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Acta Biomaterialia最新文献

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Engineered cerium oxide nanoparticles conjugated with carrier platforms: Therapeutic mechanisms for skin wound healing applications 与载体平台结合的工程氧化铈纳米颗粒:皮肤伤口愈合应用的治疗机制。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.016
Tzong-Yun Ger , Seyyed Mojtaba Mousavi , Chia-Jung Yang , Chun-Hsu Yao , Jui-Yang Lai
Wound healing is a complex process influenced by oxidative stress, inflammation, microbial infection, and limited angiogenesis. Conventional therapies often fail to address these multifactorial barriers, prompting the need for advanced, multifunctional platforms. This review summarizes recent advances in cerium oxide nanoparticles (CeO2 NPs) combined with carrier platforms, providing a mechanistic framework for their wound-healing applications. Unlike earlier reviews focusing on either NPs or carrier platforms alone, this work integrates both areas to show how CeO2 NPs in hydrogels, nanofibers, cryogels, and composites improve release control, biocompatibility, and targeted therapeutic performance. The review highlights CeO2 NPs’ reversible Ce3+/Ce4+ cycling, enabling reactive oxygen species (ROS) scavenging, inflammation control, antibacterial action, and angiogenesis promotion. It categorizes wound types (diabetic, burn, infected, and post-surgical) and maps CeO2 NP-based interventions to their corresponding pathological features, providing translational insights for clinical applications. Furthermore, it discusses synthesis methods, physicochemical characterization, and biological mechanisms, serving as a strategic resource for both researchers and clinicians. By bridging nanomedicine and regenerative biomaterials, this review presents a framework for designing smart wound-healing systems that address molecular dysfunction and structural repair, guiding future research toward both clinical translation, personalized therapies and the optimization of NP– carrier platforms interactions.

Statement of significance

The development of cerium oxide nanoparticles (CeO2 NPs) conjugated with carrier platforms has opened new avenues for skin wound healing. These nanoplatforms have demonstrated significant potential in reducing oxidative stress, suppressing inflammation, preventing infection, and promoting angiogenesis, thereby accelerating tissue regeneration and enhancing therapeutic efficacy. While most existing reviews have emphasized the individual effects of nanoparticles, the synergistic benefits arising from delivery-system conjugation have often been overlooked. This review comprehensively summarizes studies describing the mechanistic roles of CeO2–based delivery platforms in advanced wound-healing applications. Furthermore, synthesis strategies, physicochemical characteristics, and biological mechanisms are discussed. Finally, A concise commentary on future prospects for researchers across regenerative medicine and biomedical science.
伤口愈合是一个复杂的过程,受氧化应激、炎症、微生物感染和有限的血管生成的影响。传统疗法往往无法解决这些多因素障碍,这促使人们需要先进的多功能平台。本文综述了氧化铈纳米颗粒(CeO2 NPs)与载体平台结合的最新进展,为其伤口愈合应用提供了一个机制框架。不同于以往的综述只关注纳米粒子或载体平台,本研究将这两个领域整合在一起,展示了水凝胶、纳米纤维、冷冰和复合材料中CeO2纳米粒子如何改善释放控制、生物相容性和靶向治疗性能。该综述强调了CeO2 NPs的可逆Ce3+/Ce4+循环,能够清除活性氧(ROS),控制炎症,抗菌作用和促进血管生成。它对伤口类型(糖尿病、烧伤、感染和术后)进行了分类,并将基于CeO2 np的干预措施映射到相应的病理特征,为临床应用提供了转化见解。此外,它还讨论了合成方法,物理化学特性和生物学机制,作为研究人员和临床医生的战略资源。通过连接纳米医学和再生生物材料,本文提出了一个设计智能伤口愈合系统的框架,解决分子功能障碍和结构修复问题,指导未来临床翻译、个性化治疗和优化NP载体平台相互作用的研究。意义声明:与载体平台结合的氧化铈纳米颗粒(CeO2 NPs)的发展为皮肤伤口愈合开辟了新的途径。这些纳米平台在减少氧化应激、抑制炎症、预防感染和促进血管生成方面具有显著的潜力,从而加速组织再生和提高治疗效果。虽然大多数现有的评论都强调了纳米颗粒的个体效应,但通常忽略了由递送系统偶联产生的协同效益。本文全面总结了基于ceo2的递送平台在高级伤口愈合应用中的机制作用的研究。此外,还讨论了合成策略、理化特性和生物机理。最后,对再生医学和生物医学研究人员的未来前景进行了简要的评论。
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引用次数: 0
Minipig costal and knee cartilage structure-function relationships and their use as cell sources for tissue-engineered analogous cellular products for cartilage repair 小型猪肋和膝关节软骨结构-功能关系及其作为软骨修复组织工程类似细胞产品的细胞来源。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.023
Gaston A. Otarola , Rachel C. Nordberg , Jerry C. Hu, Kyriacos A. Athanasiou
Toward the development of biologic products intended to repair articular cartilage, this study evaluated native structure-function relationships of rib and knee cartilage and compared the capacity of articular chondrocytes (ACs) and costochondral cells (CCs) to generate tissue-engineered analogous cellular products (ACPs) for preclinical cartilage repair studies. Utilizing the relevant preclinical model of the Yucatan minipig, both knee and rib cartilages were characterized by topography and age. Key findings include that: 1) knee cartilage had higher tensile properties than rib cartilage (e.g., ultimate tensile strength of adult knee cartilage being 218 % of adult rib cartilage), 2) rib cartilage had higher compressive properties than knee cartilage (e.g., aggregate modulus of adult rib cartilage being 177 % of adult knee cartilage), 3) functional (i.e., biomechanical and biochemical) properties were dependent on age (e.g., adult coefficient of friction being 186 % of that of the juvenile in the medial-lateral axis of the knee), 4) functional properties were dependent on topography, 5) compressive properties were significantly correlated to glycosaminoglycan content and hydration, and 6) tensile properties were significantly correlated to collagen content. Additionally, juvenile ACs and CCs were compared for their capacity to generate self-assembled neocartilage with constructs achieving functionality index values (i.e., a weighted average of neocartilage functional properties compared to native tissue) of 0.54 and 0.44, respectively, when compared to native adult minipig knee cartilage. Overall, this study provides gold-standard characterization values for minipigs of different ages for preclinical cartilage repair studies and demonstrates that both ACs and CCs can be used to generate functional self-assembled neocartilage ACPs.

Statement of significance

Toward the clinical translation of tissue-engineered cartilage implants, this study characterizes the functional properties of knee and rib cartilage in the clinically relevant Yucatan minipig model. Additionally, it evaluates the ability of knee- and rib-derived chondrocytes to generate neocartilage that recapitulates the functional properties of native cartilage tissues. Age-related changes in rib and knee cartilage are also described, along with structure-function relationships involving correlating biochemical composition and mechanical properties of cartilage tissues. Overall, this study provides data essential to the translation of cartilage implants for the knee and describes how these data are relevant to the FDA regulatory process.
为了开发用于修复关节软骨的生物制品,本研究评估了肋骨和膝关节软骨的天然结构-功能关系,并比较了关节软骨细胞(ACs)和肋软骨细胞(CCs)产生用于临床前软骨修复研究的组织工程类似细胞产品(ACPs)的能力。利用尤卡坦迷你猪的相关临床前模型,对其膝关节和肋骨软骨进行地形和年龄表征。主要发现包括:1)膝关节软骨的抗拉性能高于肋骨软骨(例如,成人膝关节软骨的极限抗拉强度是成人肋骨软骨的218%),2)肋软骨的抗压性能高于膝关节软骨(例如,成人肋骨软骨的聚集模量是成人膝关节软骨的177%),3)功能(即生物力学和生化)性能依赖于年龄(例如,成人膝关节内侧-外侧轴的摩擦系数是青少年的186%),4)功能特性依赖于地形,5)压缩特性与糖胺聚糖含量和水合作用显著相关,6)拉伸特性与胶原蛋白含量显著相关。此外,与原生成年迷你猪膝关节软骨相比,幼年ac和cc产生自组装新软骨的能力分别达到0.54和0.44的功能指数值(即与天然组织相比,新软骨功能特性的加权平均值)。总的来说,本研究为临床前软骨修复研究提供了不同年龄的小型猪的金标准表征值,并证明ac和cc都可以用于产生功能自组装的新软骨acp。意义声明:为了组织工程软骨植入物的临床应用,本研究在临床相关的尤卡坦迷你猪模型中表征了膝关节和肋骨软骨的功能特性。此外,它还评估了膝关节和肋骨来源的软骨细胞产生再现天然软骨组织功能特性的新软骨的能力。还描述了肋骨和膝关节软骨的年龄相关变化,以及涉及软骨组织相关生化组成和机械性能的结构-功能关系。总的来说,本研究为膝关节软骨植入物的翻译提供了必要的数据,并描述了这些数据如何与FDA监管过程相关。
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引用次数: 0
Mechanisms of anisotropic wet friction in bioinspired hexagonal pillar arrays 仿生六方柱阵列中各向异性湿摩擦机理研究。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.027
Meng Li, Maomao Zhang, Congfeng Wang, Qi Liu, Yongjian Sun, Tao Wang, Liping Shi
Anisotropic friction under wet conditions is essential for biological attachment and emerging robotic applications, yet its governing mechanisms remain unclear. Inspired by the microstructure of tree frog toe pads, hexagonal micropillar arrays with varying geometric parameters were fabricated, and their wet friction behavior was systematically investigated. The results show that the pillar aspect ratio (γ) predominantly determines directional friction performance. A pronounced friction enhancement occurs within 0.25 < γ < 0.64, with the highest anisotropy at γ = 0.375, where side-sliding friction is 126 % higher than corner-sliding. This anisotropic enhancement arises from more efficient drainage and greater dry contact formation induced by surface warping and inter-channel constriction during pillar deformation. Interference imaging and theoretical modeling confirm that anisotropic friction originates from deformation-driven modulation of the lubrication film and dry contact area. These findings elucidate the structure-function relationship of hexagonal architectures and provide design principles for engineering bioinspired surfaces with controllable friction under wet conditions.

Statement of significance

Directional friction under wet conditions is critical for biological and engineering systems that require controlled locomotion, attachment, or gripping in fluidic environments. Inspired by the hexagonal pillar arrays found on tree frog toe pads, this study elucidates the fundamental mechanisms by which aspect ratio and sliding direction govern anisotropic wet friction. By combining tribological experiments, optical interference analysis, and deformation modeling, we demonstrate that friction anisotropy arises from deformation-driven drainage - specifically, the coupled effects of inter-pillar channel contraction and top-surface warping. These insights establish a mechanistic framework linking microscale structural deformation to macroscale frictional performance, providing design principles for bioinspired surfaces with programmable friction. The findings have direct implications for soft robotics, medical tools, and wearable devices operating in wet or dynamic environments.
湿条件下的各向异性摩擦对生物附着和新兴机器人应用至关重要,但其控制机制尚不清楚。以树蛙趾垫的微观结构为灵感,制备了具有不同几何参数的六边形微柱阵列,并对其湿摩擦性能进行了系统研究。结果表明,柱长径比(γ)对定向摩擦性能的影响较大。在0.25 < γ < 0.64范围内出现明显的摩擦增强,在γ = 0.375处各向异性最大,侧滑摩擦比角滑摩擦高126%。这种各向异性增强是由于柱变形过程中地表翘曲和通道间收缩引起的更有效的排水和更大的干接触形成。干涉成像和理论建模证实了各向异性摩擦源于润滑膜和干接触面积的变形驱动调制。这些发现阐明了六边形结构的结构-功能关系,并为湿条件下具有可控摩擦的工程仿生表面提供了设计原则。意义说明:湿润条件下的定向摩擦对于需要在流体环境中控制运动、附着或夹持的生物和工程系统至关重要。受树蛙趾垫六角形柱阵列的启发,本研究阐明了纵横比和滑动方向控制各向异性湿摩擦的基本机制。通过结合摩擦学实验、光学干涉分析和变形建模,我们证明了摩擦各向异性是由变形驱动的排水引起的,特别是柱间通道收缩和顶面翘曲的耦合效应。这些见解建立了将微观结构变形与宏观摩擦性能联系起来的机制框架,为具有可编程摩擦的仿生表面提供了设计原则。这一发现对软机器人、医疗工具和在潮湿或动态环境中操作的可穿戴设备具有直接意义。
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引用次数: 0
Smooth muscle cell-like support cells accelerate the autologous endothelialization of a polyurethane scaffold for vascular engineering 平滑肌细胞样支持细胞加速血管工程用聚氨酯支架的自体内皮化。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.011
Kate D. MacQuarrie , Katya A. D’Costa , Jeremy A. Antonyshyn , Sahej K. Saini , Uros Kuzmanov , Michelle P. Bendeck , Anthony O. Gramolini , Stefan O. P․ Hofer , J. Paul Santerre
The endothelialization of vascular scaffolds, such as small-diameter grafts, has long been an obstacle in the tissue engineering field. The absence of an abundant and expandable autologous endothelial cell source, and of a viable strategy to facilitate their rapid growth, have prevented clinical adoption of endothelialized grafts. At the same time, the importance of a confluent endothelium and mechanisms to prevent graft occlusion have been recognized. Here, we report on the rapid, patient-derived endothelialization of a non-protein coated, biocompatible, and degradable polyurethane scaffold, on which adipose tissue-derived endothelial cells are co-cultured with adipose tissue-derived stromal cells, having a smooth muscle cell-like phenotype. The co-cultured endothelia are characterized using proteomic, genomic, biochemical, and histologic analyses, which demonstrate that they maintain a functional phenotype, as well as fewer inflammatory characteristics than endothelial cells cultured without support cells. Importantly, we also show that this co-culture with endothelial cells does not compromise the differentiated, contractile phenotype of, or extracellular matrix production by, the pre-differentiated support cells. Furthermore, we demonstrate that the differentiated smooth muscle cell phenotype, when combined with human monocytes, best recapitulates the protein composition of human arteries, particularly in terms of elastin production. Overall, we demonstrate the production of a patient-derived, confluent endothelium within a vascular scaffold while recapitulating the natural features key to arterial function, namely mature supporting cells, and a physiologically relevant extracellular matrix.

Statement of Significance

For small-diameter (< 6 mm) tissue-engineered vascular grafts, it has been recognized that having a confluent endothelium on the graft’s lumen, and mimicking the arterial structure and mechanical properties present in the body, are both essential for success. Our work demonstrates the ability to produce a tissue-engineered scaffold that recapitulates critical elements of an artery’s in vivo structure and is composed entirely of autologous, fat-derived cells on a degradable, biocompatible polymer. Furthermore, it shows the potential to produce a stable, confluent endothelium, maintain the differentiated character of the co-cultured supporting cells, and synthesize an appropriate extracellular matrix, all of which are key to the graft’s ability to respond to physiological cues and remain unobstructed upon implant.
血管支架的内皮化,如小直径移植物,一直是组织工程领域的一个障碍。缺乏丰富和可扩展的自体内皮细胞来源,以及促进其快速生长的可行策略,阻碍了内皮化移植的临床应用。同时,融合内皮的重要性和防止移植物闭塞的机制已经被认识到。在这里,我们报道了一种非蛋白质涂层、生物相容性和可降解的聚氨酯支架的快速、患者来源的内皮化,在该支架上,脂肪组织来源的内皮细胞与脂肪组织来源的基质细胞共同培养,具有平滑肌细胞样表型。用蛋白质组学、基因组学、生化和组织学分析对共培养的内皮细胞进行了表征,表明它们保持了功能表型,并且比没有支持细胞培养的内皮细胞具有更少的炎症特征。重要的是,我们还表明,这种与内皮细胞的共培养不会损害预分化支持细胞的分化、收缩表型或细胞外基质的产生。此外,我们证明分化的平滑肌细胞表型,当与人类单核细胞结合时,最好地概括了人类动脉的蛋白质组成,特别是在弹性蛋白产生方面。总的来说,我们证明了在血管支架内产生患者来源的融合内皮,同时概括了动脉功能的自然特征,即成熟的支持细胞和生理上相关的细胞外基质。意义声明:对于小直径(< 6mm)的组织工程血管移植物,已经认识到在移植物的管腔上有一个融合的内皮,并且模仿体内存在的动脉结构和机械特性,都是成功的必要条件。我们的工作证明了生产组织工程支架的能力,该支架概括了动脉体内结构的关键要素,并且完全由可降解的生物相容性聚合物上的自体脂肪来源细胞组成。此外,它显示出产生稳定、融合的内皮,维持共培养支持细胞的分化特性,并合成适当的细胞外基质的潜力,所有这些都是移植物对生理信号作出反应并在植入时保持畅通的关键。
{"title":"Smooth muscle cell-like support cells accelerate the autologous endothelialization of a polyurethane scaffold for vascular engineering","authors":"Kate D. MacQuarrie ,&nbsp;Katya A. D’Costa ,&nbsp;Jeremy A. Antonyshyn ,&nbsp;Sahej K. Saini ,&nbsp;Uros Kuzmanov ,&nbsp;Michelle P. Bendeck ,&nbsp;Anthony O. Gramolini ,&nbsp;Stefan O. P․ Hofer ,&nbsp;J. Paul Santerre","doi":"10.1016/j.actbio.2025.12.011","DOIUrl":"10.1016/j.actbio.2025.12.011","url":null,"abstract":"<div><div>The endothelialization of vascular scaffolds, such as small-diameter grafts, has long been an obstacle in the tissue engineering field. The absence of an abundant and expandable autologous endothelial cell source, and of a viable strategy to facilitate their rapid growth, have prevented clinical adoption of endothelialized grafts. At the same time, the importance of a confluent endothelium and mechanisms to prevent graft occlusion have been recognized. Here, we report on the rapid, patient-derived endothelialization of a non-protein coated, biocompatible, and degradable polyurethane scaffold, on which adipose tissue-derived endothelial cells are co-cultured with adipose tissue-derived stromal cells, having a smooth muscle cell-like phenotype. The co-cultured endothelia are characterized using proteomic, genomic, biochemical, and histologic analyses, which demonstrate that they maintain a functional phenotype, as well as fewer inflammatory characteristics than endothelial cells cultured without support cells. Importantly, we also show that this co-culture with endothelial cells does not compromise the differentiated, contractile phenotype of, or extracellular matrix production by, the pre-differentiated support cells. Furthermore, we demonstrate that the differentiated smooth muscle cell phenotype, when combined with human monocytes, best recapitulates the protein composition of human arteries, particularly in terms of elastin production. Overall, we demonstrate the production of a patient-derived, confluent endothelium within a vascular scaffold while recapitulating the natural features key to arterial function, namely mature supporting cells, and a physiologically relevant extracellular matrix.</div></div><div><h3>Statement of Significance</h3><div>For small-diameter (&lt; 6 mm) tissue-engineered vascular grafts, it has been recognized that having a confluent endothelium on the graft’s lumen, and mimicking the arterial structure and mechanical properties present in the body, are both essential for success. Our work demonstrates the ability to produce a tissue-engineered scaffold that recapitulates critical elements of an artery’s <em>in vivo</em> structure and is composed entirely of autologous, fat-derived cells on a degradable, biocompatible polymer. Furthermore, it shows the potential to produce a stable, confluent endothelium, maintain the differentiated character of the co-cultured supporting cells, and synthesize an appropriate extracellular matrix, all of which are key to the graft’s ability to respond to physiological cues and remain unobstructed upon implant.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 398-412"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703011","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
Matrix stiffness shapes transcriptional profiles and drug responses of pancreatic cancer cells 基质刚度影响胰腺癌细胞的转录谱和药物反应。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.020
Eleonora Peerani , Juliana B. Candido , Eleni Maniati , Elena Tomás-Bort , Shreya Sharma , Julien Clegg , Hemant M Kocher , Jun Wang , Rodrigo Curvello , Daniela Loessner
Pancreatic cancer tissues are made of different cell populations surrounded by a dense extracellular matrix. The stiff cancerous matrix impairs the diffusion of cytotoxic drugs, contributing to poor outcomes for patients. Matrix-targeting therapies normalise the extracellular matrix and, therefore, cell-matrix interactions. However, our knowledge of how matrix stiffness influences cancer cell and transcriptional dynamics and responses to anti-cancer compounds is incomplete. Here we developed a 3D cancer model to replicate the stiffness of patient-derived tissues and evaluated the effects of matrix-targeting compounds. Transcriptomic analyses showed that matrix stiffness regulated matrisome-related genes, cytokines and chemokines. The inclusion of stromal cells further increased the mechanical properties of our 3D cancer model. Treatment with the ROCK inhibitor fasudil induced matrix softening and improved sensitivity of cancer and stromal cells to cytotoxic treatment, whereas inhibition of matrix metalloproteinases disrupted cancer cell invasion. Our results indicate that matrix stiffness impacts cancer cell profiles, and targeting the cancerous matrix may lead to improved combination therapies for pancreatic cancer.

Statement of significance

Pancreatic cancers have a dense extracellular matrix that drives resistance to therapy and disease progression, yet the mechanistic links between matrix stiffness and cancer cell behaviour are unclear. We engineered a 3D cancer model based on mechanical profiling of patient tissues to investigate how matrix stiffness influences gene expression and drug response. We found that increased stiffness regulates matrisome and inflammatory genes, and that stromal-induced stiffening affects sensitivity to matrix-targeting and cytotoxic drugs. The inhibition of Rho-kinase signalling enhanced the efficacy of cytotoxic drugs. These findings establish matrix stiffness as a key factor in tumour biology and therapy response, supporting the use of our preclinical model to guide new combination treatments for pancreatic cancer, aimed at improving outcomes for patients.
胰腺癌组织由不同的细胞群组成,周围是致密的细胞外基质。僵硬的癌性基质损害了细胞毒性药物的扩散,导致患者预后不良。基质靶向治疗使细胞外基质正常化,从而使细胞-基质相互作用正常化。然而,我们对基质硬度如何影响癌细胞和转录动力学以及对抗癌化合物的反应的了解是不完整的。在这里,我们开发了一个3D癌症模型来复制患者来源的组织的刚度,并评估基质靶向化合物的效果。转录组学分析表明,基质硬度调节基质体相关基因、细胞因子和趋化因子。基质细胞的加入进一步提高了我们的3D癌症模型的力学性能。使用ROCK抑制剂法舒地尔治疗可诱导基质软化,提高癌症和基质细胞对细胞毒性治疗的敏感性,而抑制基质金属蛋白酶则会破坏癌细胞的侵袭。我们的研究结果表明,基质刚度影响癌细胞谱,靶向癌变基质可能会改善胰腺癌的联合治疗。意义声明:胰腺癌具有致密的细胞外基质,可驱动对治疗的耐药性和疾病进展,但基质硬度与癌细胞行为之间的机制联系尚不清楚。我们设计了一个基于患者组织力学分析的三维癌症模型,以研究基质刚度如何影响基因表达和药物反应。我们发现增加的僵硬调节基质和炎症基因,基质诱导的僵硬影响对基质靶向和细胞毒性药物的敏感性。rho激酶信号的抑制增强了细胞毒性药物的疗效。这些发现确立了基质刚度是肿瘤生物学和治疗反应的关键因素,支持使用我们的临床前模型来指导胰腺癌的新联合治疗,旨在改善患者的预后。
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引用次数: 0
The effect of stiffness on cell behavior and drug resistance in patient-derived breast cancer organoids 僵硬度对患者源性乳腺癌类器官细胞行为和耐药性的影响。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.026
Wonwoo Jeong , Dongju Kim , Nadeem Wajih , Hyun-Wook Kang , Marissa M. Howard-McNatt , Konstantinos Votanopoulos , Shay Soker , Sang Jin Lee
Triple-negative breast cancer (TNBC) accounts for 10–15 % of breast cancer cases and is characterized by its high aggressiveness, influenced by extracellular matrix (ECM) proteins such as collagen IV and laminin. Creating a cancer microenvironment that mimics these conditions could enhance the clinical relevance of breast cancer models for patient-specific treatments. In this study, a Segmented Organoids with Agile Reassembly (SOAR) printing was established by compartmentalizing TNBC spheroids with ECM proteins (Matrigel®) to simulate varying levels of aggressiveness. Increasing ECM concentration elevated spheroid’s stiffness to approximately 2 kPa, resulting in desmoplasia-like structures and enhanced cancer aggressiveness, as indicated by nuclear pleomorphism, increased Ki-67 expression, and β-catenin translocation. The SOAR-printed TNBC spheroids demonstrated a correlation between increased drug resistance and higher ECM concentrations. Elevated IC₅₀ values and reduced efficacy of doxorubicin, paclitaxel, and cyclophosphamide were observed. This SOAR printing platform effectively captured patient-specific drug responses related to variations in cancer aggressiveness in patient-derived cancer organoids. The SOAR printing facilitates the rapid formation of patient-specific cancer organoids, making it a promising approach for personalized medicine. This versatile strategy offers a robust in vitro cancer model manufacturing platform, with toxicology and drug screening applications.

Statement of significance

Segmented Organoids with Agile Reassembly (SOAR) printing is an innovative biomanufacturing technique that enables rapid and precise construction of 3D organoids. By segmenting and reassembling cancer cells with tailored extracellular matrix (ECM) environments, SOAR can recreate varying levels of tumor aggressiveness more accurately than conventional organoid methods. In this study, we demonstrate that SOAR printing can reliably generate patient-specific cancer organoids directly from biopsy-derived cells. These organoids enable efficient testing of chemotherapy responses, supporting more personalized and effective treatment selection. The scalability and adaptability of SOAR also broaden its impact beyond oncology, offering a versatile platform for high-throughput drug screening, toxicology assessments, and applications in regenerative medicine.
三阴性乳腺癌(TNBC)占乳腺癌病例的10-15%,其特点是高侵袭性,受细胞外基质(ECM)蛋白(如胶原IV和层粘连蛋白)的影响。创建一个模拟这些条件的癌症微环境可以增强乳腺癌模型对患者特异性治疗的临床相关性。在这项研究中,通过将TNBC球体与ECM蛋白(Matrigel®)区分开来模拟不同程度的侵袭性,建立了具有敏捷重组(SOAR)打印的分段类器官。随着ECM浓度的增加,球体的硬度升高至约2 kPa,导致细胞间质样结构和肿瘤侵袭性增强,如核多形性、Ki-67表达增加和β-catenin易位所示。soar打印的TNBC球体显示出耐药性增加与ECM浓度升高之间的相关性。观察到IC₅0值升高,阿霉素,紫杉醇和环磷酰胺的功效降低。这个SOAR打印平台有效地捕获了患者衍生的癌症类器官中与癌症侵袭性变化相关的患者特异性药物反应。SOAR打印促进了患者特异性癌症类器官的快速形成,使其成为个性化医疗的一种有前途的方法。这种多用途的策略提供了一个强大的体外癌症模型制造平台,具有毒理学和药物筛选应用。意义声明:具有敏捷重组(SOAR)打印的分段类器官是一种创新的生物制造技术,可以快速精确地构建3D类器官。通过在定制的细胞外基质(ECM)环境中分割和重组癌细胞,SOAR可以比传统的类器官方法更准确地重建不同水平的肿瘤侵袭性。在这项研究中,我们证明了SOAR打印可以可靠地直接从活检来源的细胞中生成患者特异性的癌症类器官。这些类器官能够有效地测试化疗反应,支持更个性化和有效的治疗选择。SOAR的可扩展性和适应性也将其影响扩展到肿瘤学之外,为高通量药物筛选、毒理学评估和再生医学应用提供了一个多功能平台。
{"title":"The effect of stiffness on cell behavior and drug resistance in patient-derived breast cancer organoids","authors":"Wonwoo Jeong ,&nbsp;Dongju Kim ,&nbsp;Nadeem Wajih ,&nbsp;Hyun-Wook Kang ,&nbsp;Marissa M. Howard-McNatt ,&nbsp;Konstantinos Votanopoulos ,&nbsp;Shay Soker ,&nbsp;Sang Jin Lee","doi":"10.1016/j.actbio.2025.12.026","DOIUrl":"10.1016/j.actbio.2025.12.026","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) accounts for 10–15 % of breast cancer cases and is characterized by its high aggressiveness, influenced by extracellular matrix (ECM) proteins such as collagen IV and laminin. Creating a cancer microenvironment that mimics these conditions could enhance the clinical relevance of breast cancer models for patient-specific treatments. In this study, a Segmented Organoids with Agile Reassembly (SOAR) printing was established by compartmentalizing TNBC spheroids with ECM proteins (Matrigel®) to simulate varying levels of aggressiveness. Increasing ECM concentration elevated spheroid’s stiffness to approximately 2 kPa, resulting in desmoplasia-like structures and enhanced cancer aggressiveness, as indicated by nuclear pleomorphism, increased Ki-67 expression, and <em>β</em>-catenin translocation. The SOAR-printed TNBC spheroids demonstrated a correlation between increased drug resistance and higher ECM concentrations. Elevated IC₅₀ values and reduced efficacy of doxorubicin, paclitaxel, and cyclophosphamide were observed. This SOAR printing platform effectively captured patient-specific drug responses related to variations in cancer aggressiveness in patient-derived cancer organoids. The SOAR printing facilitates the rapid formation of patient-specific cancer organoids, making it a promising approach for personalized medicine. This versatile strategy offers a robust <em>in vitro</em> cancer model manufacturing platform, with toxicology and drug screening applications.</div></div><div><h3>Statement of significance</h3><div>Segmented Organoids with Agile Reassembly (SOAR) printing is an innovative biomanufacturing technique that enables rapid and precise construction of 3D organoids. By segmenting and reassembling cancer cells with tailored extracellular matrix (ECM) environments, SOAR can recreate varying levels of tumor aggressiveness more accurately than conventional organoid methods. In this study, we demonstrate that SOAR printing can reliably generate patient-specific cancer organoids directly from biopsy-derived cells. These organoids enable efficient testing of chemotherapy responses, supporting more personalized and effective treatment selection. The scalability and adaptability of SOAR also broaden its impact beyond oncology, offering a versatile platform for high-throughput drug screening, toxicology assessments, and applications in regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 27-39"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764175","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
Corrigendum to “Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages” “化学基团依赖的血浆聚合优先引导脂肪干细胞向成骨或软骨谱系分化”的更正。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-06 DOI: 10.1016/j.actbio.2025.11.045
M.F. Griffin , A. Ibrahim , A.M. Seifalian , P.E.M. Butler , D.M. Kalaskar , P. Ferretti
{"title":"Corrigendum to “Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages”","authors":"M.F. Griffin ,&nbsp;A. Ibrahim ,&nbsp;A.M. Seifalian ,&nbsp;P.E.M. Butler ,&nbsp;D.M. Kalaskar ,&nbsp;P. Ferretti","doi":"10.1016/j.actbio.2025.11.045","DOIUrl":"10.1016/j.actbio.2025.11.045","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 640-641"},"PeriodicalIF":9.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702728","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
Corrigendum to “Mitochondria-targeting pseudo-stealthy nanophotosensitizer as a potent immunogenic cell death inducer to unleash the cancer-immunity cycle for melanoma therapy” [Acta Biomaterialia 203 (2025) 535–549] “线粒体靶向伪隐形纳米光敏剂作为一种有效的免疫原性细胞死亡诱导剂,释放黑色素瘤治疗的癌症-免疫周期”的勘误表[Acta biomateralia 203(2025) 535-549]。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-02 DOI: 10.1016/j.actbio.2025.11.029
Kewei Shi , Zichong Ye , Hengyan Zhu , Lulu Ren , Hangxiang Wang
{"title":"Corrigendum to “Mitochondria-targeting pseudo-stealthy nanophotosensitizer as a potent immunogenic cell death inducer to unleash the cancer-immunity cycle for melanoma therapy” [Acta Biomaterialia 203 (2025) 535–549]","authors":"Kewei Shi ,&nbsp;Zichong Ye ,&nbsp;Hengyan Zhu ,&nbsp;Lulu Ren ,&nbsp;Hangxiang Wang","doi":"10.1016/j.actbio.2025.11.029","DOIUrl":"10.1016/j.actbio.2025.11.029","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Page 637"},"PeriodicalIF":9.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662817","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
Ultrastructural viscoelasticity of fibrillar collagen identified by AFM Nano-Rheometry and direct indentation 用AFM纳米流变法和直接压痕法鉴定纤维状胶原的超微结构粘弹性。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-11-28 DOI: 10.1016/j.actbio.2025.11.049
Meisam Asgari , Elahe Mirzarazi , Ryan J. Benavides , Yuri M. Efremov , Robert D. Frisina , Hojatollah Vali , Horacio D. Espinosa
Soft tissues exhibit predominantly time-dependent mechanical behavior critical for their biological function in organs like the lungs and aorta, as they can deform and stretch at varying rates depending on their function. Collagen type I serves as the primary structural component in these tissues. The viscoelastic characteristics of such tissues, stemming from diverse energy dissipation mechanisms across various length scales, remains poorly characterized at the nanoscale. Prior experimental investigations have predominantly centered on analyzing tissue responses largely attributed to interactions between cells and fibers. Despite many studies on tissue viscoelasticity from scaffolds to single collagen fibrils, the time-dependent mechanics of collagen fibrils at the sub-fibrillar level remain poorly understood. This pioneering study employs atomic force microscopy (AFM) nano-rheometry and indentation testing to examine the viscoelastic characteristics of individual collagen type I fibrils at the ultrastructural level within distinct topographical zones, specifically focusing on gap and overlap regions. Our investigation has unveiled that collagen fibrils display a viscoelastic response that replicates the mechanical behavior of the tissue at the macroscale. Further, our findings suggest a distinct viscoelastic behavior between the gap and overlap regions, likely stemming from variances in molecular organization and cross-linking modalities within these specific sites. The results of our investigation provide unequivocal proof of the temporal dependence of mechanical properties and provides unique data to be compared to atomistic models, laying a foundation for refining the precision of macroscale models that strive to capture tissue viscoelasticity across varying length scales.

Statement of significance

Soft tissues such as the lungs and aorta depend on collagen to stretch and perform their functions, which involve continuous and dynamic deformation. Although these tissues are known to exhibit viscoelastic behavior, the mechanisms behind this at the fine scale of individual collagen fibril ultrastructure are not well understood. In this study, we used AFM nano-rheometry and direct indentation to be the first to directly measure the viscoelastic properties of collagen at the ultrastructural level. We discovered that single fibrils show time-dependent behavior similar to that of whole tissues, with distinct mechanical differences between regions likely due to variations in molecular organization and bonding. These insights advance our understanding of tissue mechanics and contribute to more accurate multi-scale modeling.
软组织主要表现出时间依赖的机械行为,这对它们在肺和主动脉等器官中的生物功能至关重要,因为它们可以根据其功能以不同的速度变形和拉伸。I型胶原蛋白是这些组织的主要结构成分。这种组织的粘弹性特性,源于不同长度尺度上的不同能量耗散机制,在纳米尺度上仍然缺乏表征。先前的实验研究主要集中在分析组织反应,很大程度上归因于细胞和纤维之间的相互作用。尽管对从支架到单个胶原原纤维的组织粘弹性进行了许多研究,但对亚纤维水平胶原原纤维的时间依赖性力学仍然知之甚少。这项开创性的研究采用原子力显微镜(AFM)纳米流变学和压痕测试来检查不同地形区域内单个I型胶原原纤维在超微结构水平上的粘弹性特性,特别关注间隙和重叠区域。我们的研究揭示了胶原原纤维显示粘弹性反应,在宏观尺度上复制了组织的机械行为。此外,我们的研究结果表明,在间隙和重叠区域之间存在明显的粘弹性行为,可能源于这些特定位点内分子组织和交联方式的差异。我们的研究结果为机械性能的时间依赖性提供了明确的证据,并提供了与原子模型相比较的独特数据,为改进宏观尺度模型的精度奠定了基础,这些模型力求在不同长度尺度上捕获组织粘弹性。意义说明:软组织如肺和主动脉依赖胶原蛋白拉伸和执行其功能,这涉及持续和动态变形。虽然已知这些组织表现出粘弹性行为,但在单个胶原纤维超微结构的精细尺度上,其背后的机制尚不清楚。在本研究中,我们首次使用AFM纳米流变法和直接压痕法在超微结构水平上直接测量胶原蛋白的粘弹性。我们发现单个原纤维表现出与整个组织相似的时间依赖性行为,由于分子组织和键合的变化,不同区域之间存在明显的机械差异。这些见解促进了我们对组织力学的理解,并有助于更准确的多尺度建模。
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引用次数: 0
Surface tension-driven persistence: How hydrogel interfacial properties regulate fibroblast directional migration 表面张力驱动的持久性:水凝胶界面特性如何调节成纤维细胞的定向迁移。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-11-27 DOI: 10.1016/j.actbio.2025.11.058
Sara Faour , Cyrille Vézy , Régis Déturche , Stéphane Dedieu , Jérome Sohier , Rodolphe Jaffiol
The development of viscoelastic biomaterials with tunable mechanical properties is a key issue in a wide range of applications in mechanobiology. While numerous foregoing works have revealed the impact of bulk matrix stiffness on cellular and multicellular responses, few have examined the effect of interfacial mechanical properties, such as surface tension σ. Owing to the elastocapillarity phenomenon, σ of soft materials can dominate their bulk mechanical properties and thus regulate cellular response. To address this complex issue of mechanotransduction largely overlooked in the literature, this study introduces a new polymer-based hydrogel that provides fine control of σ. This hydrogel is composed of short polyethylene glycol (PEG) elastic units, cross-linked with poly-L-lysine dendrigrafts (DGL). The stiffness and interfacial mechanical properties of this hydrogel are controlled by adjusting the DGL/PEG ratio and mechanically characterized with optical tweezers. This powerful optical technique enables active microrheology and surface micro-indentation to assess, with the same setup, elastic modulus and surface tension. To demonstrate the key impact of σ in mechanotransduction, 2D fibroblast migration experiments are conducted on fibronectin-coated hydrogels. Single-cell trajectories were tracked using epi-fluorescence imaging, and direction and speed autocorrelations were computed and analysed using the ”stick–slip” model. This study highlights, for the first time, that cells can adopt directional persistence migration when surface tension increases.
Statement of Significance: A hydrogel composed of PEG and poly-L-lysine dendrigraft has been developed to tune the surface tension of soft materials designed to mimic biological tissues. This interfacial mechanical property was successfully characterized using optical tweezers, after which the two-dimension directional persistent motion of fibroblasts was studied according to the surface tension of hydrogel.
开发具有可调力学性能的粘弹性生物材料是力学生物学广泛应用的一个关键问题。虽然许多先前的工作已经揭示了体基质刚度对细胞和多细胞响应的影响,但很少有人研究界面力学性能(如表面张力σ)的影响。由于弹性毛细现象的存在,软质材料的σ可以支配其体力学性能,从而调节细胞响应。为了解决这个在文献中被忽视的机械转导的复杂问题,本研究引入了一种新的聚合物基水凝胶,可以很好地控制σ。该水凝胶由短聚乙二醇(PEG)弹性单元组成,与聚l -赖氨酸枝枝(DGL)交联。通过调节DGL/PEG比来控制水凝胶的刚度和界面力学性能,并用光学镊子对其进行了力学表征。这种强大的光学技术使主动微流变学和表面微压痕能够在相同的设置下评估弹性模量和表面张力。为了证明σ在机械转导中的关键作用,我们在纤维连接蛋白包被的水凝胶上进行了二维成纤维细胞迁移实验。利用外显荧光成像技术跟踪单细胞运动轨迹,利用“粘滑”模型计算和分析方向和速度的自相关性。这项研究首次强调,当表面张力增加时,细胞可以采取定向持久性迁移。意义声明:一种由聚乙二醇和聚l -赖氨酸树胶组成的水凝胶已经被开发出来,用于调节模拟生物组织的软材料的表面张力。利用光学镊子成功表征了成纤维细胞的界面力学特性,然后根据水凝胶的表面张力研究了成纤维细胞的二维定向持久运动。
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引用次数: 0
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Acta Biomaterialia
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