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A self-supplying nitric oxide coating on Mg alloy for vascular stents promotes re-endothelialization 血管支架用自供型一氧化氮涂层镁合金促进再内皮化。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-19 DOI: 10.1016/j.actbio.2025.11.033
Zhaoqi Zhang , Hongfei Zhang , Rui Li , Haoran Wu , Shuguang Cao , Liujie Qi , Jingan Li , Shaokang Guan
Mimicking the function of healthy endothelial cells (ECs) to catalyze NO release from endogenous donors represents an effective strategy for repairing the inevitable endothelial injury following stent implantation. However, insufficient levels of endogenous NO donors often limit catalytic NO generation, challenging the maintenance of cardiovascular homeostasis. To address this, a poly(thioctic acid)-arginine (TA-Arg) coating on a fluorinated magnesium (Mg) alloy for in-situ NO supply to address delayed endothelialization. The coating adhered firmly to the MgF2 surface via hydrogen bonding, with TA and Arg connected through salt-bridge hydrogen bond interactions. The immobilized Arg acted as a precursor for NO synthesis, which was catalytically generated in situ by ECs via endothelial nitric oxide synthase (eNOS). Meanwhile, TA served as an eNOS enhancer, boosting intracellular eNOS activity and facilitating the conversion of Arg to NO, enabling sustained and stable localized NO release. In vitro tests showed that the coating significantly decelerated Mg alloy degradation and exhibited high hemocompatibility with pronounced pro-endothelial potential. RNA-seq analyses further revealed that the coating promoted activation of NO-associated PI3K-Akt and MAPK pathways and activated the core antioxidant transcription factor Nrf2 (evidenced by the coordinated upregulation of HMOX1 and NQO1), while concurrently suppressing ferroptosis through genes such as SLC7A11 and FTH1. In vivo implantation confirmed reduced inflammation, enhanced endothelial repair, and inhibited hyperplasia, highlighting the dual role of NO release and antioxidative activity in promoting rapid endothelialization with good biosafety.

Statement of significance

Magnesium (Mg) alloys hold significant promise as next-generation materials for cardiovascular stents owing to their complete biodegradability and excellent biocompatibility. However, their rapid degradation rate and delayed endothelialization remain major obstacles to clinical applications. To address these challenges, this study developed a nitric oxide (NO)-self-supplying poly(thioctic acid)-arginine (TA-Arg) coating on a fluorinated Mg alloy substrate. Both in vitro and in vivo results demonstrated that the TA-Arg sample not only markedly decelerated the degradation of the Mg alloy but also regulated vascular cell behavior, showing considerable potential to promote rapid endothelialization. Overall, this endogenous NO‑supplying strategy is highly straightforward, cost-effective, and scalable, offering a versatile and practical approach for surface modification to facilitate real-world applications of Mg-based stents.
模拟健康内皮细胞(ECs)的功能来催化内源性供体释放NO是修复支架植入术后不可避免的内皮损伤的有效策略。然而,内源性NO供体水平不足往往限制催化NO生成,挑战心血管稳态的维持。为了解决这个问题,在氟化镁(Mg)合金上涂上聚硫辛酸精氨酸(TA-Arg)涂层,用于原位NO供应,以解决延迟内皮化问题。涂层通过氢键牢固地粘附在MgF2表面,TA和Arg通过盐桥氢键相互作用连接。固定化的Arg作为一氧化氮合成的前体,由内皮型一氧化氮合酶(eNOS)在原位催化生成一氧化氮。同时,TA作为eNOS增强剂,提高细胞内eNOS活性,促进Arg向NO的转化,实现持续稳定的局部NO释放。体外实验表明,该涂层显著减缓了镁合金的降解,并表现出高血液相容性,具有明显的促内皮潜能。RNA-seq分析进一步发现,该涂层促进了no相关PI3K-Akt和MAPK通路的激活,激活了核心抗氧化转录因子Nrf2 (HMOX1和NQO1的协同上调证明),同时通过SLC7A11和FTH1等基因抑制铁凋亡。体内植入证实了炎症减轻,内皮修复增强,抑制增生,突出了NO释放和抗氧化活性在促进快速内皮化中的双重作用,具有良好的生物安全性。重要性声明:镁(Mg)合金由于其完全的生物可降解性和优异的生物相容性,作为下一代心血管支架材料具有重要的前景。然而,它们的快速降解率和延迟内皮化仍然是临床应用的主要障碍。为了解决这些挑战,本研究在氟化镁合金基体上开发了一种一氧化氮(NO)-自供应聚硫辛酸-精氨酸(TA-Arg)涂层。体外和体内实验结果表明,TA-Arg样品不仅能显著减缓镁合金的降解,还能调节血管细胞的行为,具有促进快速内皮化的潜力。总的来说,这种内源性NO供应策略非常简单,具有成本效益和可扩展性,为表面改性提供了一种通用和实用的方法,以促进mg基支架的实际应用。
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引用次数: 0
The application of 3D cell culture for melanoma in vitro models 三维细胞培养在黑色素瘤体外模型中的应用。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-21 DOI: 10.1016/j.actbio.2025.11.039
Kailei Xu , Jing Wu , Zehuan Li , Wenjie Chen , Peng Wei , Miaoben Wu
Melanoma remains a formidable clinical challenge due to its high metastatic potential and resistance to conventional therapies, in part reflecting the failure of two-dimensional (2D) culture systems to recapitulate the complex tumor microenvironment (TME). Three-dimensional (3D) cell culture models have emerged as superior platforms over traditional 2D systems for recapitulating the complex TME of melanoma, including native extracellular matrix (ECM) architecture, cell-cell interactions, and biochemical gradients essential for accurate drug screening and mechanistic studies. In this review, we conducted a comprehensive literature survey to classify and critically evaluate melanoma 3D culture platforms into five categories, including melanoma spheroids, biomaterial-encapsulation cultures, melanoma skin equivalents, melanoma-on-chip, and bio-printed melanoma model, focusing on biomaterial composition, architectural fidelity, mechanical properties, and cellular integration, and systematically comparing their advantages and disadvantages. These models have advanced our understanding of melanoma progression, drug resistance mechanisms, cellular behavior, and they offer more reliable platforms for drug screening and development of personalized therapies. Although numerous challenges still need to be tackled, like the current biomaterials seldom replicate the distinct ECM of different skin layers and often neglect the incorporation of immune cells and adipocytes, emerging technologies hold promises for overcoming these challenges by enabling precise fabrication of tissue complexity, incorporation of vasculature, and integration of immune components. These innovations are poised to enhance the physiological relevance of melanoma models, ultimately facilitating the development of more effective treatments and improving patient outcomes.

Statement of significance

Melanoma remains a formidable clinical challenge due to its high metastatic potential and resistance to conventional therapies. 3D cell culture models have emerged as superior platforms over traditional 2D systems for recapitulating the complex TME of melanoma. In this review, we classified melanoma 3D cell culture models into five categories, including melanoma spheroids, biomaterial-encapsulation cultures, melanoma skin equivalents, melanoma-on-chip, and bio-printed melanoma model, focusing on biomaterial composition, architectural fidelity, mechanical properties, and cellular integration, and systematically comparing their benefits and costs. In addition, we also highlighted the challenges of the development on melanoma 3D culture platforms for drug screening and mechanistic studies and discussed the future perspective on the development on melanoma 3D culture platforms.
黑色素瘤仍然是一个巨大的临床挑战,由于其高转移潜力和对传统疗法的耐药性,部分反映了二维(2D)培养系统无法重现复杂的肿瘤微环境(TME)。三维(3D)细胞培养模型已经成为概括黑色素瘤复杂TME的传统二维系统的优越平台,包括天然细胞外基质(ECM)结构、细胞-细胞相互作用以及精确药物筛选和机制研究所必需的生化梯度。在这篇综述中,我们进行了全面的文献调查,将黑色素瘤3D培养平台分为五类,包括黑色素瘤球体、生物材料包封培养、黑色素瘤皮肤等效物、黑素瘤芯片和生物打印黑色素瘤模型,重点关注生物材料组成、建筑保真度、力学性能和细胞整合,并系统地比较了它们的优缺点。这些模型提高了我们对黑色素瘤进展、耐药机制、细胞行为的理解,并为药物筛选和个性化治疗的开发提供了更可靠的平台。尽管仍有许多挑战需要解决,如目前的生物材料很少复制不同皮肤层的不同ECM,并且经常忽略免疫细胞和脂肪细胞的结合,但新兴技术有望通过精确制造组织复杂性,血管系统的结合和免疫成分的整合来克服这些挑战。这些创新将增强黑色素瘤模型的生理学相关性,最终促进更有效治疗的发展,改善患者的预后。意义声明:黑色素瘤由于其高转移潜力和对常规治疗的耐药性,仍然是一个强大的临床挑战。3D细胞培养模型已成为优于传统2D系统的平台,用于再现黑色素瘤的复杂TME。在这篇综述中,我们将黑色素瘤3D细胞培养模型分为五类,包括黑色素瘤球体、生物材料包封培养、黑色素瘤皮肤等效物、黑素瘤芯片和生物打印黑色素瘤模型,重点关注生物材料组成、建筑保真度、机械性能和细胞整合,并系统地比较了它们的收益和成本。此外,我们还强调了黑色素瘤3D培养平台在药物筛选和机制研究方面的发展面临的挑战,并讨论了黑色素瘤3D培养平台的未来发展前景。
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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 : 2026-01-01 Epub 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
Engineered extracellular vesicles as multifunctional therapeutics for restoring periodontal homeostasis 工程细胞外囊泡作为修复牙周稳态的多功能疗法。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-27 DOI: 10.1016/j.actbio.2025.11.060
Junjie Shi , Zongshuai Liu , Jirong Xie , Ze Zhao , Xin Huang , Zhengguo Cao
Periodontal homeostasis refers to the dynamic equilibrium between host defense, microbial control, and tissue remodeling in periodontal tissues. Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues, in which periodontal homeostasis is disturbed. Although many strategies have been developed, treatment of periodontitis and restoration of periodontal homeostasis remain challenging. Extracellular vesicles (EVs) have emerged as a potential cell-free platform for therapeutic applications due to their intrinsic capacity for intercellular communication and biocompatibility. With the advances in engineering, EVs can be functionally tailored to exhibit improved stability, targeting, and bioactivity, attracting increasing attention as regulators for periodontal homeostasis. Accumulating evidence indicates that engineered EVs exert diverse regulatory effects in the periodontal microenvironment, including anti-bacterial activity, anti-inflammatory properties, immunomodulation, antioxidant protection, regulation of programmed cell fate, and promotion of regeneration. Such multifunctional properties enable engineered EVs to address periodontal dysregulation and contribute to the stabilization of tissue homeostasis. This review highlights recent advances in the application of engineered EVs in periodontal research, summarizes their emerging therapeutic roles across these biological domains, and emphasizes their potential as versatile modulators for the maintenance and restoration of periodontal homeostasis.

Statement of significance

This review uniquely integrates recent progress in engineering extracellular vesicles (EVs) with biomaterial-based strategies to restore periodontal homeostasis, a perspective not comprehensively addressed in existing literature. By systematically analyzing approaches such as cargo and surface modification, scaffold incorporation, and artificial vesicle design, it highlights how engineered EVs overcome the limitations of native vesicles and achieve multifunctional regulation of microbial, immune, and regenerative processes. This work provides insights into the convergence of materials science, nanotechnology, and oral biology, and outlines future directions for translating engineered EVs into next-generation therapeutic platforms with broad relevance for biomaterial innovation and regenerative medicine.
牙周内稳态是指牙周组织中宿主防御、微生物控制和组织重塑之间的动态平衡。牙周炎是一种慢性炎症性疾病,其特征是牙周组织被破坏,牙周内平衡被扰乱。尽管已经开发了许多策略,但牙周炎的治疗和牙周稳态的恢复仍然具有挑战性。细胞外囊泡(EVs)由于其内在的细胞间通讯能力和生物相容性,已成为潜在的无细胞治疗应用平台。随着工程技术的进步,电动汽车可以在功能上进行定制,以表现出更好的稳定性、靶向性和生物活性,作为牙周稳态的调节剂越来越受到关注。越来越多的证据表明,工程ev对牙周微环境具有多种调节作用,包括抗菌活性、抗炎特性、免疫调节、抗氧化保护、程序性细胞命运调节和促进再生。这种多功能特性使工程ev能够解决牙周失调并有助于组织稳态的稳定。本文综述了工程化ev在牙周研究中的最新进展,总结了它们在这些生物学领域的新治疗作用,并强调了它们作为维持和恢复牙周稳态的多功能调节剂的潜力。意义声明:本综述独特地整合了工程细胞外囊泡(ev)与基于生物材料的策略来恢复牙周稳态的最新进展,这一观点在现有文献中尚未全面解决。通过系统分析货物和表面修饰、支架结合和人工囊泡设计等方法,重点介绍了工程电动汽车如何克服天然囊泡的局限性,实现微生物、免疫和再生过程的多功能调节。这项工作为材料科学、纳米技术和口腔生物学的融合提供了见解,并概述了将工程电动汽车转化为下一代治疗平台的未来方向,这些平台与生物材料创新和再生医学具有广泛的相关性。
{"title":"Engineered extracellular vesicles as multifunctional therapeutics for restoring periodontal homeostasis","authors":"Junjie Shi ,&nbsp;Zongshuai Liu ,&nbsp;Jirong Xie ,&nbsp;Ze Zhao ,&nbsp;Xin Huang ,&nbsp;Zhengguo Cao","doi":"10.1016/j.actbio.2025.11.060","DOIUrl":"10.1016/j.actbio.2025.11.060","url":null,"abstract":"<div><div>Periodontal homeostasis refers to the dynamic equilibrium between host defense, microbial control, and tissue remodeling in periodontal tissues. Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues, in which periodontal homeostasis is disturbed. Although many strategies have been developed, treatment of periodontitis and restoration of periodontal homeostasis remain challenging. Extracellular vesicles (EVs) have emerged as a potential cell-free platform for therapeutic applications due to their intrinsic capacity for intercellular communication and biocompatibility. With the advances in engineering, EVs can be functionally tailored to exhibit improved stability, targeting, and bioactivity, attracting increasing attention as regulators for periodontal homeostasis. Accumulating evidence indicates that engineered EVs exert diverse regulatory effects in the periodontal microenvironment, including anti-bacterial activity, anti-inflammatory properties, immunomodulation, antioxidant protection, regulation of programmed cell fate, and promotion of regeneration. Such multifunctional properties enable engineered EVs to address periodontal dysregulation and contribute to the stabilization of tissue homeostasis. This review highlights recent advances in the application of engineered EVs in periodontal research, summarizes their emerging therapeutic roles across these biological domains, and emphasizes their potential as versatile modulators for the maintenance and restoration of periodontal homeostasis.</div></div><div><h3>Statement of significance</h3><div>This review uniquely integrates recent progress in engineering extracellular vesicles (EVs) with biomaterial-based strategies to restore periodontal homeostasis, a perspective not comprehensively addressed in existing literature. By systematically analyzing approaches such as cargo and surface modification, scaffold incorporation, and artificial vesicle design, it highlights how engineered EVs overcome the limitations of native vesicles and achieve multifunctional regulation of microbial, immune, and regenerative processes. This work provides insights into the convergence of materials science, nanotechnology, and oral biology, and outlines future directions for translating engineered EVs into next-generation therapeutic platforms with broad relevance for biomaterial innovation and regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 457-480"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643635","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
Effect of stent-graft compliance on hemodynamics and aortic stiffening in an in vivo porcine study 在猪体内研究中,支架移植依从性对血流动力学和主动脉硬化的影响。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-26 DOI: 10.1016/j.actbio.2025.11.051
Ramin Shahbad , Sivapriya Kuniyil , Alexey Kamenskiy , Elizabeth Zermeno , Kaspars Maleckis , Jason MacTaggart , Anastasia Desyatova
<div><div><strong>Background:</strong> Compliance mismatch is a key contributor to adverse vascular remodeling and long-term hemodynamic complications following endovascular aortic repair. However, few in vivo studies have systematically compared the biomechanical and hemodynamic impacts of compliant versus conventional stent-grafts. <strong>Objectives:</strong> In this study, we evaluated an elastomeric nanofibrillar stent-graft (NF-SG) against a commercially available stiff stent-graft (CS-SG) in a swine model, focusing on the effect of stent-graft type on the hemodynamic indices. <strong>Methods:</strong> Twenty Yucatan minipigs were divided into three groups: Control, CS-SG, and NF-SG. The latter two underwent endovascular implantation of the stent-grafts. Hemodynamic assessments were conducted at baseline, immediately post-implantation, and at 18-week follow-up. Local PWV, pressure, pulsatility, distensibility, and harmonic waveform analyses were performed at the ascending and descending thoracic aorta. <strong>Results:</strong> CS-SG implantation led to a significant increase in PWV (from 4.72 to 7.66 m/s), marked reductions in aortic pulsatility at the stented site (from 6.4% to 1.7%), as well as suppressed harmonic contribution (from 39.3% to 29.3%) and distortion (from 0.12 to 0.05), indicating impaired distal impedance regulation. In contrast, the NF-SG preserved baseline PWV (4.69 to 5.37 m/s) and maintained physiological waveform profiles, with minimal changes in harmonic contribution and distortion. NF-SG also showed a smaller reduction in pulsatility at the stented site (from 6.1% to 3.1%). <strong>Conclusions:</strong> These findings demonstrate that NF-SG exhibits superior biomechanical compatibility by preserving aortic compliance and normal hemodynamic function. Compliant stent-grafts may offer a promising strategy to reduce the long-term cardiovascular burden associated with conventional endovascular repairs.</div></div><div><h3>Statement of Significance</h3><div>Compliance mismatch is a significant challenge in endovascular aortic repair, contributing to adverse remodeling and long-term hemodynamic complications. Despite its clinical importance, few in vivo studies have systematically compared the biomechanical and hemodynamic impacts of compliant versus conventional stent-grafts. To address this gap, we performed a longitudinal study in a porcine model, comparing the performance of an innovative elastomeric nanofibrillar stent-graft with that of a commercially available stiff stent-graft. We demonstrate that implantation of the stiff stent-graft led to significant and sustained increases in pulse wave velocity, reduced aortic pulsatility, and impaired distal impedance regulation. In contrast, our elastomeric stent-graft preserved physiological aortic compliance and hemodynamic function, with minimal disruption to harmonic waveform profiles and distal pulsatility. These findings suggest that compliant stent-grafts may offer a
背景:顺应性错配是血管内主动脉修复术后不良血管重构和长期血流动力学并发症的关键因素。然而,很少有体内研究系统地比较了顺应性和传统支架移植物的生物力学和血流动力学影响。目的:在这项研究中,我们在猪模型中评估了弹性纳米纤维支架移植物(NF-SG)和市售的刚性支架移植物(CS-SG),重点研究了支架移植物类型对血流动力学指标的影响。方法:20头尤卡坦迷你猪随机分为对照组、CS-SG组和NF-SG组。后两例接受血管内支架植入术。在基线、植入后立即和18周随访时进行血流动力学评估。在胸升降主动脉处进行局部PWV、压力、脉搏、扩张性和谐波分析。结果:CS-SG植入导致PWV显著增加(从4.72 m/s增加到7.66 m/s),支架部位主动脉搏动明显降低(从6.4%减少到1.7%),谐波贡献(从39.3%减少到29.3%)和失真(从0.12减少到0.05)受到抑制,表明远端阻抗调节受损。相比之下,NF-SG保留了基线PWV(4.69至5.37 m/s)并保持了生理波形剖面,谐波贡献和失真变化最小。NF-SG还显示支架部位的搏动性降低幅度较小(从6.1%降至3.1%)。结论:这些结果表明NF-SG通过保持主动脉顺应性和正常的血流动力学功能,具有良好的生物力学相容性。顺应性支架移植物可能提供了一个有希望的策略,以减少与传统血管内修复相关的长期心血管负担。意义声明:顺应性错配是血管内主动脉修复的重大挑战,会导致不良的重构和长期的血流动力学并发症。尽管具有临床重要性,但很少有体内研究系统地比较了顺应性支架移植与传统支架移植的生物力学和血流动力学影响。为了解决这一差距,我们在猪模型中进行了一项纵向研究,比较了创新的弹性纳米纤维支架移植物与市售的刚性支架移植物的性能。我们证明,植入硬支架导致脉搏波速度显著和持续的增加,主动脉搏动性降低,远端阻抗调节受损。相比之下,我们的弹性支架移植保留了生理主动脉顺应性和血流动力学功能,对谐波波形和远端搏动性的破坏最小。这些发现表明,顺应性支架移植物可能提供了一种有希望的策略,以减少与传统血管内修复相关的长期心血管负担。
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引用次数: 0
Corrigendum to “Repolarization of macrophages to improve sorafenib sensitivity for combination cancer therapy” [Acta Biomaterialia 162 (2023) 98–109] “巨噬细胞复极化提高索拉非尼在联合癌症治疗中的敏感性”的更正[生物材料学报]162(2023)98-109]。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/j.actbio.2025.11.035
Linzhuo Huang , Rui Xu , Weirong Li , Li Lv , Chunhao Lin , Xianzhu Yang , Yandan Yao , Phei Er Saw , Xiaoding Xu
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引用次数: 0
Calcification and structural damage together accelerate porcine pericardium failure 钙化和结构损伤共同加速猪心包衰竭。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-26 DOI: 10.1016/j.actbio.2025.11.046
Luke Guerin , Alix Whelan , Jack O’Leary , Jessica Bagnall , David O’Reilly , Rachel Burke , Evelyn Campbell , Celia Hughes , Emily Growney , Caitríona Lally
Aortic stenosis (AS) is characterised by the narrowing and stiffening of the aortic valve, which restricts blood flow from the heart to the rest of the body. Severe AS is a life-threatening condition which affects 1.48 % of individuals aged 55 and older, with a four-year mortality rate of 44.9 % if left untreated. Minimally invasive treatment for AS involves the implantation of a bioprosthetic valve with porcine or bovine pericardium leaflets, which frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage. The relationship between these two durability-limiting processes is debated, and the influence of device crimping on both factors is not comprehensively understood. This study aims to explore the relationship between calcification and structural damage and determine if device crimping affects these processes. First, porcine pericardium (PP) tissue was exposed to either in vitro calcification in unloaded conditions (calcification) or cyclic bulge loading in saline, without calcification (structural damage). Subsequently, PP was simultaneously calcified and cyclically loaded for 30 million cycles. Simultaneous calcification and loading led to dramatically increased calcification and structural damage, including tissue rupture. Device crimping was not found to have a significant impact on calcification or structural damage. However, fibre architecture was found to affect rupture location, and dramatically affect the rate of rupture of PP. This finding has implications for future bioprosthetic valve leaflet anti-calcification strategies, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification.

Statement of significance

Porcine pericardium (PP) is a commonly used biomaterial, most frequently in the leaflets of bioprosthetic valves. These devices frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage of their leaflets. This work shows that calcification and structural damage work together to accelerate failure of PP, with dramatically increased calcification and structural damage of PP, including rupture, when the tissue is exposed to both simultaneously. Fibre architecture of PP was found to affect rupture location, and dramatically affect rate of rupture. This finding has implications for bioprosthetic leaflet durability, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification and maximise valve durability.
主动脉瓣狭窄(AS)的特征是主动脉瓣变窄和僵硬,这限制了血液从心脏流向身体其他部位。严重AS是一种危及生命的疾病,55岁及以上的患者中有1.48%受到影响,如果不及时治疗,四年死亡率为44.9%。AS的微创治疗包括植入带有猪或牛心包小叶的生物假瓣膜,由于部分由钙化和结构损伤引起的反流或狭窄而经常失败。这两个耐久性限制过程之间的关系是有争议的,并且器件卷曲对这两个因素的影响还没有全面了解。本研究旨在探讨钙化和结构损伤之间的关系,并确定设备卷曲是否影响这些过程。首先,将猪心包(PP)组织暴露在无负荷条件下体外钙化(钙化)或生理盐水中循环膨化(无钙化)。随后,PP同时钙化并循环加载3000万次。同时钙化和负荷导致钙化和结构损伤急剧增加,包括组织破裂。没有发现设备卷曲对钙化或结构损伤有显著影响。然而,研究发现纤维结构会影响破裂位置,并显著影响PP的破裂率。这一发现对未来的生物假体瓣膜小叶抗钙化策略具有重要意义,其中应考虑受潜在组织纤维结构影响的组织力学,以尽量减少结构损伤和钙化。意义说明:猪心包(PP)是一种常用的生物材料,最常用于生物假体瓣膜的小叶。这些装置经常因反流或狭窄而失效,部分原因是其小叶的钙化和结构损伤。这项工作表明,钙化和结构损伤共同作用加速PP的失效,当组织同时暴露于两者时,PP的钙化和结构损伤(包括破裂)急剧增加。聚丙烯的纤维结构影响断裂位置,并显著影响断裂率。这一发现对生物假体小叶耐久性具有重要意义,其中应考虑受底层组织纤维结构影响的组织力学,以最大限度地减少结构损伤和钙化,并最大限度地提高瓣膜耐久性。
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引用次数: 0
A physiological oxygen gradient liver-zonation-on-a-chip reveals HIF-2α intervention in hepatic lipotoxicity 一项生理性氧梯度肝脏分区芯片揭示HIF-2α干预肝脂毒性。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/j.actbio.2025.11.044
Yushen Wang , Xinyu Li , Junlei Han , Feng Kong , Zhipeng Xu , Huili Hu , Li Wang
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disease characterized by lipid zonation, which is closely linked to the functional zonation of liver lobules. However, existing models cannot faithfully replicate the oxygen gradient that regulates liver zonation, hindering a clear understanding of the progression and intervention mechanisms in MASLD. Here, we constructed a MASLD liver-zonation-on-a-chip that utilizes an engineering strategy based on “environmental oxygen convection and diffusion”, achieving a controllable oxygen concentration gradient (3.7 %-8.9 %) that closely mimics the in vivo hepatic microenvironment. This platform successfully recapitulates the typical features and clinicopathological phenotypes of the liver lobule while enabling continuous monitoring of liver injury. We found that upregulation of the oxygen-sensing factor HIF-2α does not directly promote lipid accumulation. Instead, it indirectly facilitates the progression of MASLD by enhancing the transcriptional activity of β-catenin through the WNT signaling pathway (e.g., AXIN2, DVL1). As regulators of the damage process, HIF-2α and β-catenin may be targeted to improve outcomes in MASLD.

Statement of Significance

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common liver disorder characterized by lipid zonation, which is closely related to the functional zonation of liver lobules. However, existing models are unable to accurately replicate the oxygen (O2) gradients that regulate liver zonation, a limitation that hinders their ability to accurately reflect hepatocyte pathophysiology and obstructs understanding of the mechanisms underlying MASLD progression. This study constructs a liver-zonation-on-a-chip with a controllable physiological O₂ gradient and integrated biosensing for non-destructive injury monitoring. The O2 gradient chip successfully replicates liver lobule zonation, providing an engineering approach to overcoming the challenge of low regional heterogeneity in liver organoids. The application of the liver-zonation-on-a-chip in pathological assessments has also been thoroughly evaluated, offering potential solutions for MASLD interventions.
代谢功能障碍相关脂肪变性肝病(MASLD)是一种以脂质分区为特征的常见肝脏疾病,与肝小叶的功能分区密切相关。然而,现有的模型不能忠实地复制调节肝脏分区的氧梯度,阻碍了对MASLD进展和干预机制的清晰理解。在这里,我们构建了一个基于“环境氧对流和扩散”的工程策略的MASLD肝脏分区芯片,实现了一个可控的氧浓度梯度(3.7%-8.9%),接近模拟体内肝脏微环境。该平台成功地概括了肝小叶的典型特征和临床病理表型,同时能够连续监测肝损伤。我们发现,氧敏感因子HIF-2α的上调并不直接促进脂质积累。相反,它通过WNT信号通路(如AXIN2、DVL1)增强β-catenin的转录活性,间接促进MASLD的进展。作为损伤过程的调节因子,HIF-2α和β-catenin可以靶向改善MASLD的预后。声明意义:代谢功能障碍相关脂肪变性肝病(MASLD)是一种以脂质分带为特征的常见肝脏疾病,与肝小叶的功能分带密切相关。然而,现有的模型无法准确地复制调节肝脏分区的氧(O2)梯度,这一限制阻碍了它们准确反映肝细胞病理生理的能力,并阻碍了对MASLD进展机制的理解。本研究构建了一种具有可控生理O₂梯度和集成生物传感的肝脏分区芯片,用于非破坏性损伤监测。O2梯度芯片成功复制肝小叶分区,为克服肝类器官低区域异质性的挑战提供了一种工程方法。肝脏芯片分区在病理评估中的应用也得到了全面的评估,为MASLD干预提供了潜在的解决方案。
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引用次数: 0
A latent TGF-β conjugated scaffold improves neocartilage development 潜在TGF-β共轭支架促进新软骨发育。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-11-20 DOI: 10.1016/j.actbio.2025.11.037
Tianbai Wang , Yifan Peng , Bor-Lin Huang , Enkhjargal Budbazar , Celina C. Maldonado , Andrew Martin , Matthew D. Layne , Joanne E. Murphy-Ullrich , Mark W. Grinstaff , Michael B. Albro
TGF-β is conventionally supplemented in culture medium at supraphysiologic doses to accelerate neocartilage development. While enhancing extracellular matrix (ECM) biosynthesis, supraphysiologic TGF-β further promotes non-hyaline cartilage features, including hyperplasia, hypertrophy, and ECM heterogeneities. In native cartilage, TGF-β is present in a latent complex (LTGF-β), which undergoes cell-mediated activation, leading to moderated, physiologic dosing regimens that avoid detrimental features associated with TGF-β excesses. Here, we explore a bio-inspired strategy, consisting of LTGF-β-conjugated scaffolds, providing TGF-β exposure regimens that are moderated and uniformly administered throughout the construct. We evaluate the performance of LTGF-β scaffolds with bovine chondrocyte-seeded agarose constructs compared to outcomes from active TGF-β media supplementation (MS) at a physiologic 0.3 ng/mL dose (MS-0.3), supraphysiologic 10 ng/mL dose (MS-10), or TGF-β free. LTGF-β scaffolds achieve native-matched mechanical properties and sGAG content, while providing a cell morphology and collagen distribution more reminiscent of hyaline cartilage. LTGF-β scaffolds further afford an optimal chondrogenic phenotype, marked by an up to 28-fold reduction of COL-I and 17-fold reduction of COL-X expression relative to TGF-β-free and MS-10, respectively. Further, LTGF-β scaffolds significantly reduce mechanical and biochemical heterogeneities relative to MS-0.3 and MS-10. Overall, LTGF-β scaffolds improve the composition, structure, material properties, and cell phenotype of neocartilage.

Statement of significance

Inspired by native regulatory mechanisms, we introduce a latent TGF-β conjugated scaffold that enables localized, cell-mediated activation of TGF-β at physiologic levels. This approach yields neocartilage with native-matched composition and mechanical properties, while maintaining a hyaline-cartilage-like cell phenotype and morphology, thus mitigating the adverse developmental features associated with conventional active TGF-β dosing. This bio-inspired platform offers a compelling solution to current TGF-β delivery challenges to improve cartilage regeneration outcomes.
TGF-β通常在培养基中以超生理剂量补充,以加速新软骨的发育。在增强细胞外基质(ECM)生物合成的同时,生理上TGF-β进一步促进非透明软骨特征,包括增生、肥大和ECM异质性。在天然软骨中,TGF-β存在于一种潜伏复合物(LTGF-β)中,LTGF-β经历细胞介导的激活,导致适度的生理性给药方案,避免与TGF-β过量相关的有害特征。在这里,我们探索了一种生物启发策略,包括LTGF-β缀合支架,提供TGF-β暴露方案,在整个构建过程中被调节和统一施用。我们评估了用牛软骨细胞种子琼脂糖构建的LTGF-β支架的性能,并将其与活性TGF-β培养基补充(MS)在生理剂量0.3 ng/mL (MS-0.3)、超生理剂量10 ng/mL (MS-10)或TGF-β游离剂量的结果进行了比较。对于缩小尺寸的结构,LTGF-β支架实现天然匹配的机械性能和sGAG含量,同时提供更让人想起透明软骨的细胞形态和胶原分布。LTGF-β支架进一步提供了最佳的软骨形成表型,与TGF-β无支架和MS-10支架相比,COL-I和COL-X的表达分别减少了28倍和17倍。此外,对于常规大小的结构,LTGF-β支架相对于MS-0.3和MS-10显著降低了机械和生化异质性。总之,LTGF-β支架改善了新软骨的组成、结构、材料性能和细胞表型。意义声明:受天然调节机制的启发,我们引入了一种潜在的TGF-β共轭支架,可以在生理水平上实现局部的、细胞介导的TGF-β激活。这种方法产生的新软骨具有天然匹配的成分和机械性能,同时保持透明软骨样细胞表型和形态,从而减轻与传统活性TGF-β剂量相关的不良发育特征。这种生物启发的平台为当前TGF-β递送挑战提供了令人信服的解决方案,以改善软骨再生结果。
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引用次数: 0
In vitro silicone oil emulsification in retinal detachment treatment: Methods, designs, and future strategies 体外硅油乳化治疗视网膜脱离:方法、设计和未来策略。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 Epub Date: 2025-12-12 DOI: 10.1016/j.actbio.2025.12.024
Natalie Jaklová, Barbora Kamenická
<div><div>Silicone oils are widely used as intraocular tamponade agents in vitreoretinal surgery, particularly in the treatment of complex retinal detachments and other severe posterior segment pathologies such as proliferative diabetic retinopathy, macular holes, ocular trauma, or endophthalmitis. While they offer mechanical support for retinal reattachment, their prolonged intraocular presence is associated with the risk of emulsification, i.e., a process in which the oil phase breaks into subvisible droplets that can obstruct aqueous outflow and compromise visual outcomes. Although emulsification is frequently attributed to interfacial shear stresses generated during ocular motion, especially saccades, the underlying mechanisms remain poorly understood due to the multifactorial nature of the intraocular environment. This review provides a comprehensive analysis of experimental approaches used to investigate silicone oil emulsification, including vortex systems, mechanical shakers, artificial eye chambers, and microfluidic eye-on-a-chip platforms. We critically evaluate the physicochemical and biomechanical parameters influencing droplet formation. Despite significant progress, data from current in vitro models remain heterogeneous and often difficult to compare due to differences in design, fluid composition, and analytical endpoints. Based on the collective evidence, we propose a set of experimental recommendations aimed at emulsification in vitro, including the use of high-molecular-weight modified oils, standardized fluid compositions, advanced eye-mimicking platforms, and improved experimental and analytical protocols. Finally, we highlight the potential of next-generation testing platforms and biocompatible tamponades to offer physiologically relevant, reproducible, and standardized assessment of emulsification resistance. These insights aim to guide the rational design of improved tamponade agents and testing methodologies in future vitreoretinal applications.</div></div><div><h3>Statement of significance</h3><div>Silicone oils are widely used as tamponades in retinal detachment surgery, yet their long-term stability is compromised by emulsification, leading to severe complications such as glaucoma. Although many in vitro studies have attempted to model this process, their findings remain fragmented and often contradictory. This review provides the first systematic, cross-platform analysis of silicone oil emulsification, critically comparing mechanical, chamber-based, and eye-on-a-chip approaches. By identifying unifying trends, methodological gaps, and underexplored parameters such as interfacial rheology and biomechanics, it establishes a roadmap toward standardized, physiologically relevant testing. These insights are significant not only for improving current tamponade materials but also for guiding the design of next-generation biomaterials and experimental platforms at the interface of ophthalmology, biomaterials science, and fluid
硅油在玻璃体视网膜手术中被广泛用作眼内填塞剂,特别是在治疗复杂的视网膜脱离和其他严重的后段病变,如增殖性糖尿病视网膜病变、黄斑孔、眼外伤或眼内炎。虽然它们为视网膜重新附着提供了机械支持,但它们在眼内的长期存在与乳化的风险有关,即油相破裂成不可见的液滴的过程,可以阻碍水流出并影响视力。尽管乳化症经常被认为是由眼内运动(尤其是扫视)过程中产生的界面剪切应力引起的,但由于眼内环境的多因素性质,人们对其潜在机制知之甚少。本文综述了用于研究硅油乳化的实验方法,包括涡旋系统、机械振动器、人工眼室和微流控眼芯片平台。我们批判性地评估影响液滴形成的物理化学和生物力学参数。尽管取得了重大进展,但由于设计、流体成分和分析终点的差异,目前体外模型的数据仍然不均匀,往往难以比较。基于这些证据,我们提出了一套针对体外乳化的实验建议,包括使用高分子量改性油、标准化液体成分、先进的眼模拟平台以及改进的实验和分析方案。最后,我们强调了下一代测试平台和生物相容性填塞的潜力,以提供生理学上相关的、可重复的和标准化的乳化抗性评估。这些见解旨在指导在未来玻璃体视网膜应用中合理设计改进的填塞剂和测试方法。意义声明:硅油在视网膜脱离手术中被广泛用作填塞剂,但其长期稳定性受到乳化的影响,导致严重的并发症,如青光眼。尽管许多体外研究试图模拟这一过程,但他们的发现仍然是零散的,而且往往是相互矛盾的。这篇综述提供了第一个系统的、跨平台的硅油乳化分析,批判性地比较了机械的、基于腔室的和眼上芯片的方法。通过确定统一的趋势、方法上的差距和未充分开发的参数,如界面流变学和生物力学,它建立了标准化的路线图,生理学相关的测试。这些见解不仅对改善现有填塞材料具有重要意义,而且对指导下一代生物材料和实验平台的设计具有重要意义,这些实验平台位于眼科、生物材料科学和流体力学的界面。
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引用次数: 0
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