Bioactive Materials最新文献_第6页

Synergistic mitochondrial homeostasis regulation and cholinergic circuits reconstruction via a one-step synthesized multifunctional hydrogel facilitates spinal cord injury repair 一步合成多功能水凝胶协同线粒体稳态调节和胆碱能回路重建促进脊髓损伤修复

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.009

Yiqian Luo , Pan Jiang , Daoqiang Huang , Hong Li , Jiale He , Ruoqi Shen , Yunheng Jiang , Limin Rong , Bin Liu

Neural Stem Cells (NSCs) possess significant potential to form new neural networks. However, following spinal cord injury (SCI), mitochondrial dysfunction leads to the excessive accumulation of reactive oxygen species (ROS), which severely impairs the neuronal differentiation of endogenous NSCs and thus hinders neural regeneration. Here, we report a multifunctional hydrogel, Poly(LA-Cho)/SS31 (PLCS), synthesized in one step using lipoic acid (LA), choline bicarbonate, and elamipretide (SS31). PLCS hydrogel exhibits injectability, self-healing ability, tissue adhesion, and sequential drug release. Initially, SS31 is released preferentially to scavenge mitochondrial ROS and alleviate mitochondrial dysfunction. Subsequently, LA is continuously to scavenge ROS. Notably, PLCS hydrogel not only promotes NSCs differentiation into cholinergic neurons but also increases acetyl-CoA levels and supplies choline, offering necessary substrates for acetylcholine synthesis in newly formed cholinergic neurons to support their functional maturation. The PLCS hydrogel achieves robust nerve regeneration and significantly improves motor, sensory, and bladder functions in rat models of SCI. RNA sequencing suggests the PI3K-Akt pathway may contribute to spinal cord repair. This one-step synthesis method without catalysts and organic solvents can effectively integrate physical and biological functions of hydrogel, through simple mixing, offering a highly promising strategy for the clinical translation of SCI treatment and other central nervous system injuries.

神经干细胞（NSCs）具有形成新的神经网络的巨大潜力。然而，脊髓损伤（SCI）后，线粒体功能障碍导致活性氧（ROS）过度积累，严重损害内源性NSCs的神经元分化，从而阻碍神经再生。在这里，我们报道了一种多功能水凝胶Poly(LA- cho)/SS31 (PLCS)，它是用硫辛酸（LA）、碳酸氢钠胆碱和埃拉米普肽（SS31）一步合成的。PLCS水凝胶具有可注射性、自愈性、组织黏附性和药物顺序释放性。最初，优先释放SS31清除线粒体ROS，缓解线粒体功能障碍。随后，LA不断清除ROS。值得注意的是，PLCS水凝胶不仅能促进NSCs向胆碱能神经元分化，还能提高乙酰辅酶a水平并提供胆碱，为新形成的胆碱能神经元合成乙酰胆碱提供必要的底物，支持其功能成熟。在脊髓损伤大鼠模型中，PLCS水凝胶实现了强大的神经再生，并显著改善了运动、感觉和膀胱功能。RNA测序表明PI3K-Akt通路可能参与脊髓修复。这种无需催化剂和有机溶剂的一步合成方法，通过简单的混合，可以有效地整合水凝胶的物理和生物功能，为脊髓损伤治疗和其他中枢神经系统损伤的临床翻译提供了一种非常有前景的策略。

{"title":"Synergistic mitochondrial homeostasis regulation and cholinergic circuits reconstruction via a one-step synthesized multifunctional hydrogel facilitates spinal cord injury repair","authors":"Yiqian Luo , Pan Jiang , Daoqiang Huang , Hong Li , Jiale He , Ruoqi Shen , Yunheng Jiang , Limin Rong , Bin Liu","doi":"10.1016/j.bioactmat.2025.12.009","DOIUrl":"10.1016/j.bioactmat.2025.12.009","url":null,"abstract":"<div><div>Neural Stem Cells (NSCs) possess significant potential to form new neural networks. However, following spinal cord injury (SCI), mitochondrial dysfunction leads to the excessive accumulation of reactive oxygen species (ROS), which severely impairs the neuronal differentiation of endogenous NSCs and thus hinders neural regeneration. Here, we report a multifunctional hydrogel, Poly(LA-Cho)/SS31 (PLCS), synthesized in one step using lipoic acid (LA), choline bicarbonate, and elamipretide (SS31). PLCS hydrogel exhibits injectability, self-healing ability, tissue adhesion, and sequential drug release. Initially, SS31 is released preferentially to scavenge mitochondrial ROS and alleviate mitochondrial dysfunction. Subsequently, LA is continuously to scavenge ROS. Notably, PLCS hydrogel not only promotes NSCs differentiation into cholinergic neurons but also increases acetyl-CoA levels and supplies choline, offering necessary substrates for acetylcholine synthesis in newly formed cholinergic neurons to support their functional maturation. The PLCS hydrogel achieves robust nerve regeneration and significantly improves motor, sensory, and bladder functions in rat models of SCI. RNA sequencing suggests the PI3K-Akt pathway may contribute to spinal cord repair. This one-step synthesis method without catalysts and organic solvents can effectively integrate physical and biological functions of hydrogel, through simple mixing, offering a highly promising strategy for the clinical translation of SCI treatment and other central nervous system injuries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 370-395"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881687","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

Antifreezing hydrogels for biomedical applications from design strategies to emerging multifunctionality 从设计策略到新兴的多功能生物医学应用的防冻水凝胶

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.053

Jiang Wu , Lijin Wang , Manhui Zheng , Jie Xu , Zixuan Gong , Boxuan Wu , Huacheng He , Jie Zheng

Antifreezing hydrogels are gaining increasing attention as promising materials for biomedical applications in subzero environments, including cryopreservation, cold-adaptive bioelectronics, wearable sensing, and tissue engineering. Despite recent progress, this is still a relatively underexplored research area, with many fundamental and translational challenges remaining. However, the unique ability of antifreezing hydrogels to sustain flexibility, conductivity, and biological compatibility under freezing conditions underscores their immense potential for future biomedical and engineering innovations. This review provides a targeted overview of the design principles, antifreezing mechanisms, and application-specific adaptations of antifreezing hydrogels. We begin by summarizing fundamental antifreezing strategies, including the incorporation of cryoprotective agents, polymer network engineering, crosslinking architectures, and supramolecular self-healing designs. Particular emphasis is placed on recent advances in hydrogels with integrated strain-sensing, temperature-responsiveness, and multifunctional biosensing capabilities under extreme cold conditions. We then examine cryopreservation-oriented hydrogels, highlighting their ability to suppress ice nucleation, minimize intracellular ice formation, and preserve biological function. The review also explores hydrogel-based cold-adaptive bioelectronics, including low-temperature wearable sensors, flexible circuits, and self-powered interfaces. Finally, we discuss key considerations for clinical translation, such as biocompatibility, degradability, and long-term stability. By linking molecular design to macroscopic performance, this review aims to establish a forward-looking framework for antifreezing hydrogel development across biomedical, environmental, and soft robotic domains.

抗冻水凝胶作为低温环境下生物医学应用的有前途的材料，越来越受到人们的关注，包括低温保存、冷适应生物电子学、可穿戴传感和组织工程。尽管最近取得了进展，但这仍然是一个相对未被充分探索的研究领域，仍然存在许多基础和转化方面的挑战。然而，抗冻水凝胶在冷冻条件下保持柔韧性、导电性和生物相容性的独特能力强调了它们在未来生物医学和工程创新方面的巨大潜力。本文综述了抗冻水凝胶的设计原理、抗冻机理以及抗冻水凝胶的特殊应用。我们首先总结了基本的抗冻策略，包括低温保护剂的结合、聚合物网络工程、交联结构和超分子自愈设计。特别强调了在极端寒冷条件下具有综合菌株传感、温度响应和多功能生物传感能力的水凝胶的最新进展。然后，我们研究了面向低温保存的水凝胶，强调了它们抑制冰核、减少细胞内冰形成和保持生物功能的能力。该综述还探讨了基于水凝胶的冷适应生物电子学，包括低温可穿戴传感器、柔性电路和自供电接口。最后，我们讨论了临床翻译的关键考虑因素，如生物相容性、可降解性和长期稳定性。通过将分子设计与宏观性能联系起来，本文旨在为抗冻水凝胶在生物医学、环境和软机器人领域的发展建立一个前瞻性框架。

{"title":"Antifreezing hydrogels for biomedical applications from design strategies to emerging multifunctionality","authors":"Jiang Wu , Lijin Wang , Manhui Zheng , Jie Xu , Zixuan Gong , Boxuan Wu , Huacheng He , Jie Zheng","doi":"10.1016/j.bioactmat.2025.12.053","DOIUrl":"10.1016/j.bioactmat.2025.12.053","url":null,"abstract":"<div><div>Antifreezing hydrogels are gaining increasing attention as promising materials for biomedical applications in subzero environments, including cryopreservation, cold-adaptive bioelectronics, wearable sensing, and tissue engineering. Despite recent progress, this is still a relatively underexplored research area, with many fundamental and translational challenges remaining. However, the unique ability of antifreezing hydrogels to sustain flexibility, conductivity, and biological compatibility under freezing conditions underscores their immense potential for future biomedical and engineering innovations. This review provides a targeted overview of the design principles, antifreezing mechanisms, and application-specific adaptations of antifreezing hydrogels. We begin by summarizing fundamental antifreezing strategies, including the incorporation of cryoprotective agents, polymer network engineering, crosslinking architectures, and supramolecular self-healing designs. Particular emphasis is placed on recent advances in hydrogels with integrated strain-sensing, temperature-responsiveness, and multifunctional biosensing capabilities under extreme cold conditions. We then examine cryopreservation-oriented hydrogels, highlighting their ability to suppress ice nucleation, minimize intracellular ice formation, and preserve biological function. The review also explores hydrogel-based cold-adaptive bioelectronics, including low-temperature wearable sensors, flexible circuits, and self-powered interfaces. Finally, we discuss key considerations for clinical translation, such as biocompatibility, degradability, and long-term stability. By linking molecular design to macroscopic performance, this review aims to establish a forward-looking framework for antifreezing hydrogel development across biomedical, environmental, and soft robotic domains.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 463-491"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881686","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

Multifunctional polyoxomolybdate cluster loaded into hydrogel for augmented bone regeneration through synergistic immunomodulation and osteogenesis 多功能多氧钼酸盐簇加载到水凝胶中，通过协同免疫调节和成骨增强骨再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-08 DOI: 10.1016/j.bioactmat.2025.12.056

Mo Zhang , Fan Xu , Jingcheng Cao , Shihang Liu , Kehao Li , Ya Zhang , Yawen Chen , Siming Jia , Yuhang Shi , Kai Kang , Xiaofeng Du , Tao Zhang , Jing Wang , Wei Chen

Fracture nonunion or delayed union presents a significant challenge in orthopedic practice. Bone healing is a complex physiological process that initiates with the modulation of inflammatory immunity and progresses through critical stages, including angiogenesis, osteogenic differentiation, and biomineralization. The intrinsic link among immune homeostasis, bacterial clearance, and osteogenic microenvironments underscores the need for an integrated therapeutic strategy. To address these challenges, we developed a multifunctional molybdenum-based polyoxometalate cluster (Mo-POM) modified with gallic acid (GA). Theoretical and experimental evidence confirms that electron transfer from GA to the Mo-POM cluster narrows the HOMO-LUMO energy gap, enhancing its multi-enzyme mimetic activity for effective reactive oxygen species (ROS) scavenging, thereby remodeling the immune microenvironment. The Mo-POM also exhibits broad-spectrum antibacterial function through synergistic disruption of bacterial membranes and biofilms. To ensure practical applicability and sustained release, the Mo-POM was encapsulated within a gellan gum/nano-hydroxyapatite (GG/nHA) hydrogel scaffold. The resulting Mo-POM@GG/nHA system effectively coordinates early immunomodulation and antibacterial activity with enhanced biomineralization in the bone regeneration process. Although polyoxometalates have demonstrated versatile biochemical properties, their application in bone regeneration remains largely unexplored. This work demonstrates that a single Mo-POM cluster acts as a core modulator, achieving the “three birds with one stone” effect by eliminating inflammation, modulating the immune microenvironment, and boosting osteogenesis, thereby providing a new avenue for designing a new class of integrated biomaterials for orthopedic applications.

骨折不愈合或延迟愈合是骨科实践中的一个重大挑战。骨愈合是一个复杂的生理过程，始于炎症免疫的调节，并经历了包括血管生成、成骨分化和生物矿化在内的关键阶段。免疫稳态、细菌清除和成骨微环境之间的内在联系强调了综合治疗策略的必要性。为了解决这些挑战，我们开发了一种用没食子酸（GA）修饰的多功能钼基多金属氧酸簇（Mo-POM）。理论和实验证据证实，从GA到Mo-POM簇的电子转移缩小了HOMO-LUMO的能隙，增强了其有效清除活性氧（ROS）的多酶模拟活性，从而重塑了免疫微环境。Mo-POM还通过协同破坏细菌膜和生物膜而表现出广谱抗菌功能。为了确保实用性和缓释性，Mo-POM被封装在结冷胶/纳米羟基磷灰石（GG/nHA）水凝胶支架中。由此产生的Mo-POM@GG/nHA系统有效地协调了骨再生过程中早期免疫调节和抗菌活性与增强的生物矿化。虽然多金属氧酸盐已经证明了多种生化特性，但它们在骨再生中的应用仍未被广泛探索。这项工作表明，单个Mo-POM簇作为核心调节剂，通过消除炎症、调节免疫微环境和促进成骨实现“一石三鸟”的效果，从而为设计一类用于骨科应用的新型集成生物材料提供了新的途径。

{"title":"Multifunctional polyoxomolybdate cluster loaded into hydrogel for augmented bone regeneration through synergistic immunomodulation and osteogenesis","authors":"Mo Zhang , Fan Xu , Jingcheng Cao , Shihang Liu , Kehao Li , Ya Zhang , Yawen Chen , Siming Jia , Yuhang Shi , Kai Kang , Xiaofeng Du , Tao Zhang , Jing Wang , Wei Chen","doi":"10.1016/j.bioactmat.2025.12.056","DOIUrl":"10.1016/j.bioactmat.2025.12.056","url":null,"abstract":"<div><div>Fracture nonunion or delayed union presents a significant challenge in orthopedic practice. Bone healing is a complex physiological process that initiates with the modulation of inflammatory immunity and progresses through critical stages, including angiogenesis, osteogenic differentiation, and biomineralization. The intrinsic link among immune homeostasis, bacterial clearance, and osteogenic microenvironments underscores the need for an integrated therapeutic strategy. To address these challenges, we developed a multifunctional molybdenum-based polyoxometalate cluster (Mo-POM) modified with gallic acid (GA). Theoretical and experimental evidence confirms that electron transfer from GA to the Mo-POM cluster narrows the HOMO-LUMO energy gap, enhancing its multi-enzyme mimetic activity for effective reactive oxygen species (ROS) scavenging, thereby remodeling the immune microenvironment. The Mo-POM also exhibits broad-spectrum antibacterial function through synergistic disruption of bacterial membranes and biofilms. To ensure practical applicability and sustained release, the Mo-POM was encapsulated within a gellan gum/nano-hydroxyapatite (GG/nHA) hydrogel scaffold. The resulting Mo-POM@GG/nHA system effectively coordinates early immunomodulation and antibacterial activity with enhanced biomineralization in the bone regeneration process. Although polyoxometalates have demonstrated versatile biochemical properties, their application in bone regeneration remains largely unexplored. This work demonstrates that a single Mo-POM cluster acts as a core modulator, achieving the “three birds with one stone” effect by eliminating inflammation, modulating the immune microenvironment, and boosting osteogenesis, thereby providing a new avenue for designing a new class of integrated biomaterials for orthopedic applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 662-677"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922345","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

Fluorous oligoarginines as supra-enhancers for intracellular and transdermal peptide delivery 含氟低精氨酸作为细胞内和透皮肽传递的超级增强剂

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2025-12-30 DOI: 10.1016/j.bioactmat.2025.12.027

Guangyu Rong , Qianqian Fan , Kunyu Chen , Yiyun Cheng , Jingjing Hu

Peptides are increasingly recognized as important therapeutics due to their specificity and potency. However, their clinical application is often hindered by numerous barriers, including low bioavailability, poor cell membrane and tissue penetration. To address these limitations, we developed a library of fluorous penetrating peptides and identified fluorinated hexa-arginine (FR6) as a super-enhancer for cell and tissue penetration. FR6 markedly enhances the intracellular delivery of a variety of peptides by improving membrane permeability, facilitating their uptake across diverse cell types. It greatly improves the penetration of bioactive peptides in 3D tumor spheroids, allowing for improved therapeutic efficacy. More importantly, FR6 demonstrates remarkable potential for transdermal delivery of peptide drugs, effectively enhancing the penetration of peptides like acetyl hexapeptide-8 for treating UVB-induced skin photoaging. Our findings underscore the use of FR6 as a super-enhancer in overcoming multiple physiological barriers during cell, tissue and transdermal delivery.

多肽由于其特异性和效力越来越被认为是重要的治疗药物。然而，它们的临床应用常常受到许多障碍的阻碍，包括生物利用度低、细胞膜和组织穿透性差。为了解决这些限制，我们开发了一个含氟穿透肽库，并确定了氟化六精氨酸（FR6）作为细胞和组织穿透的超级增强剂。FR6通过改善细胞膜通透性，促进多种多肽在不同细胞类型中的摄取，从而显著增强多种多肽的细胞内递送。它大大提高了生物活性肽在三维肿瘤球体中的渗透，从而提高了治疗效果。更重要的是，FR6在多肽药物的透皮递送方面表现出了显著的潜力，可以有效地增强乙酰六肽-8等肽的渗透，从而治疗uvb诱导的皮肤光老化。我们的研究结果强调了FR6作为一种超级增强剂在克服细胞、组织和透皮递送过程中的多重生理障碍中的作用。

{"title":"Fluorous oligoarginines as supra-enhancers for intracellular and transdermal peptide delivery","authors":"Guangyu Rong , Qianqian Fan , Kunyu Chen , Yiyun Cheng , Jingjing Hu","doi":"10.1016/j.bioactmat.2025.12.027","DOIUrl":"10.1016/j.bioactmat.2025.12.027","url":null,"abstract":"<div><div>Peptides are increasingly recognized as important therapeutics due to their specificity and potency. However, their clinical application is often hindered by numerous barriers, including low bioavailability, poor cell membrane and tissue penetration. To address these limitations, we developed a library of fluorous penetrating peptides and identified fluorinated hexa-arginine (FR6) as a super-enhancer for cell and tissue penetration. FR6 markedly enhances the intracellular delivery of a variety of peptides by improving membrane permeability, facilitating their uptake across diverse cell types. It greatly improves the penetration of bioactive peptides in 3D tumor spheroids, allowing for improved therapeutic efficacy. More importantly, FR6 demonstrates remarkable potential for transdermal delivery of peptide drugs, effectively enhancing the penetration of peptides like acetyl hexapeptide-8 for treating UVB-induced skin photoaging. Our findings underscore the use of FR6 as a super-enhancer in overcoming multiple physiological barriers during cell, tissue and transdermal delivery.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 305-316"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881690","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

Prototissues: Assembly strategies, collective behaviors, and emerging applications 原组织：组装策略、集体行为和新兴应用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-10 DOI: 10.1016/j.bioactmat.2025.12.033

Ziqi Liu , Yiming Wang , Wei Pei , Yi-Xin Huo , Yuan Lu

Recent advances in bottom-up synthetic biology have significantly expanded the ability to construct artificial life systems. While most efforts focus on building protocells, many biomimetic functions arise only when multiple units operate collectively. Prototissues, formed from interconnected protocell assemblies, provide a platform for such emergent behaviors and offer broad potential in biomedicine, biosensing, and smart materials. This review introduces a dual-dimensional framework for understanding prototissue design. The first dimension examines inter-protocell adhesion strategies that define molecular connectivity, and the second examines spatial programming approaches that organize protocells into functional architectures. On this basis, the review summarizes key collective behaviors enabled by these design principles and highlights how advances in materials chemistry, synthetic biology, and advanced manufacturing support the development of increasingly adaptive and functional prototissues. Major challenges remain, including achieving dynamic and selective adhesion, scaling spatial architectures while maintaining resolution, improving signal transport, and enhancing biological integration. The review outlines potential pathways to address these issues and to guide the development of prototissues with more sophisticated, life-like properties. Overall, the conceptual framework and insights presented here provide a foundation for the rational design of next-generation prototissues and advance bottom-up synthetic biology toward more complex artificial life systems.

自底向上合成生物学的最新进展大大扩展了构建人工生命系统的能力。虽然大多数努力都集中在构建原始细胞上，但许多仿生功能只有在多个单元共同运作时才会出现。由相互连接的原始细胞集合形成的原始组织为这些紧急行为提供了平台，并在生物医学，生物传感和智能材料方面提供了广阔的潜力。本文介绍了一个理解原组织设计的二维框架。第一个维度考察了定义分子连通性的原细胞间粘附策略，第二个维度考察了将原细胞组织成功能架构的空间编程方法。在此基础上，本文总结了这些设计原则所带来的关键集体行为，并强调了材料化学、合成生物学和先进制造技术的进步如何支持越来越多的适应性和功能性原型组织的发展。主要挑战仍然存在，包括实现动态和选择性粘附，在保持分辨率的同时缩放空间结构，改善信号传输和增强生物整合。这篇综述概述了解决这些问题的潜在途径，并指导具有更复杂、类生命特性的原始组织的发展。总体而言，本文提出的概念框架和见解为下一代原始组织的合理设计提供了基础，并将自下而上的合成生物学推向更复杂的人工生命系统。

{"title":"Prototissues: Assembly strategies, collective behaviors, and emerging applications","authors":"Ziqi Liu , Yiming Wang , Wei Pei , Yi-Xin Huo , Yuan Lu","doi":"10.1016/j.bioactmat.2025.12.033","DOIUrl":"10.1016/j.bioactmat.2025.12.033","url":null,"abstract":"<div><div>Recent advances in bottom-up synthetic biology have significantly expanded the ability to construct artificial life systems. While most efforts focus on building protocells, many biomimetic functions arise only when multiple units operate collectively. Prototissues, formed from interconnected protocell assemblies, provide a platform for such emergent behaviors and offer broad potential in biomedicine, biosensing, and smart materials. This review introduces a dual-dimensional framework for understanding prototissue design. The first dimension examines inter-protocell adhesion strategies that define molecular connectivity, and the second examines spatial programming approaches that organize protocells into functional architectures. On this basis, the review summarizes key collective behaviors enabled by these design principles and highlights how advances in materials chemistry, synthetic biology, and advanced manufacturing support the development of increasingly adaptive and functional prototissues. Major challenges remain, including achieving dynamic and selective adhesion, scaling spatial architectures while maintaining resolution, improving signal transport, and enhancing biological integration. The review outlines potential pathways to address these issues and to guide the development of prototissues with more sophisticated, life-like properties. Overall, the conceptual framework and insights presented here provide a foundation for the rational design of next-generation prototissues and advance bottom-up synthetic biology toward more complex artificial life systems.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 697-723"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973731","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

Carrier free oral Co-delivery of atorvastatin via baicalein-copper-network for atherosclerosis therapy through senescence reversal and multi-mechanistic synergy 通过黄芩素-铜网络无载体口服阿托伐他汀通过衰老逆转和多机制协同治疗动脉粥样硬化

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-05 DOI: 10.1016/j.bioactmat.2025.12.036

Kaijing Liu , Gen Li , Xiaoyu Liang, Changduo Wang, Ni Zhu, Xue Fu, Yujie Zhang, Chao Liu, Jing Yang

Atherosclerosis (AS) progression is driven by multiple interconnected pathological mechanisms. Among them, vascular senescence is both a key accelerator and consequence, interacting with other processes to promote AS development. Traditional monotherapies were limited to achieve synergistic therapeutic effects due to low oral bioavailability and insufficient multi-target efficacy. To overcome these limitations, we developed a baicalein-copper network (Cu-MON) for oral delivery of atorvastatin (ATV), forming a synergistic therapeutic system (CMA). Cu-MON significantly prolonged the gastrointestinal residence and increased the oral bioavailability of ATV without requiring additional excipients. Crucially, Cu-MON regulated senescence-associated genes, enhanced DNA repair pathways, and mitigated DNA damage, effectively counteracting vascular aging. The integrated CMA system combined enzymatic and non-enzymatic dual antioxidant systems to scavenge multiple ROS species. Furthermore, CMA reprogrammed macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, modulated the PPAR-γ/LXR-α/ABCA-1 pathway to enhance cholesterol efflux, inhibited foam cell formation, and regulated hepatic and systemic cholesterol homeostasis. In ApoE^−/− mice, CMA markedly reduced aortic plaque burden and fibrosis, while Cu-MON attenuated key features of AS, including decreased ROS, inflammation, DNA damage, and cellular senescence. The CMA demonstrates high synergistic efficacy and biosafety, offering a novel multi-target oral drug strategy for AS treatment.

动脉粥样硬化（AS）的进展是由多种相互关联的病理机制驱动的。其中，血管衰老既是关键的加速器，也是关键的后果，与其他过程相互作用，促进AS的发展。由于口服生物利用度低，多靶点疗效不足，传统单药治疗难以达到协同治疗效果。为了克服这些局限性，我们开发了黄芩素-铜网络（Cu-MON）用于口服阿托伐他汀（ATV），形成一个协同治疗系统（CMA）。Cu-MON显著延长了ATV的胃肠道停留时间，增加了ATV的口服生物利用度，而无需额外的辅料。重要的是，Cu-MON调节衰老相关基因，增强DNA修复途径，减轻DNA损伤，有效地对抗血管老化。综合CMA系统结合酶和非酶双抗氧化系统清除多种活性氧。此外，CMA将巨噬细胞从促炎M1型重编程为抗炎M2型，调节PPAR-γ/LXR-α/ABCA-1通路，增强胆固醇外排，抑制泡沫细胞形成，调节肝脏和全身胆固醇稳态。在ApoE−/−小鼠中，CMA显著减轻了主动脉斑块负担和纤维化，而Cu-MON则减轻了AS的关键特征，包括ROS减少、炎症、DNA损伤和细胞衰老。CMA具有较高的协同效应和生物安全性，为治疗AS提供了一种新的多靶点口服药物策略。

{"title":"Carrier free oral Co-delivery of atorvastatin via baicalein-copper-network for atherosclerosis therapy through senescence reversal and multi-mechanistic synergy","authors":"Kaijing Liu , Gen Li , Xiaoyu Liang, Changduo Wang, Ni Zhu, Xue Fu, Yujie Zhang, Chao Liu, Jing Yang","doi":"10.1016/j.bioactmat.2025.12.036","DOIUrl":"10.1016/j.bioactmat.2025.12.036","url":null,"abstract":"<div><div>Atherosclerosis (AS) progression is driven by multiple interconnected pathological mechanisms. Among them, vascular senescence is both a key accelerator and consequence, interacting with other processes to promote AS development. Traditional monotherapies were limited to achieve synergistic therapeutic effects due to low oral bioavailability and insufficient multi-target efficacy. To overcome these limitations, we developed a baicalein-copper network (Cu-MON) for oral delivery of atorvastatin (ATV), forming a synergistic therapeutic system (CMA). Cu-MON significantly prolonged the gastrointestinal residence and increased the oral bioavailability of ATV without requiring additional excipients. Crucially, Cu-MON regulated senescence-associated genes, enhanced DNA repair pathways, and mitigated DNA damage, effectively counteracting vascular aging. The integrated CMA system combined enzymatic and non-enzymatic dual antioxidant systems to scavenge multiple ROS species. Furthermore, CMA reprogrammed macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, modulated the PPAR-γ/LXR-α/ABCA-1 pathway to enhance cholesterol efflux, inhibited foam cell formation, and regulated hepatic and systemic cholesterol homeostasis. In ApoE<sup>−/−</sup> mice, CMA markedly reduced aortic plaque burden and fibrosis, while Cu-MON attenuated key features of AS, including decreased ROS, inflammation, DNA damage, and cellular senescence. The CMA demonstrates high synergistic efficacy and biosafety, offering a novel multi-target oral drug strategy for AS treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 555-578"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922243","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

Multimodal profiling of CAR T cells against glioblastoma using a microengineered 3D tumor-on-a-chip model 使用微工程3D肿瘤芯片模型的CAR - T细胞对抗胶质母细胞瘤的多模态分析

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-10 DOI: 10.1016/j.bioactmat.2026.01.003

Kalpana Ravi , Shannon Trottier , Obed B. Amissah , Grace C. Russell , Daniel Rho , Gloria B. Kim , Mehdi Nikkhah

Immunotherapies such as chimeric antigen receptor (CAR) T cells have shown promising outcomes in hematological cancer but face challenges in targeting solid tumors like glioblastoma (GBM). Advancing this therapy for GBM has been hindered by the lack of preclinical tools that accurately model the complex interplay between CAR T cells and tumor cells within the tumor microenvironment (TME) — interactions critical for optimizing CAR constructs and improving efficacy. Physiologically relevant models that closely mimic the solid TME are therefore highly sought after in developing CAR T therapies. Here, we report a microengineered glioblastoma-on-a-chip (GOC) model with a functional vascular network to investigate the efficacy and selectivity of IL-13 mutein CAR T cells (TV-13) against U87 GBM tumor cells expressing high interleukin-13 receptor alpha-2 (IL13Rα2), compared with the ubiquitously expressed IL13Rα1. This biomimetic platform recapitulates the GBM TME and enables dynamic evaluation of CAR T cell responses under locoregional administration, paralleling clinical approaches. Using the organotypic GOC model, we evaluated CAR T cell-mediated inhibition of GBM invasion, monitored real-time dynamic CAR T-U87 interactions, and quantified the release of cytotoxic, proinflammatory, and stimulation-associated cytokines as measures of T cell effector function. CAR T cells induced a density-dependent reduction in U87 migration, accompanied by robust cytokine release, while TV-13 maintained specificity towards IL13Rα2 tumor antigen over IL13Rα1. Additionally, we further demonstrated the efficacy of CAR T cells against patient-derived GBM cells within the GOC model. Collectively, these findings highlight the GOC platform as a powerful preclinical screening tool for cancer immunotherapy optimization.

嵌合抗原受体（CAR） T细胞等免疫疗法在血液病治疗中显示出良好的效果，但在靶向胶质母细胞瘤（GBM）等实体肿瘤方面面临挑战。由于缺乏临床前工具来准确模拟肿瘤微环境（TME）中CAR - T细胞和肿瘤细胞之间复杂的相互作用，这种相互作用对于优化CAR结构和提高疗效至关重要，因此阻碍了这种治疗GBM的进展。因此，在开发CAR - T疗法时，密切模仿实体TME的生理学相关模型受到高度追捧。在这里，我们报道了一个具有功能血管网络的微工程胶质母细胞瘤芯片（GOC）模型，以研究IL-13突变蛋白CAR - T细胞（电视-13）对表达高白介素-13受体α -2 （IL13Rα2）的U87 GBM肿瘤细胞的疗效和选择性，并与普遍表达的IL13Rα1进行比较。这个仿生平台概括了GBM TME，并能够在局部管理下动态评估CAR - T细胞反应，与临床方法平行。使用器官型GOC模型，我们评估了CAR - T细胞介导的GBM侵袭抑制，监测了实时动态CAR - T- u87相互作用，并量化了细胞毒性、促炎和刺激相关细胞因子的释放，作为T细胞效应功能的测量。CAR - T细胞诱导了U87迁移的密度依赖性减少，并伴有强劲的细胞因子释放，而TV-13对IL13Rα2肿瘤抗原的特异性高于IL13Rα1。此外，我们在GOC模型中进一步证明了CAR - T细胞对患者来源的GBM细胞的有效性。总的来说，这些发现突出了GOC平台作为癌症免疫治疗优化的强大临床前筛查工具。

{"title":"Multimodal profiling of CAR T cells against glioblastoma using a microengineered 3D tumor-on-a-chip model","authors":"Kalpana Ravi , Shannon Trottier , Obed B. Amissah , Grace C. Russell , Daniel Rho , Gloria B. Kim , Mehdi Nikkhah","doi":"10.1016/j.bioactmat.2026.01.003","DOIUrl":"10.1016/j.bioactmat.2026.01.003","url":null,"abstract":"<div><div>Immunotherapies such as chimeric antigen receptor (CAR) T cells have shown promising outcomes in hematological cancer but face challenges in targeting solid tumors like glioblastoma (GBM). Advancing this therapy for GBM has been hindered by the lack of preclinical tools that accurately model the complex interplay between CAR T cells and tumor cells within the tumor microenvironment (TME) — interactions critical for optimizing CAR constructs and improving efficacy. Physiologically relevant models that closely mimic the solid TME are therefore highly sought after in developing CAR T therapies. Here, we report a microengineered glioblastoma-on-a-chip (GOC) model with a functional vascular network to investigate the efficacy and selectivity of IL-13 mutein CAR T cells (TV-13) against U87 GBM tumor cells expressing high interleukin-13 receptor alpha-2 (IL13Rα2), compared with the ubiquitously expressed IL13Rα1. This biomimetic platform recapitulates the GBM TME and enables dynamic evaluation of CAR T cell responses under locoregional administration, paralleling clinical approaches. Using the organotypic GOC model, we evaluated CAR T cell-mediated inhibition of GBM invasion, monitored real-time dynamic CAR T-U87 interactions, and quantified the release of cytotoxic, proinflammatory, and stimulation-associated cytokines as measures of T cell effector function. CAR T cells induced a density-dependent reduction in U87 migration, accompanied by robust cytokine release, while TV-13 maintained specificity towards IL13Rα2 tumor antigen over IL13Rα1. Additionally, we further demonstrated the efficacy of CAR T cells against patient-derived GBM cells within the GOC model. Collectively, these findings highlight the GOC platform as a powerful preclinical screening tool for cancer immunotherapy optimization.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 724-744"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973730","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

Assembly of bioinspired multifunctional microspheres for enhanced alveolar bone regeneration 生物激发多功能微球的组装促进牙槽骨再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2026-01-31 DOI: 10.1016/j.bioactmat.2026.01.032

Yingzi Li , Qian Li , Zhaoming Deng , Xiaohua Liu

Regeneration of the alveolar bone remains a major clinical challenge due to the complex oral microenvironment and the need for coordinated restoration of multiple tissue types. To overcome these hurdles, biomaterials designed for periodontal regeneration must meet a rigorous set of criteria, including excellent injectability, mechanical stability, selective cell repopulation, and strong osteoinductive capacity. In this study, we developed a bioinspired, multifunctional microsphere system that fulfills these requirements. The system is injectable, mechanically robust, selectively binds bone marrow-derived stem cells (BMSCs), and exhibits potent osteoinductivity. These multifunctional properties were achieved by UV-assembling nanofibrous hollow microspheres (NFH-MS), conjugating the BMSC-specific E7 peptide to the nanofibrous shell, and encapsulating a bone-forming peptide (BFP) within the hollow core. UV-assembly enhanced the scaffold's mechanical integrity, generated interconnected macropores to support cell infiltration, and promoted intercellular communication. Notably, it significantly upregulated Connexin 43 and N-cadherin-mediated junctions, further facilitating cellular interactions. In synergy with E7 and BFP, the UV-assembled NFH-MS scaffold markedly improved BMSC adhesion, osteogenic differentiation, and biomineralization. This bioinspired multifunctional NFH-MS platform demonstrated superior alveolar bone regeneration in a rat fenestration defect model, offering a promising and minimally invasive strategy for periodontal tissue engineering.

由于复杂的口腔微环境和多种组织类型需要协调修复，牙槽骨的再生仍然是一个重大的临床挑战。为了克服这些障碍，设计用于牙周再生的生物材料必须满足一系列严格的标准，包括良好的可注射性、机械稳定性、选择性细胞再生和强大的骨诱导能力。在这项研究中，我们开发了一种生物启发的多功能微球系统来满足这些要求。该系统是可注射的，机械坚固，选择性结合骨髓源性干细胞（BMSCs），并表现出强大的骨诱导能力。这些多功能特性是通过紫外线组装纳米纤维空心微球（NFH-MS），将bmsc特异性E7肽偶联到纳米纤维外壳上，并在空心核心内封装成骨肽（BFP）来实现的。uv组装增强了支架的机械完整性，产生相互连接的大孔以支持细胞浸润，促进细胞间的通讯。值得注意的是，它显著上调了Connexin 43和n- cadherin介导的连接，进一步促进了细胞相互作用。在与E7和BFP的协同作用下，uv组装的NFH-MS支架显著改善了BMSC的粘附、成骨分化和生物矿化。这种生物启发的多功能NFH-MS平台在大鼠开窗缺损模型中表现出优越的牙槽骨再生能力，为牙周组织工程提供了一种有前途的微创策略。

{"title":"Assembly of bioinspired multifunctional microspheres for enhanced alveolar bone regeneration","authors":"Yingzi Li , Qian Li , Zhaoming Deng , Xiaohua Liu","doi":"10.1016/j.bioactmat.2026.01.032","DOIUrl":"10.1016/j.bioactmat.2026.01.032","url":null,"abstract":"<div><div>Regeneration of the alveolar bone remains a major clinical challenge due to the complex oral microenvironment and the need for coordinated restoration of multiple tissue types. To overcome these hurdles, biomaterials designed for periodontal regeneration must meet a rigorous set of criteria, including excellent injectability, mechanical stability, selective cell repopulation, and strong osteoinductive capacity. In this study, we developed a bioinspired, multifunctional microsphere system that fulfills these requirements. The system is injectable, mechanically robust, selectively binds bone marrow-derived stem cells (BMSCs), and exhibits potent osteoinductivity. These multifunctional properties were achieved by UV-assembling nanofibrous hollow microspheres (NFH-MS), conjugating the BMSC-specific E7 peptide to the nanofibrous shell, and encapsulating a bone-forming peptide (BFP) within the hollow core. UV-assembly enhanced the scaffold's mechanical integrity, generated interconnected macropores to support cell infiltration, and promoted intercellular communication. Notably, it significantly upregulated Connexin 43 and N-cadherin-mediated junctions, further facilitating cellular interactions. In synergy with E7 and BFP, the UV-assembled NFH-MS scaffold markedly improved BMSC adhesion, osteogenic differentiation, and biomineralization. This bioinspired multifunctional NFH-MS platform demonstrated superior alveolar bone regeneration in a rat fenestration defect model, offering a promising and minimally invasive strategy for periodontal tissue engineering.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 781-795"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074041","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

Microenvironment-mediated stem cell fate in periodontal tissue remodeling and repair 微环境介导的干细胞命运在牙周组织重塑和修复中的作用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.025

Jin-Xuan Zheng , Han Yin , Guang-Zhao Tian , Zi-Feng Quan , Zhi-Li Dong , Wen-Qian Ding , Zeng-Xuan Wang , Yu-Ting Niu , Quan-Yi Guo , Yi-Qi Tang , Wei-Min Guo

The cellular microenvironment is an integrated complex of the extracellular matrix, cells and extracellular fluids containing numerous bioactive molecules. It is widely acknowledged that the periodontal microenvironment exerts profound effects on adjacent stem cells, affecting tissue remodeling and repair. For instance, the physiological microenvironment maintains stemness and supports tissue-specific differentiation of mesenchymal stem cells (MSCs), whereas pathological inflammation resets programmed cell fate, increases the secretion of proinflammatory factors, and may even induce MSC apoptosis. The normal remodeling or repair process is therefore dysregulated, and inflammatory conditions worsen. Modulating the stem cell-based microenvironment appears to be an effective strategy for periodontal regeneration. In this review, five types of MSCs involved in periodontal tissue remodeling and repair are introduced. Subsequently, we discuss the impact of various periodontal microenvironments on MSC fate and further summarize the latest biomaterials for use in periodontal regeneration from the aspect of microenvironmental cues. The use of multiple material design strategies to modify the inflammatory microenvironment offers valuable insights for future advancement of material-guided periodontal regeneration under pathological conditions.

细胞微环境是细胞外基质、细胞和含有大量生物活性分子的细胞外液的综合复合体。人们普遍认为牙周微环境对邻近干细胞具有深远的影响，影响组织的重塑和修复。例如，生理微环境维持干细胞的干性并支持间充质干细胞（MSCs）的组织特异性分化，而病理性炎症重置程序性细胞命运，增加促炎因子的分泌，甚至可能诱导间充质干细胞凋亡。正常的重塑或修复过程因此失调，炎症状况恶化。调节干细胞微环境似乎是牙周再生的有效策略。本文就参与牙周组织重塑和修复的5种间充质干细胞进行综述。随后，我们讨论了各种牙周微环境对MSC命运的影响，并从微环境线索方面进一步总结了最新的用于牙周再生的生物材料。使用多种材料设计策略来改变炎症微环境，为病理条件下材料引导牙周再生的未来发展提供了有价值的见解。

{"title":"Microenvironment-mediated stem cell fate in periodontal tissue remodeling and repair","authors":"Jin-Xuan Zheng , Han Yin , Guang-Zhao Tian , Zi-Feng Quan , Zhi-Li Dong , Wen-Qian Ding , Zeng-Xuan Wang , Yu-Ting Niu , Quan-Yi Guo , Yi-Qi Tang , Wei-Min Guo","doi":"10.1016/j.bioactmat.2025.12.025","DOIUrl":"10.1016/j.bioactmat.2025.12.025","url":null,"abstract":"<div><div>The cellular microenvironment is an integrated complex of the extracellular matrix, cells and extracellular fluids containing numerous bioactive molecules. It is widely acknowledged that the periodontal microenvironment exerts profound effects on adjacent stem cells, affecting tissue remodeling and repair. For instance, the physiological microenvironment maintains stemness and supports tissue-specific differentiation of mesenchymal stem cells (MSCs), whereas pathological inflammation resets programmed cell fate, increases the secretion of proinflammatory factors, and may even induce MSC apoptosis. The normal remodeling or repair process is therefore dysregulated, and inflammatory conditions worsen. Modulating the stem cell-based microenvironment appears to be an effective strategy for periodontal regeneration. In this review, five types of MSCs involved in periodontal tissue remodeling and repair are introduced. Subsequently, we discuss the impact of various periodontal microenvironments on MSC fate and further summarize the latest biomaterials for use in periodontal regeneration from the aspect of microenvironmental cues. The use of multiple material design strategies to modify the inflammatory microenvironment offers valuable insights for future advancement of material-guided periodontal regeneration under pathological conditions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 69-95"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838818","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 promising magnesium-related alloy with metabolic reprogramming and antitumor effects in hepatocellular and pancreatic cancer 一种在肝细胞癌和胰腺癌中具有代谢重编程和抗肿瘤作用的镁相关合金

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-05-01 Epub Date: 2025-12-27 DOI: 10.1016/j.bioactmat.2025.12.039

Junfeng Zhang , Jianyou Gu , Renpei Xia , Jingyang Yin , Xianxing Wang , Jiali Yang , Yanjun Wang , Zhongchao Yi , Senwei Wang , Qifan Zhang , Huaizhi Wang , Jia She , Shixiang Guo

Hepatocellular and pancreatic cancers are highly aggressive malignancies with dismal clinical outcomes, highlighting an urgent need for new therapeutic strategies. Magnesium-related alloys, widely explored for their biocompatibility and bioactivity, are attractive candidates for biliary and pancreatic duct stents. However, their antitumor potential and underlying mechanisms remain incompletely defined. Here, we systematically characterized the physicochemical properties and anticancer activities of a panel of magnesium-related alloy powders and identified an aluminum-magnesium (Al-Mg) alloy as the most potent candidate. Compared with pure Mg, Al-Mg rods exhibited stronger antitumor efficacy together with more controllable degradation. In vitro and in vivo assays confirmed that Al-Mg significantly inhibited hepatocellular carcinoma and pancreatic cancer progression. Integrated metabolomic and transcriptomic analyses indicated that Al-Mg activates AMPK signaling and suppresses purine and pyrimidine metabolism, consistent with metabolic reprogramming that limits tumor cell proliferation. Furthermore, single-cell and spatial transcriptomic analyses delineated Al-Mg-sensitive tumor cell subpopulations and mapped their spatial distribution within pancreatic cancer tissues. Collectively, these findings position Al-Mg as a promising antitumor material and provide a mechanistic framework supporting the development of magnesium-related alloys for local oncologic intervention.

肝细胞癌和胰腺癌是高度侵袭性的恶性肿瘤，临床结果令人沮丧，迫切需要新的治疗策略。镁合金因其生物相容性和生物活性而被广泛研究，是胆管和胰管支架有吸引力的候选者。然而，它们的抗肿瘤潜能和潜在机制仍未完全确定。在这里，我们系统地表征了一组镁相关合金粉末的物理化学性质和抗癌活性，并确定了一种铝镁（Al-Mg）合金是最有效的候选者。与纯Mg相比，Al-Mg棒具有更强的抗肿瘤作用，且降解更可控。体外和体内实验证实，Al-Mg显著抑制肝细胞癌和胰腺癌的进展。综合代谢组学和转录组学分析表明，Al-Mg激活AMPK信号并抑制嘌呤和嘧啶代谢，与限制肿瘤细胞增殖的代谢重编程一致。此外，单细胞和空间转录组学分析描绘了al - mg敏感的肿瘤细胞亚群，并绘制了它们在胰腺癌组织中的空间分布。总的来说，这些发现表明Al-Mg是一种很有前途的抗肿瘤材料，并为局部肿瘤干预中镁相关合金的开发提供了机制框架。

{"title":"A promising magnesium-related alloy with metabolic reprogramming and antitumor effects in hepatocellular and pancreatic cancer","authors":"Junfeng Zhang , Jianyou Gu , Renpei Xia , Jingyang Yin , Xianxing Wang , Jiali Yang , Yanjun Wang , Zhongchao Yi , Senwei Wang , Qifan Zhang , Huaizhi Wang , Jia She , Shixiang Guo","doi":"10.1016/j.bioactmat.2025.12.039","DOIUrl":"10.1016/j.bioactmat.2025.12.039","url":null,"abstract":"<div><div>Hepatocellular and pancreatic cancers are highly aggressive malignancies with dismal clinical outcomes, highlighting an urgent need for new therapeutic strategies. Magnesium-related alloys, widely explored for their biocompatibility and bioactivity, are attractive candidates for biliary and pancreatic duct stents. However, their antitumor potential and underlying mechanisms remain incompletely defined. Here, we systematically characterized the physicochemical properties and anticancer activities of a panel of magnesium-related alloy powders and identified an aluminum-magnesium (Al-Mg) alloy as the most potent candidate. Compared with pure Mg, Al-Mg rods exhibited stronger antitumor efficacy together with more controllable degradation. <em>In vitro</em> and <em>in vivo</em> assays confirmed that Al-Mg significantly inhibited hepatocellular carcinoma and pancreatic cancer progression. Integrated metabolomic and transcriptomic analyses indicated that Al-Mg activates AMPK signaling and suppresses purine and pyrimidine metabolism, consistent with metabolic reprogramming that limits tumor cell proliferation. Furthermore, single-cell and spatial transcriptomic analyses delineated Al-Mg-sensitive tumor cell subpopulations and mapped their spatial distribution within pancreatic cancer tissues. Collectively, these findings position Al-Mg as a promising antitumor material and provide a mechanistic framework supporting the development of magnesium-related alloys for local oncologic intervention.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 186-204"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838819","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