Bioactive Materials最新文献_第8页

Cell-only bioprinting of articular cartilage progenitor cells within a physically constraining support bath to engineer structurally organized grafts 关节软骨祖细胞在物理限制的支持浴中进行细胞生物打印，以设计结构组织的移植物

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-29 DOI: 10.1016/j.bioactmat.2025.12.013

Aliaa S. Karam , Gabriela S. Kronemberger , Kaoutar Chattahy , Daniel J. Kelly

Engineering functional articular cartilage (AC) grafts is one of the greatest challenges in tissue engineering. Recapitulating the arcade-like collagen organisation of AC, which is integral to the tissues’ strength and stiffness, is necessary to engineer truly functional grafts. This motivates the need for innovative strategies to control collagen alignment in engineered tissues in a programmable manner. Emerging 3D bioprinting strategies can provide spatially defined cues to guide tissue growth. Therefore, the goal of this study was to use embedded bioprinting to provide spatially defined boundary conditions to AC progenitor cells (ACP) to direct collagen organization and support the development of biomimetic cartilage tissues. ACPs were isolated through differential adhesion to fibronectin and demonstrated superior chondrogenesis to donor matched chondrocytes. Two different approaches (casting and 3D bioprinting) were used to physically constrain ACPs with external boundaries of differing widths (250, 500, or 750 μm). For both approaches, thinner boundaries promoted greater collagen alignment along the long axis of the developing tissue. Building on this, ACPs were bioprinted into a sheet, with collagen fibers aligning parallel to the print direction. Finally, a multi-layered graft was bioprinted with horizontal filaments (XY plane) overlaying vertical filaments (Z-axis). The bioprinted tissue had an arcade-like collagen organization with horizontal collagen fibres overlaying vertical collagen fibres. These findings demonstrate how support baths can be used to provide spatially defined physical boundary conditions to bioprinted cells to guide matrix organization, enabling the engineering of anisotropic AC grafts.

工程功能关节软骨（AC）移植是组织工程中最大的挑战之一。概括AC的拱廊状胶原组织，这是组织强度和刚度的组成部分，是设计真正功能移植的必要条件。这激发了对创新策略的需求，以可编程的方式控制工程组织中的胶原排列。新兴的3D生物打印策略可以提供空间定义的线索来指导组织生长。因此，本研究的目的是利用嵌入式生物打印技术为AC祖细胞（ACP）提供空间定义的边界条件，以指导胶原组织并支持仿生软骨组织的发展。acp通过与纤维连接蛋白的不同粘附分离，并表现出比供体匹配的软骨细胞更优越的软骨形成。采用两种不同的方法（铸造和3D生物打印），以不同宽度（250、500或750 μm）的外部边界对acp进行物理约束。对于这两种方法，更薄的边界促进胶原蛋白沿着发育组织的长轴排列。在此基础上，acp被生物打印成薄片，胶原纤维与打印方向平行。最后，用水平丝（XY平面）覆盖垂直丝（z轴）的多层移植物进行生物打印。生物打印组织具有水平胶原纤维覆盖垂直胶原纤维的拱廊状胶原组织。这些发现表明，支撑液可以为生物打印细胞提供空间定义的物理边界条件，以指导基质组织，从而实现各向异性交流移植物的工程。

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引用次数: 0

Highly bio-adapted hydrogels for tendon-bone interface regeneration: Natural healing inspiration, design strategies, and biomedical potential 用于肌腱-骨界面再生的高度生物适应性水凝胶：自然愈合灵感、设计策略和生物医学潜力

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-29 DOI: 10.1016/j.bioactmat.2025.12.043

Xinghao Yin , Juehong Li , Cunyi Fan

Against the dual backdrop of a global push to promote physical activity and the progressive degeneration of the musculoskeletal system due to aging, a significant imbalance has emerged between life expectancy and quality of life. Tendon–bone interface (TBI) injuries markedly impair physical function and overall well-being. The anatomical gradient structure of the TBI, along with the spatiotemporal complexity of its cellular composition and distribution, poses substantial challenges to postoperative healing. This review examines the vulnerability of the TBI under physiological conditions, the spatial gradient distribution of various functional cell types, and the concentration gradients of cytokines. We further introduce the reparative processes that occur following TBI injury and highlight key strategies for interface regeneration. In recent years, advances in tissue engineering have endowed hydrogels with unique biological properties and potential to mimic the gradient architecture of native TBI tissue, making them promising candidates for TBI repair and thereby improving clinical outcomes. We categorize current hydrogel-based strategies for enhancing TBI healing into four main types: improving hydrogel physicochemical properties, mimicking native anatomical structures, replicating dynamic gradients of cells and cytokines, and responding adaptively to the healing microenvironment. Lastly, we discuss the selection of functional cells and the mechanisms through which bioactive factors contribute to TBI regeneration. In summary, this review provides insights into the design of highly bio-adapted hydrogels tailored to the gradient structure and biological property of the TBI and offers guidance for future research on hydrogel-based therapeutic strategies.

在全球推动身体活动和衰老导致肌肉骨骼系统进行性退化的双重背景下，预期寿命和生活质量之间出现了严重的不平衡。肌腱-骨界面（TBI）损伤明显损害身体功能和整体健康。TBI的解剖梯度结构，以及其细胞组成和分布的时空复杂性，对术后愈合提出了重大挑战。本文综述了脑损伤在生理条件下的易损性、各种功能细胞类型的空间梯度分布以及细胞因子的浓度梯度。我们进一步介绍了脑损伤后的修复过程，并强调了界面再生的关键策略。近年来，组织工程的进展赋予了水凝胶独特的生物学特性和模仿天然TBI组织梯度结构的潜力，使其成为TBI修复的有希望的候选者，从而改善临床结果。我们将目前用于增强创伤性脑损伤愈合的基于水凝胶的策略分为四种主要类型：改善水凝胶的物理化学性质，模仿天然解剖结构，复制细胞和细胞因子的动态梯度，以及对愈合微环境的适应性响应。最后，我们讨论了功能细胞的选择和生物活性因子促进TBI再生的机制。综上所述，本综述为设计适合TBI梯度结构和生物学特性的高度生物适应性水凝胶提供了见解，并为未来基于水凝胶的治疗策略研究提供了指导。

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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 : 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。

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引用次数: 0

Tailoring nanotopography and antibacterial properties of calcium phosphate bone grafts via fluoride incorporation 通过氟化物掺入调整磷酸钙骨移植物的纳米形貌和抗菌性能

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-27 DOI: 10.1016/j.bioactmat.2025.12.026

Carla Arca-Garcia , Maria Godoy-Gallardo , Maria-Pau Ginebra

Despite advances in bone graft design and surgical techniques, bacterial infection remains a major cause of graft failure, exacerbated by the global rise in antimicrobial resistance. This has intensified the pursuit of antibiotic-free strategies to prevent bacterial colonization. Among these, antibacterial surface nanotopographies have emerged as promising tools, leveraging nanoscale geometries to physically disrupt bacteria upon contact. In this study, we engineered the surface of a calcium phosphate bone graft to confer antimicrobial functionality through a dual approach: the creation of high-aspect-ratio nanotopographies and ionic doping with fluoride. Through controlled hydrolysis of α-tricalcium phosphate by biomimetic and hydrothermal treatments, we generated calcium deficient hydroxyapatite nanoneedle structures whose morphology and biofunctionality were tuned via fluoride incorporation. XRD and Raman spectroscopy confirmed the formation of hydroxy-fluorapatite, with phase composition and surface morphology dependent on fluoride concentration and processing parameters. Fluoride doping significantly altered nanoneedle dimensions and spacing and enhanced bactericidal activity, particularly against P. aeruginosa, and to a lesser extent S. aureus. Notably, fluoride-doping alone showed no antibacterial effects; however, when combined with nanotopography, a synergistic increase in efficacy was observed. Importantly, the antimicrobial surfaces supported the proliferation and osteogenic differentiation of SaOS-2 cells. Co-culture assays modeling pre- and post-implantation infection scenarios demonstrated robust cell adhesion and markedly reduced bacterial colonization. In conclusion, our findings present a multifunctional, synthetic bone graft with both physical and chemical antibacterial properties, offering a promising strategy to mitigate infection risks while supporting osteointegration.

尽管骨移植设计和手术技术取得了进步，但细菌感染仍然是导致骨移植失败的主要原因，全球抗菌素耐药性的上升加剧了这种情况。这加强了对无抗生素策略的追求，以防止细菌定植。其中，抗菌表面纳米形貌已成为有前途的工具，利用纳米级几何形状在接触时物理破坏细菌。在这项研究中，我们设计了磷酸钙骨移植物的表面，通过双重方法赋予抗菌功能：创建高纵横比纳米形貌和氟离子掺杂。通过仿生和水热处理对α-磷酸三钙的水解，我们得到了缺乏钙的羟基磷灰石纳米针结构，其形态和生物功能通过氟化物的掺入进行了调整。XRD和拉曼光谱证实了羟基氟磷灰石的形成，其相组成和表面形貌取决于氟化物浓度和加工参数。氟掺杂显著改变了纳米针的尺寸和间距，增强了杀菌活性，特别是对铜绿假单胞菌，在较小程度上对金黄色葡萄球菌。值得注意的是，单独掺杂氟化物没有抗菌效果；然而，当与纳米形貌相结合时，观察到药效的协同增加。重要的是，抗菌表面支持SaOS-2细胞的增殖和成骨分化。模拟植入前和植入后感染情景的共培养实验表明，细胞粘附能力强，细菌定植明显减少。总之，我们的研究结果提出了一种具有物理和化学抗菌特性的多功能合成骨移植物，为减轻感染风险同时支持骨整合提供了一种有希望的策略。

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引用次数: 0

An embolism-free nonfouling hydrogel coating with high toughness and lubricity for intravascular medical devices via chain-entanglement mediated topological gelation 一种通过链缠结介导的拓扑凝胶，用于血管内医疗器械的无栓塞、无污垢、高韧性和润滑性的水凝胶涂层

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-26 DOI: 10.1016/j.bioactmat.2025.11.033

Wenzhong Cao , Xianchi Zhou , Wenbin Dai , Zihao Zhu , Zuolong Liu , Kexin Chen , Yu Yan , Hengshuai Bao , Jian Ji , Peng Zhang

Hydrogel coatings have become indispensable for advanced interventional devices owing to their exceptional lubricity, antithrombogenicity, and antibacterial performance. However, clinical adoption has been hindered by the risk of polymer embolism resulting from coating delamination in vascular systems. Herein, we report an embolism-free hydrogel coating strategy based on chain-entanglement-mediated topological gelation to address this limitation. Through an interface-regulated polymerization process, we fabricate a robust zwitterionic hydrogel coating stabilized by interfacial interlinking and enhanced polymer chain entanglement. This design delivers outstanding long-term antimicrobial and antithrombogenic properties and achieves high toughness, ultra-low friction, and wear resistance. Notably, the chain-entangled topological hydrogel exhibits a unique fail-safe mechanism: upon detachment, it undergoes spontaneous aqueous dissolution rather than forming hazardous debris. This approach can potentially reduce life-threatening complications in interventional therapies by eliminating the risk of polymer-induced embolism.

由于其优异的润滑性、抗血栓性和抗菌性能，水凝胶涂层已成为先进介入设备不可或缺的材料。然而，由于血管系统涂层分层导致聚合物栓塞的风险，临床应用一直受到阻碍。在此，我们报告了一种基于链缠结介导的拓扑凝胶的无栓塞水凝胶涂层策略来解决这一限制。通过界面调节聚合工艺，我们制备了一种坚固的两性离子水凝胶涂层，该涂层通过界面互连和增强聚合物链纠缠来稳定。这种设计提供了出色的长期抗菌和抗血栓形成性能，并实现了高韧性，超低摩擦和耐磨性。值得注意的是，链缠绕的拓扑水凝胶表现出一种独特的故障安全机制：在脱离时，它经历了自发的水溶解，而不是形成危险的碎片。这种方法可以通过消除聚合物诱发栓塞的风险，潜在地减少介入治疗中危及生命的并发症。

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引用次数: 0

Enzyme-regulated biomineralization: Biological functions and advanced biomaterials for tissue regeneration 酶调节生物矿化：组织再生的生物功能和先进生物材料

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-25 DOI: 10.1016/j.bioactmat.2025.12.041

Qing Zhao, Mingli He, Jing Shu, Yao Huang, Jin Chen, Weihua Guo

Enzyme-regulated biomineralization offers precise spatiotemporal control over tissue mineralization, overcoming key limitations of conventional regenerative therapies. This review systematically examines the underlying biological mechanisms, focusing on enzymatic regulation of phosphate metabolism, mineralization regulators, and matrix stabilization that orchestrate hierarchical mineral deposition. Organic matrices facilitate nanoconfinement-driven nucleation and spatially controlled mineralization through biochemical functionalization. These fundamental mechanisms have inspired the development of advanced enzyme-functionalized biomaterials, such as covalently immobilized hydrogels, physically entrapped nanocomposites, bioaffinity scaffolds, and stimuli-responsive 3D-printed constructs, which enable precisely tunable in situ mineralization. In clinical applications, such biomaterial systems demonstrate significant therapeutic potential, with critical-sized bone defects showing accelerated healing through biomimetic mineral-collagen alignment and enzyme-mediated enamel restoration achieving both hardness recovery and reduced secondary caries incidence. Current limitations primarily involve enzymatic stability, immunogenicity, and manufacturing scalability. Emerging solutions focus on gene-enzyme hybrid platforms and intelligent responsive systems for personalized regenerative approaches. The synergistic integration of biological principles with materials science provides a transformative foundation for developing next-generation therapeutic strategies.

酶调节的生物矿化提供了对组织矿化的精确时空控制，克服了传统再生疗法的关键限制。这篇综述系统地研究了潜在的生物学机制，重点是磷酸盐代谢的酶调节，矿化调节和基质稳定，协调分层矿物沉积。有机基质通过生化功能化促进纳米约束驱动的成核和空间控制的矿化。这些基本机制激发了先进的酶功能化生物材料的发展，如共价固定的水凝胶、物理包裹的纳米复合材料、生物亲和性支架和刺激响应的3d打印结构，它们能够精确地调节原位矿化。在临床应用中，这种生物材料系统显示出巨大的治疗潜力，通过仿生矿物质-胶原蛋白排列和酶介导的牙釉质修复，临界尺寸的骨缺损显示出加速愈合，既能恢复硬度，又能减少继发性龋齿的发生率。目前的限制主要涉及酶的稳定性、免疫原性和制造的可扩展性。新兴的解决方案集中于基因-酶混合平台和个性化再生方法的智能响应系统。生物学原理与材料科学的协同整合为开发下一代治疗策略提供了变革性的基础。

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引用次数: 0

D-peptide engineered hydrogel with dual-enzyme-ALA cascades enables multimodal oxygen modulation for self-sustaining EDT-PDT synergy 具有双酶- ala级联的d肽工程水凝胶可实现多模态氧调节，以实现自我维持的EDT-PDT协同作用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-25 DOI: 10.1016/j.bioactmat.2025.12.037

Qi Zhang , Zhe Zheng , Yiting Zhao , Qing Wu , Chu Wu , Xiuli Wang , Xia Wang , Qigang Wang , Peiru Wang

The transformation of O₂ is primarily facilitated by the catalytic action of redox enzymes, which play a pivotal role in sustaining cellular energy metabolism and redox balance. Bioinspired by O₂ distribution and ROS regulation related to cascade biocatalytic process, a D-peptide NapG^DF^DF^DY engineered hydrogel has been constructed with encapsulated dual-enzyme superoxide (SOD) and chloroperoxidase (CPO) cascade catalytic circuit and co-assembled photosensitizer of 5-aminolevulinic acid molecules (ALA). Multimodal oxygen modulation has been conducted by the concurrent oxygen generation via SOD-catalyzed ⋅O₂⁻ dismutation and oxygen consumption for ¹O₂ production by CPO and ALA, achieving self-sustaining enzymatic dynamic therapy (EDT)-photodynamic therapy (PDT) (EDT-PDT) synergy. The endogenous cascade-amplified EDT not only enhances the ¹O₂ efficacy in exogenous PDT therapy, but the intermediate O₂ can also alleviate local neuropathic pain caused by hypoxia for safe PDT treatment. This work pioneers enzyme-mediated dynamic control of tumor redox homeostasis, establishing a new therapeutic axis between biocatalytic amplification and photodynamic processes.

O2的转化主要是通过氧化还原酶的催化作用来实现的，氧化还原酶在维持细胞能量代谢和氧化还原平衡中起着关键作用。受级联生物催化过程中O2分布和ROS调控的启发，利用双酶超氧化物（SOD）和氯过氧化物酶（CPO）级联催化回路和5-氨基乙酰丙酸分子（ALA）共组装光敏剂，构建了d肽NapGDFDFDY工程水凝胶。多模态氧调制是通过sod催化的⋅O2−突变和CPO和ALA产生1O2的耗氧同时产生氧气，实现自我维持的酶动力治疗（EDT）和光动力治疗（PDT）（EDT-PDT）协同作用。内源性级联扩增的EDT不仅增强了1O2在外源性PDT治疗中的疗效，而且中间O2还可以减轻缺氧引起的局部神经性疼痛，安全进行PDT治疗。这项工作开创了酶介导的肿瘤氧化还原稳态动态控制，在生物催化放大和光动力过程之间建立了新的治疗轴。

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引用次数: 0

Artificial Intelligence Virtual Organoids (AIVOs) 人工智能虚拟类器官

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.030

Long Bai , Jiacan Su

Organoid platforms have reshaped in vitro human biology yet remain constrained by batch variability, sparse longitudinal readouts and barriers to scale. This review introduces Artificial Intelligence Virtual Organoids (AIVOs), also termed silicon organoids: organoid-scale digital twins instantiated in the computational space, with virtual cells-and, where appropriate, virtual organoids-serving as the minimal executable units. AIVOs fuse multimodal and longitudinal measurements into universal state representations and use virtual instruments constrained by biophysical priors to emulate assays and perturbations, while hybrid mechanistic modules (agent-based, continuum, finite-element) capture cell-cell, cell-matrix and transport dynamics. The article defines conceptual boundaries, formalizes a data-model-interaction architecture and construction strategies, and synthesizes evaluation and standardization practices. Applications span drug screening and dosing design, disease subtyping and resistance mapping, integration with organoid-on-chip systems and clinical decision support. Principal challenges include the acquisition and harmonization of high-quality longitudinal data, scalable computation and model reduction, interpretability and causal reasoning, and governance addressing privacy, safety and fairness. Virtual organoids ultimately provide a silicon-grounded, transparent and reproducible bridge between physical organoids and clinical practice, enabling high-throughput in silico experiments and active experiment design without added experimental burden and accelerating precise therapy, mechanism discovery and regulatory translation.

类器官平台已经重塑了体外人类生物学，但仍然受到批量可变性、稀疏的纵向读数和规模障碍的限制。这篇综述介绍了人工智能虚拟类器官（AIVOs），也被称为硅类器官：在计算空间中实例化的类器官尺度数字双胞胎，其中虚拟细胞和虚拟类器官作为最小的可执行单元。AIVOs将多模态和纵向测量融合到通用状态表示中，并使用受生物物理先验约束的虚拟仪器来模拟分析和扰动，而混合机制模块（基于代理的、连续体的、有限元的）捕获细胞-细胞、细胞-矩阵和运输动力学。本文定义了概念边界，形式化了数据模型交互体系结构和构建策略，并综合了评估和标准化实践。应用范围包括药物筛选和剂量设计、疾病亚型和耐药性制图、与类器官芯片系统的集成以及临床决策支持。主要挑战包括获取和协调高质量的纵向数据、可扩展计算和模型缩减、可解释性和因果推理，以及解决隐私、安全和公平问题的治理。虚拟类器官最终在物理类器官和临床实践之间提供了一个硅基、透明和可重复的桥梁，实现了高通量的硅实验和主动实验设计，而不增加实验负担，加速了精确治疗、机制发现和调控转化。

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引用次数: 0

Engineered small extracellular vesicles as bioactive materials: Integrating engineering strategies for cargo loading and targeted delivery systems 工程小细胞外囊泡作为生物活性材料：货物装载和目标递送系统的整合工程策略

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.029

Hongtao Xu , Rui Liu , Hao Zhou , Bin Kong , Kai Shen , Tao Zhao , Xiaofeng Du , Hao Zhang , Huanghe Song , Dunming Guo , Xiaoyuan Gu , Qing Wang , Chien-Wei Lee , Guoyong Yin , Yingze Zhang , Wei Chen

Small extracellular vesicles (sEVs) are increasingly regarded as a unique class of bioactive materials whose intrinsic membrane composition and nanoscale architecture provide a versatile platform for therapeutic engineering. Rather than passive carriers, sEVs can be actively programmed through diverse strategies to achieve efficient loading, precise targeting, and functional integration with synthetic systems. Endogenous modulation of donor cells—via genetic editing, priming with bioactive glass, cytokine stimulation, or hypoxic cues—enables selective packaging of nucleic acids, proteins, and metabolites into secreted vesicles. Exogenous techniques, including electroporation, sonication, and extrusion, allow controlled incorporation of therapeutic drugs or genome-editing complexes such as CRISPR/Cas. In parallel, surface modifications based on Lamp2b-fusion scaffolds, aptamers, antibodies, and click chemistry confer tissue tropism and extend circulation time. Integration with nanomaterials, scaffolds, and microfluidic platforms further enhances stability, scalability, and reproducibility, positioning sEVs at the intersection of biology and materials science. This review highlights recent advances in engineering sEVs as programmable bioactive materials and discusses their potential to transform regenerative medicine, oncology, and precision therapeutics.

小细胞外囊泡（sev）越来越被认为是一类独特的生物活性材料，其固有的膜组成和纳米级结构为治疗工程提供了一个多功能平台。与被动载体不同，sev可以通过多种策略进行主动编程，以实现高效装载、精确定位以及与合成系统的功能集成。供体细胞的内源性调节——通过基因编辑、生物活性玻璃启动、细胞因子刺激或缺氧提示——能够选择性地将核酸、蛋白质和代谢物包装到分泌的囊泡中。外源性技术，包括电穿孔、超声和挤压，允许治疗药物或基因组编辑复合物（如CRISPR/Cas）的可控结合。同时，基于lamp2b融合支架、适体、抗体和click化学的表面修饰赋予组织亲和性并延长循环时间。与纳米材料、支架和微流控平台的集成进一步增强了sev的稳定性、可扩展性和可重复性，使其处于生物学和材料科学的交叉点。本文重点介绍了工程sev作为可编程生物活性材料的最新进展，并讨论了它们在再生医学、肿瘤学和精确治疗方面的潜力。

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引用次数: 0

Nanocatalytic magnesium osteoimplants with biodegradable self-adaptive interfaces for therapeutic repair of infected bone defects 具有可生物降解自适应界面的纳米催化镁骨植入物用于感染性骨缺损的治疗性修复

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.018

Yuanyuan Wu , Zhe Cai , Yuling Zhang , Yufeng Zheng , Liqiong Liao , Zhaojun Jia

Infected bone defects (e.g., osteomyelitis) present a complex clinical challenge characterized by persistent biofilms, intracellular pathogens, and compromised bone regeneration. We hypothesized that a bioadaptive magnesium implant with sequential coating/substrate degradation could render staged anti-infective and pro-regenerative therapy. To this end, we engineered TNE@AHA_C implants consisting of a Mg–Zn alloy substrate functionalized with a multilayered coating: a corrosion-resistant MgF₂ underlayer, a polydopamine/polyethyleneimine adhesive interlayer, and an infection-responsive aldehyde-modified hyaluronic acid (AHA) hydrogel toplayer embedded with microbe-targeting Fe₃O₄ nanozymes (TNE). The implants demonstrated improved hydrophilicity and corrosion resistance and time-sequenced coating/substrate degradation. In infectious microenvironments, the TNE-embedded coating degraded preferentially, releasing nanozymes that catalytically generated bactericidal hydroxyl radicals to eradicate planktonic bacteria, intracellular pathogens, and biofilms, while stimulating M1 macrophage polarization for enhanced immunobactericidal activity. Subsequently, controlled substrate corrosion released bioactive ions (Mg²⁺, Zn²⁺) and H₂, which elicited M2 macrophage polarization and osteodifferentiation, while allowing favorable biocompatibility in vitro, in ovo, and in vivo. In a Staphylococcus aureus-infected rat femoral model, TNE@AHA_C effectively eliminated infection, mitigated inflammation and osteolysis, and enhanced osteoregeneration/osseointegration. This work establishes a sequential degradation-driven bioadaptive paradigm for implant-mediated microenvironment remodeling in infectious bone defects.

感染性骨缺损（如骨髓炎）呈现出复杂的临床挑战，其特征是持续的生物膜、细胞内病原体和骨再生受损。我们假设生物适应性镁植入物具有顺序涂层/底物降解可以实现分阶段抗感染和促再生治疗。为此，我们设计了TNE@AHAC植入物，该植入物由多层涂层功能化的Mg-Zn合金衬底组成：耐腐蚀的MgF2衬底，聚多巴胺/聚乙烯亚胺粘合剂中间层，感染反应醛修饰透明质酸（AHA）水凝胶，嵌入微生物靶向Fe3O4纳米酶（TNE）。植入物表现出更好的亲水性和耐腐蚀性以及按时间顺序的涂层/衬底降解。在感染性微环境中，嵌入tne的涂层优先降解，释放纳米酶，催化产生杀菌羟基自由基，消灭浮游细菌、细胞内病原体和生物膜，同时刺激M1巨噬细胞极化，增强免疫杀菌活性。随后，受控的底物腐蚀释放出生物活性离子（Mg2+、Zn2+）和H2，诱导M2巨噬细胞极化和骨分化，同时在体外、卵内和体内均具有良好的生物相容性。在金黄色葡萄球菌感染的大鼠股骨模型中，TNE@AHAC有效消除感染，减轻炎症和骨溶解，增强骨再生/骨整合。这项工作为感染性骨缺损中植入物介导的微环境重塑建立了一个顺序降解驱动的生物适应范式。

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