exogenous copper-based approaches. Potential synergistic interactions with other regulated cell death pathways, such as ferroptosis and pyroptosis, as well as immune checkpoint blockade, are discussed. Clinical translation, challenges in future applications, and therapeutic optimization are addressed, integrating mechanistic insights and nanomaterial strategies, providing a reference for future research on cuproptosis in cancer therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 38-63"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575041","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":"Corrigendum to “Biodegradable Magnesium alloy Janus membrane with surface-selective osteoinduction and soft tissue healing properties in guided bone regeneration” [Acta Biomaterialia 195 (2025) 582-598]","authors":"Yujia Han ,&nbsp;Xiaoxia Wang ,&nbsp;Penggong Wei ,&nbsp;Dan Zhang ,&nbsp;Ming Gao ,&nbsp;Zihang Yu ,&nbsp;Qiang Wang ,&nbsp;Lili Tan ,&nbsp;Yulou Tian","doi":"10.1016/j.actbio.2025.11.011","DOIUrl":"10.1016/j.actbio.2025.11.011","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"208 ","pages":"Pages 598-600"},"PeriodicalIF":9.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552007","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":"Self-adaptive 3D-printed PCLA/BCP scaffolds functionalized using vapor etching and nanocoating for immunomodulatory and antibacterial bone regeneration","authors":"Jian He ,&nbsp;Liang Qiao ,&nbsp;Yixuan Lan ,&nbsp;Chao Peng ,&nbsp;Qizhi Fu ,&nbsp;Xin Dai ,&nbsp;Zhen Fan ,&nbsp;Hai Lan ,&nbsp;Sanqiang Li ,&nbsp;Xiangchun Zhang ,&nbsp;Xulin Hu","doi":"10.1016/j.actbio.2025.11.022","DOIUrl":"10.1016/j.actbio.2025.11.022","url":null,"abstract":"<div><div>Integrating immunomodulatory and antibacterial functions into bone scaffolds is crucial for effective bone regeneration, especially in infection-prone clinical settings. This strategy enhances healing, reduces postoperative infection risk, and improves implant osseointegration. Here, we developed a 3D-printed scaffold with shape-memory, immunomodulatory, and antibacterial capabilities. The scaffold was fabricated by dissolving poly(caprolactone-co-lactic acid) in dioxane and incorporating biphasic calcium phosphate, followed by low-temperature 3D printing, freeze-drying, and surface etching with vapor-phase ethanol–acetic acid to enhance roughness. γ-Cyclodextrin/tea polyphenol–magnesium nanoparticles were then immobilized on the scaffold surface to create a pH-responsive system for dual sustained release. Tea polyphenols provided broad-spectrum antibacterial activity, including against methicillin-resistant <em>Staphylococcus aureus</em>, while Mg²⁺ promoted M2 macrophage polarization to modulate the immune microenvironment. Surface characterization confirmed enhanced hydrophilicity and cell adhesion. In vitro studies demonstrated inhibition of bacterial biofilms, along with improved cell proliferation and osteogenic differentiation. In vivo evaluation in an MRSA-infected rat femoral defect model showed reduced local inflammation and enhanced vascularized bone regeneration. This multifunctional scaffold design synergizes physical adaptability with bioactive regulation, offering a promising therapeutic strategy for the repair of infected bone defects.</div></div><div><h3>Statement of significance</h3><div>This study introduces a self-adaptive 3D-printed scaffold designed for bone regeneration in infection-prone environments. Constructed from PCLA and BCP, the scaffold integrates shape memory properties with antibacterial and immunomodulatory functions. Incorporation of γ-cyclodextrin/tea polyphenol-magnesium complexes enables sustained, pH-responsive release of bioactive agents that suppress bacterial growth, promote angiogenesis, and induce M2 macrophage polarization. Vapor-phase etching enhances surface roughness and hydrophilicity, improving cellular adhesion and nutrient exchange. In vitro studies confirmed antibacterial efficacy, immune modulation, and osteogenic promotion, while in a rat MRSA-infected femoral defect model, the scaffold reduced inflammation, supported vascularized bone formation, and accelerated healing, highlighting its strong translational potential.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 375-390"},"PeriodicalIF":9.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534153","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":"Injectable zwitterionic hydrogels for biomedical applications: design strategies and emerging trends","authors":"Zihao Zhu ,&nbsp;Jian Ji ,&nbsp;Peng Zhang","doi":"10.1016/j.actbio.2025.11.023","DOIUrl":"10.1016/j.actbio.2025.11.023","url":null,"abstract":"<div><div>Zwitterionic hydrogels have been extensively utilized in the biomedical field owing to their biocompatibility and immunocompatibility. The zwitterionic polymers that constitute these hydrogels possess electrically neutral yet highly polar structures, which facilitate the formation of a stable hydration layer via ionic solvation. This robust hydration layer imparts effective antifouling properties and low immunogenicity, making zwitterionic hydrogels highly suitable for in vivo applications, particularly in tissue repairing and drug/cell delivery applications. Conventional zwitterionic hydrogels typically require invasive surgical implantation and often exhibit poor integration with surrounding tissues. Injectable zwitterionic hydrogels (IZHs) have demonstrated advantages in overcoming these limitations, but their design remains challenging. This review outlines the structural features, design strategies, and biomedical applications of IZHs. Current challenges and future directions are also discussed to advance the clinical translation of this next-generation hydrogel platform.</div></div><div><h3>Statement of significance</h3><div>This Review provides a systematic overview of injectable zwitterionic hydrogels (IZHs), focusing on their design principles, material properties, and potential biomedical applications. Unlike previous reviews on non-injectable hydrogels, it concentrates on IZHs, a rapidly emerging class of biomaterials that combine the intrinsic advantages of zwitterionic polymers—low immunogenicity, good biocompatibility, and antifouling performance—with features such as in situ gelation, conformal integration with irregular tissues, and minimally invasive delivery. By connecting fundamental polymer design to practical biomedical applications, this Review addresses a gap in the literature and highlights the translational potential of IZHs for both research and clinical use.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 1-22"},"PeriodicalIF":9.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534062","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":"Erratum to “Elastic strain and strength–elongation performance of medium-entropy Zr–Nb–Ti–O alloys for bone implants” [Acta Biomaterialia 198 (2025) 530–545]","authors":"Zhaolin Hua ,&nbsp;Dechuang Zhang ,&nbsp;Lin Guo ,&nbsp;Sihan Lin ,&nbsp;Xiaokai Zhang ,&nbsp;Yuncang Li ,&nbsp;Cuie Wen","doi":"10.1016/j.actbio.2025.11.001","DOIUrl":"10.1016/j.actbio.2025.11.001","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"208 ","pages":"Page 597"},"PeriodicalIF":9.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515237","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":"Dynamic cell patterning and photopolymerization with electric field modulation for constructing hierarchical tumor microenvironments","authors":"Anping Wu ,&nbsp;Yanfeng Zhao ,&nbsp;Xinyi Dong ,&nbsp;Jiaxin Liu ,&nbsp;Zhiqiang Zheng ,&nbsp;Qing Shi ,&nbsp;Toshio Fukuda ,&nbsp;Huaping Wang","doi":"10.1016/j.actbio.2025.11.020","DOIUrl":"10.1016/j.actbio.2025.11.020","url":null,"abstract":"<div><div>Engineered tumor models that replicate the hierarchical, heterogeneous microenvironment of in vivo tumors have shown huge potential in biomedical and clinical research. Tumor spheroids are widely used as in vitro models to investigate tumor pathophysiology. However, due to the complex cell–cell and cell-extracellular matrix (ECM) interactions in native tumor tissues, tumor spheroids alone often fail to replicate the intricate architecture and functionality of the tumor microenvironment (TME). Here, we propose a versatile strategy that assembles tumor spheroids while simultaneously constructing individualized ECM-mimicking environments, thereby more accurately replicating the native hierarchical TME. By applying a uniform electric field, the wettability of cell-laden hydrogel droplets is modulated, enabling their transport to predefined locations. Once positioned, a non-uniform electric field induces dielectrophoresis (DEP), guiding the cells to aggregate into tumor spheroids following predefined patterns. A digital micromirror device (DMD) then dynamically controls the shape and position of ultraviolet (UV) patterns, triggering photopolymerization of the hydrogel and precisely encapsulating the cell spheroids, thereby forming tumor models. In our experiment, breast cancer and liver cancer cells were aggregated to form tumor spheroids that maintained high cell viability, proliferative capacity, and morphological regularity, with the spheroid circularity reaching 0.84. Furthermore, when liver cancer spheroids were encapsulated in hydrogels containing endothelial cells, their invasiveness increased by approximately 77 %. We anticipate that our method will be capable of regenerating more complex tumor models with unprecedented possibilities for future drug discovery.</div></div><div><h3>Statement of significance</h3><div>Reconstructing a hierarchical tumor microenvironment (TME) requires not only the formation of cell aggregates with natural intercellular connections but also the precise spatial organization of stromal cells and extracellular matrix components (ECM). However, achieving such dynamic cellular assembly and controllable heterogeneity during bioprinting remains challenging. Here, we present a multifunctional strategy that integrates dielectrophoretic droplet manipulation into a 3D bioprinting system to induce the in situ formation of compact, viable, and uniform tumor spheroids. Bioinks containing ECM components and stromal cells are then spatially patterned and photopolymerized with high precision to build customizable, biomimetic TMEs. This approach provides a versatile and controllable platform for drug screening, cancer research, and personalized medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 339-349"},"PeriodicalIF":9.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531023","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":"Nanobody-based high-performance multitarget immunosorbents protect against sepsis by concurrently adsorbing endotoxins and inflammatory cytokines","authors":"Lichun Wang ,&nbsp;Yu Ding ,&nbsp;FangFei Xue ,&nbsp;Nan Li ,&nbsp;Yunzheng Du ,&nbsp;Biao Wang ,&nbsp;Yamin Chai ,&nbsp;Zuoliang Dong ,&nbsp;Lailiang Ou","doi":"10.1016/j.actbio.2025.11.016","DOIUrl":"10.1016/j.actbio.2025.11.016","url":null,"abstract":"<div><div>Sepsis, a life-threatening disease caused by severe infections, affects over 40 million people worldwide annually, with high mortality rates in intensive care units. Bacterial endotoxins and cytokine storms induced by infection are two primary therapeutic targets for sepsis management. Recent advances in biomaterials have offered many promising opportunities for treating infectious and inflammatory diseases, particularly hemoperfusion adsorbents. However, simultaneously attenuating endotoxin levels and cytokine storms in whole blood directly by hemoperfusion remains clinically challenging due to the distinct physicochemical properties (charge and size) of endotoxins and cytokines. Herein, we report a multitarget immunosorbent designed to combat sepsis, constructed by conjugating an anti-tumor necrosis factor-α nanobody to <span>l</span>-arginine functionalized polystyrene resin (PS-Arg-Nb). This system provides abundant binding sites for both endotoxins and multiple cytokines while maintaining excellent biocompatibility. By concurrently and efficiently adsorbing endotoxins and inflammatory cytokines, the PS-Arg-Nb immunosorbent significantly reduced immune cell infiltration in various organs and helped alleviate organ damage, consequently improving survival rates in a rat sepsis model. This multitarget immunosorbents strategy offers significant advantages in design, efficiency, and biosafety, presenting a promising therapeutic approach for sepsis and other inflammatory diseases.</div></div><div><h3>Statement of significance</h3><div>Sepsis remains lethal with limited treatments addressing both endotoxins and cytokines. We developed a multitarget nanobody-based immunosorbent (PS-Arg-Nb) that synergistically captures endotoxins (2211.77 EU/g) and cytokines (e.g., 92.10 % TNF-α removal) via arginine modification, nanobody recognition, and mesoporous adsorption. It demonstrates rapid clearance, improves survival by &gt;40 % in septic rats, and exhibits excellent biocompatibility. This strategy offers a safe and efficient hemoperfusion solution for sepsis therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 532-546"},"PeriodicalIF":9.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531036","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":"Multi-omics qualification of an organ-on-a-chip model of osteolytic bone metastasis","authors":"Natalia Munoz Castro ,&nbsp;Joanne Nolan ,&nbsp;Eleni Maniati ,&nbsp;Ayushi Agrawal ,&nbsp;Valentine Gauthier ,&nbsp;Oliver M.T. Pearce ,&nbsp;Stefaan W. Verbruggen ,&nbsp;Martin M. Knight","doi":"10.1016/j.actbio.2025.11.018","DOIUrl":"10.1016/j.actbio.2025.11.018","url":null,"abstract":"<div><div>Bone is a primary site for metastasis in breast cancer, with up to 70 % of patients with metastatic breast cancer developing osteolytic bone lesions, wherein cancer cells drive osteoclast resorption of bone. However, progress in developing therapies is limited by the absence of predictive <em>in vitro</em> models. This study developed a unique organ-on-a-chip model to simulate osteolytic bone metastasis and utilised a multi-omics approach for characterisation/qualification and validation against <em>in vivo</em> data. Using the Emulate S1 platform, we co-cultured murine osteocytes and osteoclasts to recreate the bone microenvironment, alongside breast cancer cells in a separate channel separated by a porous membrane. Using RNA sequencing, cytokine profiling, and fluorescence staining, we demonstrated the importance of the complete tri-culture model in replicating key aspects of <em>in vivo</em> biology, and uncovered critical pathways involved in metastasis. A synergistic effect was observed in the tri-culture organ-chip model, leading to increased cancer cell migration and the upregulation of pro-metastatic and pro-inflammatory pathways that promote bone degradation and cancer progression. This study validates an organ-chip model of osteolytic breast cancer bone metastasis as a scalable alternative to traditional animal models. Furthermore, we show how multi-omics and bioinformatics techniques may be used for qualification and validation of organ-chip models; for unpicking the relative contribution of the different cell types; and to identify signalling pathways and therapeutic targets.</div></div><div><h3>Statement of significance</h3><div>In this study, we develop a 3D organ-on-a-chip tri-culture model of the osteolytic metastatic niche, in which we verify expected bone and breast cancer cell behaviours. Importantly, we successfully validate our organ-chip against a dataset from the gold standard <em>in vivo</em> preclinical model of osteolytic breast metastases, using transcriptomics and proteomics to confirm strong alignment of gene expression profiles with <em>in vivo</em> mouse expression. Additionally, our multi-omics analysis sheds new light on both expected and novel molecular pathways for therapeutic targeting, demonstrating the utility of the organ-chip as a potential replacement for preclinical mouse models of breast cancer metastases in bone.</div><div>Therefore, this study represents a key marker in the field of organ-chip research, demonstrating the importance of biomaterials technologies for preclinical science. Most importantly, our work demonstrates for biotech and pharma companies that qualified organ-chip devices can play a role as intermediate medium-throughput technologies for screening lead drug candidates.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 362-374"},"PeriodicalIF":9.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531028","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}