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Acta Biomaterialia最新文献

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Layer- and position-specific characterization of the fracture behavior of the small intestine 小肠断裂行为的层位特异性表征。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-08-12 DOI: 10.1016/j.actbio.2026.08.007
Dorina Hasselbeck, Jintian Liu, Stefano Fusco, Tobias Siebert, Markus Böl
In this study, we investigate the mechanical elastic and failure behavior of porcine small intestinal walls (SIWs). In order to comprehensively examine the small intestine (SI) mechanically, all three sections of the SI, the duodenum, jejunum, and ileum, are examined. Single-edge notched tensile (SENT) experiments are performed on the entire wall structure as well as on the individual layers (serosal, muscular, and mucosal layer). In addition, the experiments are carried out in different loading directions (0°, 45°, and 90°) with respect to the tissue orientation. Overall, the elastic mechanical behavior for all regions and all layers is characterized by a typical, exponential, nonlinear behavior in combination with a partially distinct anisotropic behavior, featuring an broad elastic region λmax of 1.1 to 1.7, with corresponding stresses Pe of approximately 2 to 330 kPa. Failure behavior, as characterized by the critical energy release rate GC, exhibits obvious layer dependence. The average GC value of the mucosal layer is approximately four times higher than that of the muscular layer (1–2 N/mm), while the serosal layer has the highest values, reaching 6–10 N/mm. Additionally, the fracture behavior of the combined muscular and serosal layers of the duodenum, jejunum and ileum can be explained by classical laminate theory. However, the results of the entire wall indicate complicated interlayer behavior between the mucosal and muscular layers. Furthermore, the crack-tip tracking method and local deformation obtained from optical measurements help achieve a clearer understanding of crack initiation and propagation. These results provide a comprehensive dataset about the failure characteristics of the SI that can be used as input or for validating failure models in the future.
Statement of Significance: This study is the first to report on experiments involving the failure of the porcine small intestine. The study investigates the region-, orientation-, and layer-specific mechanical properties of the small intestine in order to gain insight into its behavior under intact and failed conditions. Although layer-specific experimental studies are essential for a comprehensive understanding of small intestine function, they have received little attention to date. Additionally, this study examines crack propagation direction during uniaxial tensile tests. The study provides a unique database that improves our understanding of small intestine failure behavior and serves as a basis for corresponding models.
在这项研究中,我们研究了猪小肠壁(SIWs)的机械弹性和破坏行为。为了全面检查小肠(SI)机械,所有三个部分的小肠,十二指肠,空肠和回肠,进行检查。在整个壁结构以及单个层(浆膜、肌层和粘膜层)上进行单边缘缺口拉伸(SENT)实验。此外,实验在不同的加载方向(0°,45°和90°)相对于组织取向进行。总体而言,所有区域和所有层的弹性力学行为都具有典型的指数非线性行为和部分不同的各向异性行为,其弹性区域λmax为1.1 ~ 1.7,相应的应力Pe约为2 ~ 330 kPa。破坏行为表现出明显的层依赖性,以临界能量释放率GC为特征。粘膜层的平均GC值约为肌肉层的4倍(1-2 N/mm),浆膜层的GC值最高,可达6-10 N/mm。此外,十二指肠、空肠和回肠的肌肉和浆膜结合层的断裂行为可以用经典的层压理论来解释。然而,整个肠壁的结果表明,在粘膜和肌肉层之间存在复杂的层间行为。此外,裂纹尖端跟踪方法和光学测量获得的局部变形有助于更清楚地了解裂纹的起裂和扩展。这些结果提供了一个关于SI失效特征的综合数据集,可以用作输入或用于验证未来的失效模型。意义声明:本研究首次报道了涉及猪小肠衰竭的实验。该研究调查了小肠的区域、方向和层特异性力学特性,以便深入了解其在完好和失效条件下的行为。尽管针对不同肠层的实验研究对于全面了解小肠功能至关重要,但迄今为止,这些研究很少受到关注。此外,本研究还考察了单轴拉伸试验中裂纹的扩展方向。该研究提供了一个独特的数据库,提高了我们对小肠衰竭行为的理解,并为相应的模型提供了基础。
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引用次数: 0
In situ synthesis of a zeolitic imidazolate framework coating on a Mg surface for pH-sensitive drug release 用于ph敏感药物释放的镁表面咪唑酸沸石骨架涂层的原位合成。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-07-31 DOI: 10.1016/j.actbio.2026.07.059
Xia Li, Hongyan Wang, Di Mei, Xinyuan Wang, Lan Chen, Lingchuang Bai, Liguo Wang, Shijie Zhu, Shaokang Guan
Mg alloys have become a new generation of biodegradable medical materials due to their good biocompatibility. However, their rapid corrosion rate in physiological environments and the mismatch between their degradation rate and tissue reconstruction pose challenges for clinical applications. To improve the corrosion resistance and biocompatibility of Mg alloys, drug-loaded corrosion resistant coating has gradually become a research hotspot. In this work, a uniform pH-responsive ZIF-14 coating was in situ synthesized on the surface of Mg alloy via a solvothermal method. Using rapamycin, an anti-restenosis drug, as a model compound, the drug release behavior and biocompatibility of the rapamycin-loaded ZIF-14 coating were evaluated under different pH conditions. ZIF-14 coating exhibited rapid drug release under both acidic and alkaline conditions. The rapamycin-loaded ZIF-14 coating effectively inhibited the excessive proliferation of smooth muscle cells, thereby preventing vascular restenosis after device implantation. Notably, theoretical calculations and experimental characterizations revealed that Zn2+ ions in ZIF-14 precursor solution can coordinate with both imidazole ligands and Mg from the substrate, leading to the formation of a stable ZIF precursor on Mg surface. In addition, ZIF-14 coating enhanced the corrosion resistance of Mg alloy, effectively prolonging its service life. This work provides a new strategy for the design of multifunctional smart coatings on Mg alloy surfaces and shows great potential for applications in biomedical Mg alloy implants.

Statement of significance

This study presents a significant advancement in addressing the limitations of biodegradable Mg alloy stents by developing a uniform, and pH-responsive ZIF-14 coating via one-step in situ solvothermal synthesis. Integrating DFT calculations with experimental validation, this research elucidates the intricate coordination mechanism among Zn2+, imidazole ligands, and Mg, offering fundamental insights into MOFs growth on reactive metal surfaces. This coating exhibits dual-trigger pH-responsive drug release, accelerating drug release under both acidic (local inflammation) and alkaline (Mg corrosion) conditions, thus providing a smart solution for localized therapeutic intervention. Furthermore, this nanostructured coating enhances the corrosion resistance and biocompatibility of Mg alloy. This work proposes a strategy for designing multifunctional smart coatings on biodegradable implants, holding potential for biodegradable implants.
镁合金具有良好的生物相容性,已成为新一代可生物降解的医用材料。然而,它们在生理环境中的快速腐蚀速度以及降解速度与组织重建之间的不匹配为临床应用带来了挑战。为了提高镁合金的耐蚀性和生物相容性,载药耐蚀涂层逐渐成为研究热点。本文采用溶剂热法在镁合金表面原位合成了均匀的ph响应ZIF-14涂层。以抗再狭窄药物雷帕霉素为模型化合物,考察了不同pH条件下负载雷帕霉素的ZIF-14包被的释药行为和生物相容性。ZIF-14涂层在酸性和碱性条件下均表现出快速的药物释放。负载雷帕霉素的ZIF-14包被有效抑制了平滑肌细胞的过度增殖,从而防止器械植入后血管再狭窄。值得注意的是,理论计算和实验表征表明,ZIF-14前驱体溶液中的Zn2+离子可以与咪唑配体和底物中的Mg配合,从而在Mg表面形成稳定的ZIF前驱体。此外,ZIF-14涂层增强了镁合金的耐腐蚀性,有效延长了镁合金的使用寿命。本研究为镁合金表面多功能智能涂层的设计提供了一种新的策略,在生物医学镁合金植入物中显示出巨大的应用潜力。意义声明:本研究通过一步原位溶剂热合成方法开发了一种均匀且ph响应的ZIF-14涂层,在解决可生物降解镁合金支架的局限性方面取得了重大进展。结合DFT计算和实验验证,本研究阐明了Zn2+、咪唑配体和Mg之间复杂的配位机制,为mof在活性金属表面的生长提供了基础见解。该涂层具有双触发ph响应药物释放,在酸性(局部炎症)和碱性(Mg腐蚀)条件下加速药物释放,从而为局部治疗干预提供了一种智能解决方案。此外,该纳米涂层还增强了镁合金的耐腐蚀性和生物相容性。本研究提出了在生物可降解植入物上设计多功能智能涂层的策略,具有生物可降解植入物的潜力。
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引用次数: 0
Hierarchical structures in mammalian enamel from synchrotron X-ray computed tomography 从同步加速器x射线计算机断层扫描观察哺乳动物牙釉质的层次结构。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-07-30 DOI: 10.1016/j.actbio.2026.07.055
Donna Post Guillen, Gabriel Thompson, Zherui Guo, Jack R. Grimm, Cameron Renteria, Dula Parkinson, Viktor Nikitin, Bradley D. Huddleston, Carli Marsico, Dwayne Arola
Many natural and biological materials exhibit intricate hierarchical architectures to effectively manage crack propagation and fracture. This enables them to overcome the critical trade-off between strength and toughness that plagues modern ceramics and ceramic composites. This study investigates the microstructure of enamel from five different mammalian species to inform the synthesis of strong, fracture-resistant bioinspired materials. Dental enamel, the hard, outer surface layer of teeth, is renowned for its exceptional damage tolerance and high strength. Enamel can withstand cracks and other forms of structural damage without leading to catastrophic failure, a property that conventional ceramics often lack. The primary factor contributing to enamel's crack resistance, often attributed to its complex hierarchical microstructure, is the decussation of enamel rods. In this study, synchrotron micro X-ray tomography was performed to elucidate the microstructural assembly of the rods and to characterize the decussation bands. This analysis was conducted across samples taken from different teeth (molar, premolar, canine), tooth regions (cervical, mid-cervical, cusp, intercuspal), and species (lion, wolf, wild African dog, snow leopard, and black bear). Microtomography images were reconstructed and analyzed using a particle image velocimetry technique to offer detailed insights into the decussation bands and the orientation of rods within these bands. Overall, the decussation patterns exhibit branching of the decussation bands reminiscent of Turing patterns, and these organizational motifs within enamel architecture provide a mechanistic perspective on hierarchical structure and its role in damage tolerance.

Statement of significance

This study explores the intricate microstructure of dental enamel from various mammalian species using synchrotron X-ray nano- and microtomography. Through a detailed examination of the enamel rods and their distinct Turing patterns, this new insight offers the potential to unlock the secrets behind enamel's extraordinary strength and unparalleled fracture resistance. Our findings suggest that these patterns help distribute stress and prevent catastrophic failure, offering insights that could inspire the design of advanced, damage-resistant ceramics. This research bridges biology and materials science, potentially leading to the development of innovative materials with applications in extreme environments, such as aerospace and nuclear reactors.
许多天然和生物材料表现出复杂的层次结构,以有效地管理裂纹扩展和断裂。这使他们能够克服困扰现代陶瓷和陶瓷复合材料的强度和韧性之间的关键权衡。本研究调查了五种不同哺乳动物牙釉质的微观结构,为合成强、抗断裂的生物激发材料提供信息。牙釉质是牙齿坚硬的外表层,以其特殊的损伤容忍度和高强度而闻名。搪瓷可以承受裂缝和其他形式的结构损坏,而不会导致灾难性的破坏,这是传统陶瓷通常缺乏的特性。牙釉质抗裂性的主要因素是牙釉质棒的讨论,这通常归因于其复杂的分层微观结构。在这项研究中,进行了同步加速器微x射线断层扫描,以阐明杆的微观结构组装和表征讨论带。该分析是在不同牙齿(臼齿、前臼齿、犬齿)、牙齿区域(颈椎、中颈椎、尖牙、尖间)和物种(狮子、狼、野生非洲狗、雪豹和黑熊)的样本中进行的。显微断层扫描图像重建和分析使用粒子图像测速技术,以提供详细的见解,讨论带和这些波段内的杆的方向。总的来说,讨论模式表现出与图灵模式相似的讨论带分支,这些珐琅结构中的组织图案为层次结构及其在损伤容忍度中的作用提供了一个机械的视角。意义声明:本研究利用同步加速器x射线纳米和显微断层扫描技术探索了不同哺乳动物牙釉质的复杂微观结构。通过对牙釉质棒及其独特的图灵图案的详细检查,这一新的见解为揭开牙釉质非凡的强度和无与伦比的抗断裂性背后的秘密提供了可能。我们的研究结果表明,这些模式有助于分散压力,防止灾难性的失败,为设计先进的抗损伤陶瓷提供了启发。这项研究是生物学和材料科学的桥梁,有可能导致在极端环境中应用的创新材料的发展,如航空航天和核反应堆。
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引用次数: 0
Bioactive glasses as reactive biomaterials: Dissolution-driven structure–function relationships and predictive modelling 作为反应性生物材料的生物活性玻璃:溶解驱动的结构-功能关系和预测模型。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-08-06 DOI: 10.1016/j.actbio.2026.08.005
Amirhossein Moghanian, Ahmet Akif Kizilkurtlu, Arang Pazhouheshgar, Mohammad Nasr Esfahani, Ali Akpek, Danijela Marovic, Sirus Safaee, Håvard J. Haugen
Bioactive glasses (BGs) are reactive biomaterials whose biological effects arise from dissolution: ion exchange, pH evolution, surface-layer formation and calcium phosphate precipitation. Their performance is therefore shaped not by nominal composition alone, but by glass structure, processing, crystallinity, surface area, form factor, medium and test protocol. This critical narrative review reframes BG bioactivity as a time-resolved structure–dissolution–function problem and examines which predictive claims are currently justified. We distinguish direct BG evidence from mechanistically relevant non-BG glass studies and modelling examples from adjacent fields. We discuss how network connectivity, Qⁿ speciation, phosphate and borate structure, modifier identity, structural heterogeneity and accessible surface area govern ion release, pH, surface-layer evolution and mineralisation. Silicate, borate/borosilicate, phosphate-based and sol–gel/mesoporous systems are compared as distinct dissolution programmes rather than fixed bioactivity labels. Atomistic simulations are considered useful sources of structural descriptors when checked against experimental dissolution and biological data. Across these systems, ion-release profiles, pH and supersaturation trajectories, mineralisation kinetics, cytocompatibility windows, antimicrobial or angiogenic cues and mechanical retention can only be interpreted when exposure protocols are reported. Current modelling evidence is strongest for physicochemical outputs, particularly dissolution and ion release under defined conditions. Predicting pH, mineralisation, and cell response requires measured exposure variables, biological metadata, and external validation; in vivo performance remains indirect without paired datasets. We conclude that progress depends less on more complex models than on better-reported experiments, clear uncertainty and cautious claim boundaries.

Statement of significance

Bioactive glass studies often focus on whether apatite forms in simulated body fluid. This review argues that such a binary label misses the central biology: glass structure, processing, surface area and test protocol define dissolution, ion release, pH, surface-layer evolution and the exposure experienced by cells and tissues. We bring together dissolution mechanisms, bioactive glass systems, and predictive modelling within an evidence hierarchy that separates direct bioactive glass data from related glass studies and broader modelling examples. The review clarifies which predictions are currently reliable, which need better datasets, and which remain premature. It offers practical guidance on reporting and validation so that modelling can help prioritise experiments without replacing biological testing or overstating in vivo relevance.
生物活性玻璃(BGs)是一种活性生物材料,其生物效应产生于溶解:离子交换、pH演化、表面层形成和磷酸钙沉淀。因此,它们的性能不仅取决于名义成分,还取决于玻璃结构、加工、结晶度、表面积、形状因子、介质和测试方案。这篇批判性的叙述性综述将BG生物活性重新定义为一个时间解决的结构-溶解-功能问题,并检查了哪些预测性声明目前是合理的。我们将直接的BG证据与机械相关的非BG玻璃研究和邻近领域的建模例子区分开来。我们讨论了网络连通性、Q形态、磷酸盐和硼酸盐结构、改性剂特性、结构非均质性和可达表面积如何影响离子释放、pH、表面层演化和矿化。硅酸盐、硼酸盐/硼硅酸盐、磷酸盐基和溶胶-凝胶/介孔体系作为不同的溶解方案进行比较,而不是固定的生物活性标签。当与实验溶解和生物数据核对时,原子模拟被认为是结构描述符的有用来源。在这些系统中,离子释放谱、pH值和过饱和轨迹、矿化动力学、细胞相容性窗口、抗菌或血管生成线索和机械保留只有在暴露方案报告时才能解释。目前的模拟证据对于物理化学输出,特别是在规定条件下的溶解和离子释放是最强的。预测pH值、矿化和细胞反应需要测量暴露变量、生物元数据和外部验证;在没有配对数据集的情况下,体内性能仍然是间接的。我们的结论是,进步更多地依赖于更好的实验报告、明确的不确定性和谨慎的主张边界,而不是更复杂的模型。意义说明:生物活性玻璃的研究通常集中在磷灰石是否在模拟体液中形成。这篇综述认为,这样的二元标签错过了核心生物学:玻璃结构,加工,表面积和测试方案定义溶解,离子释放,pH,表面层演变和细胞和组织所经历的暴露。我们将溶解机制、生物活性玻璃系统和预测模型纳入证据层次,将直接生物活性玻璃数据与相关玻璃研究和更广泛的建模示例分开。该综述澄清了哪些预测目前是可靠的,哪些需要更好的数据集,哪些仍不成熟。它提供了关于报告和验证的实用指导,因此建模可以帮助确定实验的优先顺序,而不会取代生物测试或夸大体内相关性。
{"title":"Bioactive glasses as reactive biomaterials: Dissolution-driven structure–function relationships and predictive modelling","authors":"Amirhossein Moghanian,&nbsp;Ahmet Akif Kizilkurtlu,&nbsp;Arang Pazhouheshgar,&nbsp;Mohammad Nasr Esfahani,&nbsp;Ali Akpek,&nbsp;Danijela Marovic,&nbsp;Sirus Safaee,&nbsp;Håvard J. Haugen","doi":"10.1016/j.actbio.2026.08.005","DOIUrl":"10.1016/j.actbio.2026.08.005","url":null,"abstract":"<div><div>Bioactive glasses (BGs) are reactive biomaterials whose biological effects arise from dissolution: ion exchange, pH evolution, surface-layer formation and calcium phosphate precipitation. Their performance is therefore shaped not by nominal composition alone, but by glass structure, processing, crystallinity, surface area, form factor, medium and test protocol. This critical narrative review reframes BG bioactivity as a time-resolved structure–dissolution–function problem and examines which predictive claims are currently justified. We distinguish direct BG evidence from mechanistically relevant non-BG glass studies and modelling examples from adjacent fields. We discuss how network connectivity, Qⁿ speciation, phosphate and borate structure, modifier identity, structural heterogeneity and accessible surface area govern ion release, pH, surface-layer evolution and mineralisation. Silicate, borate/borosilicate, phosphate-based and sol–gel/mesoporous systems are compared as distinct dissolution programmes rather than fixed bioactivity labels. Atomistic simulations are considered useful sources of structural descriptors when checked against experimental dissolution and biological data. Across these systems, ion-release profiles, pH and supersaturation trajectories, mineralisation kinetics, cytocompatibility windows, antimicrobial or angiogenic cues and mechanical retention can only be interpreted when exposure protocols are reported. Current modelling evidence is strongest for physicochemical outputs, particularly dissolution and ion release under defined conditions. Predicting pH, mineralisation, and cell response requires measured exposure variables, biological metadata, and external validation; in vivo performance remains indirect without paired datasets. We conclude that progress depends less on more complex models than on better-reported experiments, clear uncertainty and cautious claim boundaries.</div></div><div><h3>Statement of significance</h3><div>Bioactive glass studies often focus on whether apatite forms in simulated body fluid. This review argues that such a binary label misses the central biology: glass structure, processing, surface area and test protocol define dissolution, ion release, pH, surface-layer evolution and the exposure experienced by cells and tissues. We bring together dissolution mechanisms, bioactive glass systems, and predictive modelling within an evidence hierarchy that separates direct bioactive glass data from related glass studies and broader modelling examples. The review clarifies which predictions are currently reliable, which need better datasets, and which remain premature. It offers practical guidance on reporting and validation so that modelling can help prioritise experiments without replacing biological testing or overstating in vivo relevance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 110-124"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Architectural and geometric defects govern distinct load-transfer mechanisms in the meniscus 结构和几何缺陷支配着半月板不同的载荷传递机制。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-08-05 DOI: 10.1016/j.actbio.2026.08.002
Adi Aharonov, Smadar Elinor Sharon, Yana Portnov, Mirit Sharabi
Mechanical disruption in fibrous tissues can arise either from geometric defects that introduce structural discontinuities or from architectural alterations that modify internal load-sharing networks. The mechanical distinction between these mechanisms remains poorly understood in the meniscus. Here, we combined experimental testing of fiber-reinforced biocomposite laminates with finite element (FE) modeling of the medial meniscus to investigate how fibers oriented perpendicular to the primary loading direction regulate deformation and load redistribution. Alginate–silk fibroin laminates with controlled transverse fiber depletion (FD) were tested under uniaxial tension, while complementary FE models incorporated region-specific depletion of radial fibers within the medial meniscus under compressive loading. In the laminates, transverse FD reduced tensile modulus and increased ultimate strain, while ultimate tensile strength remained largely unchanged, indicating preserved load-bearing capacity of tensile-aligned fibers despite reduced transverse reinforcement. Analysis of axial–transverse strain coupling revealed enhanced lateral deformation with increasing FD, consistent with reduced inter-fiber constraint. In contrast, notch introduction altered deformation pathways and fiber recruitment, resulting in apparent stiffening and reduced ultimate strain. FE simulations further showed that radial FD does not induce uniform mechanical weakening but instead produces region-dependent redistribution of strain, stress, and tibial contact pressure. Together, these findings demonstrate that architectural fiber disruption and geometric defects govern fundamentally different load-transfer mechanisms, establishing radial fibers as key regulators of deformation coupling rather than primary load-bearing elements.

Statement of significance

Radial fibers are a defining structural feature of meniscal architecture and are increasingly recognized as mechanically important, yet their role in regulating deformation and load redistribution remains incompletely understood. By combining biomimetic composite experiments with finite element modeling of the meniscus, this study demonstrates that radial fibers function primarily as architectural coupling elements that regulate regional deformation and load transfer rather than acting as principal load-bearing components. Selective disruption of radial fiber continuity induces spatially localized redistribution of strain, stress, and tibial contact pressure without uniform mechanical weakening. These findings establish a mechanistic link between microscale fiber disruption and joint-level load redistribution, providing insight into early meniscal degeneration and informing both meniscal repair strategies and the design of biomimetic fibrous materials.
纤维组织的机械破坏可能是由几何缺陷引起的结构不连续,也可能是由改变内部负载分担网络的结构改变引起的。这些机制之间的力学区别在半月板中仍然知之甚少。在这里,我们将纤维增强生物复合材料层合板的实验测试与内侧半月板的有限元建模相结合,研究垂直于主要加载方向的纤维如何调节变形和载荷再分配。在单轴拉伸下测试了控制横向纤维损耗(FD)的藻酸盐-丝素层压板,而补充的FE模型在压缩载荷下纳入了内侧半月板内径向纤维的区域特异性损耗。在层压板中,横向FD降低了拉伸模量,增加了极限应变,而极限抗拉强度基本保持不变,表明尽管横向增强减少,拉伸定向纤维的承载能力仍然保持不变。轴向-横向应变耦合分析显示,随着FD的增加,横向变形增强,与纤维间约束减小一致。相反,缺口的引入改变了变形路径和纤维的补充,导致明显的硬化和降低了极限应变。有限元模拟进一步表明,径向FD不会导致均匀的机械弱化,而是会产生应变、应力和胫骨接触压力的区域依赖性重新分布。总之,这些发现表明,建筑纤维断裂和几何缺陷从根本上控制着不同的载荷传递机制,确立了径向纤维是变形耦合的关键调节因素,而不是主要的承重元素。意义声明:径向纤维是半月板结构的一个决定性的结构特征,并且越来越多地认识到其在机械上的重要性,然而它们在调节变形和负荷再分配中的作用仍然不完全清楚。通过将仿生复合材料实验与半月板的有限元建模相结合,本研究表明径向纤维主要是作为调节区域变形和载荷传递的建筑耦合元件,而不是主要的承重部件。径向纤维连续性的选择性破坏导致应变、应力和胫骨接触压力的空间局部重新分布,而没有均匀的机械弱化。这些发现建立了微尺度纤维断裂和关节水平负荷再分配之间的机制联系,为早期半月板变性提供了见解,并为半月板修复策略和仿生纤维材料的设计提供了信息。
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引用次数: 0
3D printing in ophthalmology: From basic research to clinical transformation 3D打印在眼科:从基础研究到临床转化。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-07-24 DOI: 10.1016/j.actbio.2026.07.038
Zhuotong Wu, Yong Ma, Liyin Wang, Yexin Gu, Min Tang, Wenguo Cui, Xingtao Zhou, Jing Zhao
3D printing is reshaping ophthalmic biomaterials, tissue models, implants, biosensors, and drug-delivery systems, but its clinical value depends on matching each printing strategy to ocular-specific requirements rather than on printing capability alone. This review classifies ophthalmic 3D printing into extrusion-based, inkjet-based, electric field-assisted, and light-assisted approaches, while clarifying the boundary between acellular material inks and cell-laden bioinks. We summarize how ink formulation, spatial resolution, optical transparency, mechanical stiffness, degradation, sterilization, immune response, and regulatory classification influence applications in corneal, conjunctival, lens, retinal, orbital, sensing, and drug-delivery contexts. We further discuss hybrid printing and artificial intelligence (AI)-assisted process control as emerging strategies that may improve patient-specific design, reproducibility, and quality assurance. By emphasizing current limitations, clinical translation barriers, and actionable priorities, this review aims to provide a balanced roadmap from basic ophthalmic 3D-printing research toward clinically meaningful transformation.

Statement of significance

Ophthalmic diseases affect millions worldwide, yet traditional treatments like eye drops suffer from poor efficacy due to the eye's complex biological barriers. Three-dimensional (3D) printing offers a revolutionary solution by enabling the creation of customized, structurally precise biomaterials. This review provides a comprehensive overview of how advanced 3D printing technologies are being used to engineer delicate eye tissues (cornea, conjunctiva, and retina) and develop novel drug delivery systems (microneedles and smart contact lenses). Furthermore, we introduce the concept of 'dynamic bioprinting,' highlighting how smart materials can adapt to the ocular microenvironment over time. This work bridges the gap between biomaterial structure-function design and clinical ophthalmology, providing a roadmap for future personalized vision therapies.
3D打印正在重塑眼科生物材料、组织模型、植入物、生物传感器和药物输送系统,但其临床价值取决于每种打印策略与眼部特定需求的匹配,而不仅仅是打印能力。本文将眼科3D打印分为基于挤压的、基于喷墨的、电场辅助的和光辅助的方法,同时澄清了非细胞材料墨水和细胞负载生物墨水之间的界限。我们总结了油墨配方、空间分辨率、光学透明度、机械刚度、降解、灭菌、免疫反应和调节分类如何影响角膜、结膜、晶状体、视网膜、眼窝、传感和药物传递等领域的应用。我们进一步讨论了混合打印和人工智能(AI)辅助过程控制作为新兴策略,可以改善特定患者的设计,可重复性和质量保证。通过强调当前的局限性、临床翻译障碍和可操作的优先事项,本综述旨在提供一个平衡的路线图,从基础眼科3d打印研究到临床有意义的转化。重要说明:眼病影响着全世界数百万人,但由于眼睛复杂的生物屏障,滴眼液等传统治疗方法效果不佳。三维(3D)打印提供了一种革命性的解决方案,可以创建定制的、结构精确的生物材料。这篇综述全面概述了先进的3D打印技术如何被用于设计精致的眼部组织(角膜、结膜和视网膜)和开发新的药物输送系统(微针和智能隐形眼镜)。此外,我们引入了“动态生物打印”的概念,强调智能材料如何随着时间的推移适应眼部微环境。这项工作弥合了生物材料结构功能设计与临床眼科之间的差距,为未来个性化视力治疗提供了路线图。
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引用次数: 0
Golden vesicular nanoadjuvant-loaded injectable hydrogel for locoregional photothermal-immunotherapy of unresectable glioblastoma 载金囊状纳米佐剂可注射水凝胶用于不可切除胶质母细胞瘤的局部光热免疫治疗。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-07-31 DOI: 10.1016/j.actbio.2026.07.057
Songsong Zhao, Zhiwei Sun, Jingyi Wang, Guang Cai, Jun Cao, Xiaoshuo Zhang, Mingyu Xia, Yan Shi, Wenhai Lin, Zhiyuan Zhong, Fenghua Meng
Glioblastoma (GBM) as the most malicious primary brain tumor is infiltrative and often unresectable, which coupled with a profoundly immunosuppressive tumor microenvironment (TME) lead to a poor prognosis for patients. Here, we developed a golden vesicular nanoadjuvant (Au/TLR3-V) comprising gold nanoclusters and TLR3 agonist poly(I:C), formulated within an injectable hydrogel (Au/TLR3-V@gel) for locoregional photothermal-immunotherapy of large orthotopic GBM. Upon near-infrared (NIR) irradiation, Au/TLR3-V generated a potent photothermal response that induced immunogenic cell death and promoted dendritic cell (DC) activation. In TME‑mimicking systems, Au/TLR3-V pre-treated GL261 cells activated DCs accompanied by the upregulation of T‑cell‑recruiting chemokines. In murine models of advanced orthotopic GBM, a single intratumoral injection of Au/TLR3-V@gel followed by a brief NIR irradiation orchestrated a two-stage therapeutic process: localized thermal ablation of the tumor bulk (physical reduction) and subsequent release of Au/TLR3-V to facilitate DCs’ capture of tumor-derived antigens and subsequently amplify DC activation (biological sweeping). When combined with anti‑CTLA‑4 blockade, this therapy achieved a 33% complete cure rate and established potent systemic anti-GBM immunity. By transforming an unresectable and immunologically "cold" tumor into a locally confined immunogenic "hotspot" using a soft, brain-compliant depot, this work provides a promising locoregional approach for unresectable GBM.

Statement of significance

The treatment of unresectable glioblastoma is limited by the lack of biomaterials that can simultaneously provide safe intracranial retention, local tumor ablation, and immune activation. This study presents a brain-mimetic injectable hydrogel incorporating a golden vesicular nanoadjuvant (Au/TLR3‑V@gel) for locoregional photothermal–immunotherapy. The hydrogel offers mechanical compliance with brain tissue and sustained retention, while the released nanoadjuvant amplifies dendritic cell activation in response to tumor antigens generated by photothermal ablation. By coupling local cytoreduction with immune remodeling and further combination with anti-CTLA-4 blockade, this platform achieves durable survival benefits in orthotopic glioblastoma. These findings establish a promising biomaterials-based strategy for intracranial immunotherapy of unresectable brain tumors.
胶质母细胞瘤(Glioblastoma, GBM)是恶性程度最高的原发性脑肿瘤,具有浸润性,往往不可切除,加之肿瘤微环境(tumor microenvironment, TME)具有深度免疫抑制作用,导致患者预后较差。在这里,我们开发了一种金囊状纳米佐剂(Au/TLR3- v),包括金纳米团簇和TLR3激动剂聚(I:C),在可注射水凝胶(Au/TLR3-V@gel)中配制,用于局部光热免疫治疗大面积原位GBM。在近红外(NIR)照射下,Au/TLR3-V产生了强烈的光热反应,诱导免疫原性细胞死亡并促进树突状细胞(DC)活化。在TME模拟系统中,Au/TLR3-V预处理的GL261细胞激活dc,并伴有T细胞募集趋化因子的上调。在小鼠晚期原位GBM模型中,单次瘤内注射Au/TLR3-V@gel,然后进行短暂的近红外照射,协调了两个阶段的治疗过程:肿瘤体积的局部热消融(物理缩小)和随后释放Au/TLR3-V,以促进DC捕获肿瘤来源的抗原,随后放大DC的激活(生物扫描)。当与抗CTLA - 4阻断剂联合使用时,该疗法达到了33%的完全治愈率,并建立了有效的全身抗gbm免疫。通过将不可切除的免疫“冷”肿瘤转化为局部受限的免疫原性“热点”,该研究为不可切除的GBM提供了一种有前途的局部方法。意义声明:不可切除的胶质母细胞瘤的治疗受到缺乏生物材料的限制,这些生物材料可以同时提供安全的颅内保留、局部肿瘤消融和免疫激活。本研究提出了一种含有金色囊状纳米佐剂(Au/TLR3‑V@gel)的脑模拟注射水凝胶,用于局部光热免疫治疗。水凝胶提供了与脑组织的机械顺应性和持续的保留,而释放的纳米佐剂则增强了树突状细胞对光热消融产生的肿瘤抗原的激活。通过将局部细胞减少与免疫重塑结合,并进一步联合抗ctla -4阻断,该平台在原位胶质母细胞瘤中获得持久的生存益处。这些发现为不可切除脑肿瘤的颅内免疫治疗建立了一个有前途的基于生物材料的策略。
{"title":"Golden vesicular nanoadjuvant-loaded injectable hydrogel for locoregional photothermal-immunotherapy of unresectable glioblastoma","authors":"Songsong Zhao,&nbsp;Zhiwei Sun,&nbsp;Jingyi Wang,&nbsp;Guang Cai,&nbsp;Jun Cao,&nbsp;Xiaoshuo Zhang,&nbsp;Mingyu Xia,&nbsp;Yan Shi,&nbsp;Wenhai Lin,&nbsp;Zhiyuan Zhong,&nbsp;Fenghua Meng","doi":"10.1016/j.actbio.2026.07.057","DOIUrl":"10.1016/j.actbio.2026.07.057","url":null,"abstract":"<div><div>Glioblastoma (GBM) as the most malicious primary brain tumor is infiltrative and often unresectable, which coupled with a profoundly immunosuppressive tumor microenvironment (TME) lead to a poor prognosis for patients. Here, we developed a golden vesicular nanoadjuvant (Au/TLR3-V) comprising gold nanoclusters and TLR3 agonist poly(I:C), formulated within an injectable hydrogel (Au/TLR3-V@gel) for locoregional photothermal-immunotherapy of large orthotopic GBM. Upon near-infrared (NIR) irradiation, Au/TLR3-V generated a potent photothermal response that induced immunogenic cell death and promoted dendritic cell (DC) activation. In TME‑mimicking systems, Au/TLR3-V pre-treated GL261 cells activated DCs accompanied by the upregulation of T‑cell‑recruiting chemokines. In murine models of advanced orthotopic GBM, a single intratumoral injection of Au/TLR3-V@gel followed by a brief NIR irradiation orchestrated a two-stage therapeutic process: localized thermal ablation of the tumor bulk (physical reduction) and subsequent release of Au/TLR3-V to facilitate DCs’ capture of tumor-derived antigens and subsequently amplify DC activation (biological sweeping). When combined with anti‑CTLA‑4 blockade, this therapy achieved a 33% complete cure rate and established potent systemic anti-GBM immunity. By transforming an unresectable and immunologically \"cold\" tumor into a locally confined immunogenic \"hotspot\" using a soft, brain-compliant depot, this work provides a promising locoregional approach for unresectable GBM.</div></div><div><h3>Statement of significance</h3><div>The treatment of unresectable glioblastoma is limited by the lack of biomaterials that can simultaneously provide safe intracranial retention, local tumor ablation, and immune activation. This study presents a brain-mimetic injectable hydrogel incorporating a golden vesicular nanoadjuvant (Au/TLR3‑V@gel) for locoregional photothermal–immunotherapy. The hydrogel offers mechanical compliance with brain tissue and sustained retention, while the released nanoadjuvant amplifies dendritic cell activation in response to tumor antigens generated by photothermal ablation. By coupling local cytoreduction with immune remodeling and further combination with anti-CTLA-4 blockade, this platform achieves durable survival benefits in orthotopic glioblastoma. These findings establish a promising biomaterials-based strategy for intracranial immunotherapy of unresectable brain tumors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 476-487"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649868","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
A bioactive intramedullary implant enables accelerated bone regeneration and early load-bearing in distraction osteogenesis 生物活性髓内种植体可以加速骨再生和早期负重牵张成骨。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-07-29 DOI: 10.1016/j.actbio.2026.07.047
Tomohiro Uno, Tien-Ching Lee, Krish Shah, Anthony An-Fa Dahm Chen, Elaine Lui, Hossein Vahid Alizadeh, Jiannan Li, Richard Muniz, Peng Zhao, Andrea Sofía Flores Pérez, Hirotsugu Maekawa, Sungwoo Kim, Masnsen Cherief, Daniel P Regan, Yuya Takakubo, Michiaki Takagi, Aaron James, Jeffrey L. Young, Michael J. Gardner, David G. Mohler, Yunzhi Peter Yang
Distraction osteogenesis (DO) remains limited by prolonged consolidation and delayed bone union. This study evaluated whether a biodegradable, bone morphogenetic protein-2 (BMP-2)-releasing intramedullary implant (IMI) could enhance bone regenerate formation in a rat monofocal femoral lengthening model. We developed a Hybrid Tissue Engineering Construct (HyTEC) comprising a 3D-printed polycaprolactone-β-tricalcium phosphate IMI coated with a BMP-2-loaded hydrogel. Rats underwent standardized lengthening in three groups: control (DO only), IMI (implant without BMP-2), and IMI-BMP2 (BMP-2-releasing implant), with evaluation at postoperative days 31 and 52. The IMI-BMP2 group demonstrated significantly superior osteogenesis, achieving a bone volume fraction of 80 ± 22% at day 31, compared to 35 ± 19% (IMI) and 54 ± 25% (control), indicating accelerated regenerate formation. Radiographic and histological analyses confirmed early, uniform callus formation, while immunohistochemistry revealed elevated osteocalcin expression. Mechanical testing demonstrated restoration of approximately 50% of normal bone strength by day 52. Transcriptomic profiling revealed an exploratory BMP-2-associated regenerative gene signature, suggesting coordinated early-phase regulation of remodeling and metabolic reprogramming. This bioactive implant accelerated bone union, facilitated improved early ambulation consistent with partial mechanical competence restoration, and significantly shortened consolidation time, representing a promising clinically translatable strategy to overcome conventional DO limitations and improve patient outcomes.

Statement of significance

Distraction osteogenesis is an effective strategy for managing large bone defects, but its clinical use is limited by prolonged consolidation and delayed functional recovery. This study presents a biodegradable intramedullary implant that provides sustained bone morphogenetic protein-2 (BMP-2) delivery and markedly accelerates regenerate formation, improves early mechanical strength, and enables earlier weight-bearing in a rat femoral lengthening model. In addition to demonstrating therapeutic efficacy, the work identifies a BMP-2-associated regenerative transcriptional signature linked to remodeling, osteoclast activity, and metabolic reprogramming. These findings establish a clinically translatable biomaterial-based approach to shorten treatment time and improve outcomes in distraction osteogenesis.
牵张成骨(DO)仍然受到长时间实变和延迟骨愈合的限制。本研究评估了可生物降解的骨形态发生蛋白-2 (BMP-2)释放髓内植入物(IMI)是否能在大鼠单灶股骨延长模型中促进骨再生形成。我们开发了一种混合组织工程结构(HyTEC),该结构由3d打印的聚己内酯-β-磷酸三钙IMI包被bmp -2负载的水凝胶组成。三组大鼠进行标准化延长:对照组(仅DO), IMI(不含BMP-2的植入物)和IMI- bmp2(释放BMP-2的植入物),并在术后31和52天进行评估。IMI- bmp2组在成骨方面表现出明显的优势,在第31天达到80±22%的骨体积分数,而IMI组为35±19%,对照组为54±25%,表明再生加速形成。放射学和组织学分析证实早期、均匀的骨痂形成,而免疫组织化学显示骨钙素表达升高。力学测试表明,在第52天恢复了大约50%的正常骨强度。转录组学分析揭示了一个探索性的bmp -2相关的再生基因特征,表明在早期阶段有协调的重塑和代谢重编程调节。这种生物活性植入物加速了骨愈合,促进了与部分机械能力恢复一致的早期活动,并显着缩短了巩固时间,代表了一种有希望的临床可转化策略,可以克服传统的DO限制并改善患者预后。意义声明:牵张成骨术是治疗大面积骨缺损的有效策略,但其临床应用受到长时间巩固和延迟功能恢复的限制。本研究提出了一种可生物降解的髓内植入物,该植入物提供持续的骨形态发生蛋白-2 (BMP-2)递送,并显著加速再生形成,提高早期机械强度,并使大鼠股骨延长模型更早负重。除了证明治疗效果外,该研究还发现了与重塑、破骨细胞活性和代谢重编程相关的bmp -2相关的再生转录特征。这些发现建立了一种临床可翻译的基于生物材料的方法来缩短治疗时间并改善牵张成骨的结果。
{"title":"A bioactive intramedullary implant enables accelerated bone regeneration and early load-bearing in distraction osteogenesis","authors":"Tomohiro Uno,&nbsp;Tien-Ching Lee,&nbsp;Krish Shah,&nbsp;Anthony An-Fa Dahm Chen,&nbsp;Elaine Lui,&nbsp;Hossein Vahid Alizadeh,&nbsp;Jiannan Li,&nbsp;Richard Muniz,&nbsp;Peng Zhao,&nbsp;Andrea Sofía Flores Pérez,&nbsp;Hirotsugu Maekawa,&nbsp;Sungwoo Kim,&nbsp;Masnsen Cherief,&nbsp;Daniel P Regan,&nbsp;Yuya Takakubo,&nbsp;Michiaki Takagi,&nbsp;Aaron James,&nbsp;Jeffrey L. Young,&nbsp;Michael J. Gardner,&nbsp;David G. Mohler,&nbsp;Yunzhi Peter Yang","doi":"10.1016/j.actbio.2026.07.047","DOIUrl":"10.1016/j.actbio.2026.07.047","url":null,"abstract":"<div><div>Distraction osteogenesis (DO) remains limited by prolonged consolidation and delayed bone union. This study evaluated whether a biodegradable, bone morphogenetic protein-2 (BMP-2)-releasing intramedullary implant (IMI) could enhance bone regenerate formation in a rat monofocal femoral lengthening model. We developed a Hybrid Tissue Engineering Construct (HyTEC) comprising a 3D-printed polycaprolactone-β-tricalcium phosphate IMI coated with a BMP-2-loaded hydrogel. Rats underwent standardized lengthening in three groups: control (DO only), IMI (implant without BMP-2), and IMI-BMP2 (BMP-2-releasing implant), with evaluation at postoperative days 31 and 52. The IMI-BMP2 group demonstrated significantly superior osteogenesis, achieving a bone volume fraction of 80 ± 22% at day 31, compared to 35 ± 19% (IMI) and 54 ± 25% (control), indicating accelerated regenerate formation. Radiographic and histological analyses confirmed early, uniform callus formation, while immunohistochemistry revealed elevated osteocalcin expression. Mechanical testing demonstrated restoration of approximately 50% of normal bone strength by day 52. Transcriptomic profiling revealed an exploratory BMP-2-associated regenerative gene signature, suggesting coordinated early-phase regulation of remodeling and metabolic reprogramming. This bioactive implant accelerated bone union, facilitated improved early ambulation consistent with partial mechanical competence restoration, and significantly shortened consolidation time, representing a promising clinically translatable strategy to overcome conventional DO limitations and improve patient outcomes.</div></div><div><h3>Statement of significance</h3><div>Distraction osteogenesis is an effective strategy for managing large bone defects, but its clinical use is limited by prolonged consolidation and delayed functional recovery. This study presents a biodegradable intramedullary implant that provides sustained bone morphogenetic protein-2 (BMP-2) delivery and markedly accelerates regenerate formation, improves early mechanical strength, and enables earlier weight-bearing in a rat femoral lengthening model. In addition to demonstrating therapeutic efficacy, the work identifies a BMP-2-associated regenerative transcriptional signature linked to remodeling, osteoclast activity, and metabolic reprogramming. These findings establish a clinically translatable biomaterial-based approach to shorten treatment time and improve outcomes in distraction osteogenesis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 636-650"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623116","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
ECM-derived biomimetic adhesive patch regulating the inflammatory microenvironment to accelerate oral ulcer healing ecm衍生的仿生贴片调节炎症微环境加速口腔溃疡愈合。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-08-06 DOI: 10.1016/j.actbio.2026.08.004
Qiu-Shuang Cheng, Sheng-Chang Luo, Kai Fan, Zhi-Hong Chen, Jia-Xuan Yang, Jiu-Tao Cao, Bing-Bing Zheng, Zhi-Yuan Lan, Shi-Bin Wang, Pei-Yao Xu, Ai-Zheng Chen
The effective management of oral ulcers is hindered by the constantly moist oral environment and persistently dysregulated inflammatory microenvironment. Inspired by the hierarchical architecture of native mucosa, we engineered a biomimetic bilayer patch to achieve immune modulation and synergistic tissue regeneration. Compositionally mimicking the bioactive lamina propria, the patch features a bioadhesive inner layer enriched with dopamine-modified esophageal mucosa decellularized extracellular matrix (eECM-DA) to specifically recapitulate the native biochemical niche, embedded within hyaluronic acid methacrylate (HAMA) networks loaded with dexamethasone (Dex). Structurally mimicking the protective epithelial barrier, this inner matrix was coupled with a hydrophobic ethylcellulose (EC) backing to shield against saliva erosion. After contact with the moist oral environment, this eECM-DA/HAMA/EC-Dex (EDH/EC-Dex) bilayer patch rapidly contacts the wound and displaces interfacial water to achieve robust wet adhesion. Functionally, the EDH/EC-Dex patch actively reprogrammed the inflammatory milieu in lipopolysaccharide (LPS)-stimulated macrophages by modulating JAK-STAT signaling and antioxidant networks, thereby driving inflammation resolution and promoting orderly regulation of the ulcer microenvironment. In a rat oral ulcer model, EDH/EC-Dex patches demonstrated superior efficacy in accelerating re-epithelialization and functional recovery compared to commercial products. This work introduces an immune-modulatory, ECM-derived platform, offering a promising strategy for oral ulcer management and broader tissue engineering applications.

Statement of significance

A mucosa-inspired bilayer patch is developed for treating oral ulcers. This ECM-derived patch achieves robust wet adhesion and provides a protective barrier against saliva erosion through its bioadhesive inner layer and hydrophobic backing. Mechanistically, it actively regulates JAK-STAT signaling and antioxidant networks, effectively reprogramming the dysregulated inflammatory microenvironment to promote rapid re-epithelialization and functional recovery. This study offers a translatable biomaterial strategy for improving clinical management of oral ulcers.
口腔环境的持续湿润和炎症微环境的持续失调阻碍了口腔溃疡的有效治疗。受天然粘膜分层结构的启发,我们设计了一种仿生双层贴片,以实现免疫调节和协同组织再生。该贴片的组成模仿生物活性固有层,具有生物粘附内层,富含多巴胺修饰的食管黏膜脱细胞外基质(eECM-DA),以特异性地再现天然生化生态位,嵌入含有地塞米松(Dex)的甲基丙烯酸透明质酸(HAMA)网络中。在结构上模仿保护性上皮屏障,这种内部基质与疏水性乙基纤维素(EC)衬底相结合,以防止唾液侵蚀。在与潮湿的口腔环境接触后,这种eECM-DA/HAMA/EC-Dex (EDH/EC-Dex)双层贴片迅速接触伤口并置换界面水,以实现强大的湿粘附。功能上,EDH/EC-Dex贴片通过调节JAK-STAT信号和抗氧化网络,积极地对lps刺激的巨噬细胞中的炎症环境进行重编程,从而推动炎症消退,促进溃疡微环境的有序调节。在大鼠口腔溃疡模型中,与商业产品相比,EDH/EC-Dex贴片在加速再上皮化和功能恢复方面表现出优越的功效。这项工作介绍了一种免疫调节,ecm衍生的平台,为口腔溃疡管理和更广泛的组织工程应用提供了有前途的策略。意义声明:一种粘膜激发的双层贴片被开发用于治疗口腔溃疡。这种ecm衍生的贴片实现了强大的湿粘附,并通过其生物胶粘剂内层和疏水衬底提供了防止唾液侵蚀的保护屏障。在机制上,它积极调节JAK-STAT信号和抗氧化网络,有效地重新编程失调的炎症微环境,以促进快速的再上皮化和功能恢复。本研究为改善口腔溃疡的临床管理提供了一种可翻译的生物材料策略。
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引用次数: 0
Mechanics, Fracture, and Fragmentation of Thrombi: A Computational Study Review 力学、骨折和血栓碎片:一项计算研究综述。
IF 10.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-09-01 Epub Date: 2026-07-27 DOI: 10.1016/j.actbio.2026.07.044
Beikang Gu, Kun Jiang, Taotao Wu, Xianyan Chen, Yanyu Chen, Yang Liu, Kenan Song, He Li, Xianqiao Wang
Thrombosis drives myocardial infarction, acute ischemic stroke and pulmonary embolism, yet more than half of patients undergoing mechanical thrombectomy fail to achieve functional independence, and residual thrombus is detected in up to 91% of cases after catheter-directed thrombolysis. These persistent clinical failures reflect a fundamental gap: thrombus removal is not merely dissolution or extraction, but a multiphysics process governed by the fracture, deformation and fragmentation of a highly anisotropic composite material whose mechanical behavior remains poorly understood and insufficiently predicted. In this review, we examine physics-based and data-driven numerical models of thrombus mechanics, fracture, and fragmentation from a failure-oriented perspective and assess their potential clinical impact. A thrombus is a hierarchically organized composite in which a fibrin network scaffold, functionally differentiated platelet subpopulations and red blood cells interact across scales spanning six orders of magnitude, thus residual thrombus and fragment migration emerge as the fundamental challenges shared by all recanalization strategies from pharmacological thrombolysis to mechanical thrombectomy. We survey six major computational paradigms, including continuum-based approaches, lattice Boltzmann method, particle-based mesoscopic simulation, discrete fiber network models, multiscale coupling frameworks and artificial intelligence/machine learning-assisted methods, and trace the field's evolution over four decades from reaction kinetics to multiphysics fracture coupling. Finally, we delineate critical gaps in current simulation frameworks and argue that AI-driven surrogate models, physics-informed digital twins and generative virtual patient cohorts could transform thrombus simulation from a predominantly academic endeavor into a clinically actionable platform for real-time decision support.

Statement of Significance

Blood clots cause heart attacks, strokes, and pulmonary embolism, yet current treatments fail to fully remove clots in over half of cases. A key reason is that we still cannot predict how clots break apart during treatment. This review is the first to systematically examine thrombus simulation from a mechanical failure perspective, synthesizing six computational paradigms—from continuum mechanics to artificial intelligence—and tracing their four-decade evolution from modeling how clots form to predicting how they fail. By establishing residual thrombus and fragment migration as the shared unresolved challenges across all treatment strategies, we identify critical modeling gaps and propose AI-driven translational pathways, including digital twins and virtual patient cohorts, that could transform clot simulation into a real-time clinical decision-support tool.
血栓形成导致心肌梗死、急性缺血性卒中和肺栓塞,但超过一半的机械取栓患者未能实现功能独立,高达91%的患者在导管溶栓后检测到残留血栓。这些持续的临床失败反映了一个根本的差距:血栓去除不仅仅是溶解或提取,而是一个由高度各向异性复合材料的断裂、变形和破碎所控制的多物理场过程,其力学行为仍然知之甚少,预测不足。在这篇综述中,我们从失败导向的角度研究了基于物理和数据驱动的血栓力学、骨折和碎片的数值模型,并评估了它们的潜在临床影响。血栓是一种分层组织的复合物,其中纤维蛋白网络支架、功能分化的血小板亚群和红细胞在跨越6个数量级的尺度上相互作用,因此残留血栓和碎片迁移成为从药物溶栓到机械取栓的所有再通策略共同面临的基本挑战。我们研究了六种主要的计算范式,包括基于连续体的方法、晶格玻尔兹曼方法、基于粒子的介观模拟、离散光纤网络模型、多尺度耦合框架和人工智能/机器学习辅助方法,并追溯了该领域40多年来从反应动力学到多物理场裂缝耦合的演变。最后,我们描述了当前模拟框架中的关键差距,并认为人工智能驱动的代理模型、物理信息的数字双胞胎和生成虚拟患者队列可以将血栓模拟从主要的学术努力转变为临床可操作的实时决策支持平台。重要意义:血凝块会导致心脏病发作、中风和肺栓塞,但目前的治疗方法在一半以上的病例中不能完全清除血凝块。一个关键的原因是我们仍然无法预测在治疗过程中血栓是如何破裂的。这篇综述首次从机械失效的角度系统地研究了血栓模拟,综合了六种计算范式——从连续介质力学到人工智能——并追踪了它们从建模血栓形成到预测血栓失效的四十年演变。通过将残余血栓和碎片迁移作为所有治疗策略中共同未解决的挑战,我们确定了关键的建模差距,并提出了人工智能驱动的转化途径,包括数字双胞胎和虚拟患者队列,这可以将血块模拟转化为实时临床决策支持工具。
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Acta Biomaterialia
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