Bioactive Materials最新文献_第3页

Integrated fabrication of a shape-adaptable, antioxidative composite stent for effective closure and biological repair of enteroatmospheric fistula 一种形状适应性、抗氧化复合支架的集成制造，用于有效闭合和生物修复肠大气瘘

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-20 DOI: 10.1016/j.bioactmat.2026.01.014

Guiwen Qu , Ze Li , Shuanghong Yang , Luqiao Huang , Ye Liu , Sicheng Li , Juanhan Liu , Lili Yu , Rui Ma , Yitian Teng , Haohui Li , Jinjian Huang , Jianan Ren , Xiuwen Wu

Enteroatmospheric fistulas (EAFs) pose significant clinical challenges due to persistent leakage, inflammation, and impaired epithelial repair. Transcriptomic analyses of fistula tissues reveal elevated oxidative stress, mitochondrial dysfunction, and barrier disruption. Current provisional closure devices lack adaptability to complex fistula anatomy and fail to provide bioactive support, limiting tissue repair. Here, we report a body-temperature-responsive shape memory polymer stent coated with a bioactive hydrogel, fabricated through an integrated process, for effective EAF closure and repair. The stent can be delivered in a compact state and self-deployed in vivo, ensuring minimally invasive implantation and conformal closure. The composite stent enhances epithelial cell migration, attenuates oxidative stress, and alleviates inflammation, thereby establishing a microenvironment that promotes repair. In rabbit EAF models, the composite stent effectively closed the fistula, improved nutritional status, restored epithelial integrity, reduced inflammation, and enhanced goblet cell regeneration. Transcriptomic profiling and pathway validation revealed activation of oxidative phosphorylation, HIF-1, PI3K-Akt signaling, tight junction, and mucosal immune pathways, highlighting restoration of redox balance, mitochondrial metabolism, barrier integrity, and immune defense. These findings demonstrate that integrating dynamic shape adaptability with bioactive functionality can promote both physical closure and biological repair. This strategy provides a generalizable platform for treating complex epithelial defects in gastrointestinal organs.

肠大气瘘（EAFs）由于持续渗漏、炎症和上皮修复受损，给临床带来了重大挑战。瘘组织的转录组学分析显示氧化应激升高，线粒体功能障碍和屏障破坏。目前的临时封闭装置缺乏对复杂瘘管解剖结构的适应性，不能提供生物活性支持，限制了组织修复。在这里，我们报道了一种覆盖生物活性水凝胶的体温响应形状记忆聚合物支架，通过集成工艺制造，用于有效的EAF闭合和修复。该支架能以致密状态输送，在体内自我展开，确保微创植入和适形闭合。复合支架增强上皮细胞迁移，减轻氧化应激，减轻炎症，从而建立促进修复的微环境。在家兔EAF模型中，复合支架有效关闭瘘管，改善营养状况，恢复上皮完整性，减少炎症，促进杯状细胞再生。转录组学分析和途径验证显示，氧化磷酸化、HIF-1、PI3K-Akt信号、紧密连接和粘膜免疫途径的激活，突出了氧化还原平衡、线粒体代谢、屏障完整性和免疫防御的恢复。这些发现表明，将动态形状适应性与生物活性功能相结合可以促进物理闭合和生物修复。该策略为胃肠道器官复杂上皮缺陷的治疗提供了一个可推广的平台。

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引用次数: 0

Bioactive-coated porous anastomotic staples enhance anastomotic healing 生物活性涂层多孔吻合器促进吻合口愈合

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-20 DOI: 10.1016/j.bioactmat.2026.01.005

Renjie Li , Qi Sun , Ruijun Xu , Runlong Zhu , Jiarui Lin , Qijing Tang , Qihuan Zhou , Yong Li , Feng Wang , Zifeng Yang

Titanium (Ti) staples used for digestive tract reconstruction often suffer from delayed anastomotic healing and increased complication rate due to insufficient surface bioactivity. In this study, we combine a micro/nano porous Ti (Ti-OH) with an electrochemically co-deposited polydopamine (PDA) bioactive coating to construct vascular endothelial growth factor (VEGF) high loading and stage-adaptive release staples (Ti-OH-ePV). Alkali heat treatment generates hydroxyl groups and a micro/nano porous structure on the surface of Ti staples, which enhances the combination between the coating and the Ti-OH, increasing the loading capacity for VEGF. Electrochemical co-deposition embeds VEGF within the PDA network, further improving VEGF loading. Importantly, the PDA coating exhibits pH-responsive release, enabling a rapid release of VEGF under the acidic microenvironment of the inflammatory phase, thereby inducing angiogenesis and promoting macrophage polarization toward the M2 phenotype. During the subsequent proliferative phase, the sustained release of VEGF continuously drives vascular network formation, while the exposed porous structure further enhances cell migration and proliferation, synergistically promoting anastomotic healing. In a rabbit gastrointestinal anastomosis model, the Ti-OH-ePV significantly increased anastomotic bursting pressure, reduced inflammatory cytokine levels, enhanced neovascularization, and improved collagen organization, indicating markedly improved healing quality. Collectively, this study offers a theoretical basis and technical support for the development of phase-adaptive tissue repair materials.

用于消化道重建的钛（Ti）钉由于其表面生物活性不足，往往存在吻合口愈合延迟和并发症发生率增高的问题。在这项研究中，我们将微纳米多孔钛（Ti- oh）与电化学共沉积聚多巴胺（PDA）生物活性涂层结合，构建血管内皮生长因子（VEGF）高负荷和阶段自适应释放钉（Ti- oh - epv）。碱热处理在钛钉表面生成羟基和微纳多孔结构，增强了涂层与Ti- oh的结合，增加了VEGF的负载能力。电化学共沉积将VEGF嵌入到PDA网络中，进一步提高了VEGF的负载。重要的是，PDA涂层表现出ph响应性释放，使VEGF在炎症期的酸性微环境下快速释放，从而诱导血管生成，促进巨噬细胞向M2表型极化。在随后的增殖期，VEGF的持续释放不断推动血管网络的形成，而暴露的多孔结构进一步增强了细胞的迁移和增殖，协同促进吻合口愈合。在兔胃肠吻合模型中，Ti-OH-ePV显著提高吻合口破裂压力，降低炎症细胞因子水平，促进新生血管形成，改善胶原组织，表明愈合质量明显提高。本研究为相适应组织修复材料的开发提供了理论基础和技术支持。

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引用次数: 0

Thermosensitive citrate-based mussel-inspired attack-defense integrated bioadhesives facilitate complicated wound healing 热敏柠檬酸盐为基础的贻贝启发的攻击防御集成生物粘合剂促进复杂的伤口愈合

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-20 DOI: 10.1016/j.bioactmat.2026.01.010

Meimei Fu , Qiankun Shi , Yitao Zhao , Jintao Li , Zhuoyi Huang , Zhihui Lu , Jian Yang , Dongfang Zhou , Jinshan Guo

The treatment of complicated wounds remains unsatisfactory due to the lack of a comprehensive strategy synchronously addressing concomitant disease cure along with favorable wound healing. Herein, a family of thermosensitive citrate-based mussel-inspired bioadhesives (TCMBAs) were developed for the first time by mixing poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)-incorporated and calcium-containing water-soluble injectable citrate-based mussel-inspired bioadhesive prepolymer with FeCl₃ in bicine solution. With a tunable minimum sol-to-gel transition temperature in the range of 28–42 °C, the optimized TCMBAs can be conveniently administrated at room temperature and instantly close wounds at body temperature. TCMBAs exhibit a suite of ideal material properties, including high wet tissue adhesion strength, rapid shape adaptability, self-healing capability, and high elasticity. Furthermore, they demonstrate fast biodegradability, excellent biocompatibility, and potent hemostatic ability. The intrinsic photothermal conversion efficiency of TCMBAs facilitates mild photothermal therapy (PTT), inducing a thermo-mediated cytotoxic effect that effectively eliminates both pathogenic bacteria and cancer cells. This multifunctional “attack–defense” property, combining antimicrobial and antitumor effects with barrier protection and regenerative functions, was demonstrated in infected and cancerous wound models. TCMBA-based treatment under NIR irradiation promoted healing of infected wounds and suppressed tumor recurrence and metastasis while accelerating wound closure. These results highlight TCMBAs as a highly promising platform for the treatment of complex and refractory wounds.

复杂伤口的治疗仍然不令人满意，因为缺乏一个全面的策略，同时解决伴随疾病的治愈和良好的伤口愈合。本文首次将聚（乙二醇）-嵌段聚（丙二醇）-嵌段聚（乙二醇）-含钙水溶性可注射柠檬酸基贻贝生物胶预聚体与FeCl3混合在bicine溶液中，开发了一类热敏型柠檬酸基贻贝生物胶（tcbas）。优化后的tcmba具有28-42℃的最低溶胶-凝胶转变温度，可以方便地在室温下给药，并在体温下立即闭合伤口。tcba具有一系列理想的材料特性，包括高湿组织粘附强度、快速形状适应性、自修复能力和高弹性。此外，它们具有快速的生物降解性、良好的生物相容性和强大的止血能力。tcba固有的光热转换效率促进轻度光热治疗（PTT），诱导热介导的细胞毒性作用，有效地消除致病菌和癌细胞。这种多功能“攻防”特性，结合了抗菌和抗肿瘤作用以及屏障保护和再生功能，已在感染和癌变伤口模型中得到证实。近红外照射下以tcmba为基础的治疗可促进感染创面愈合，抑制肿瘤复发和转移，加速创面愈合。这些结果突出了tcm作为治疗复杂和难治性伤口的一个非常有前途的平台。

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引用次数: 0

Synergistic targeting of senolytic and senomorphic action with dual-engineered biomimetic macrophage nanovesicles for mitigating osteoarthritis 双工程仿生巨噬细胞纳米囊泡对骨关节炎的抗衰老和同源作用的协同靶向作用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-19 DOI: 10.1016/j.bioactmat.2025.11.047

Wenan Peng , Ziming Wang , Zenan Zhuang , Simin Zeng , Yu Xia , Qiwen Chen , Xuan Bai , Ying Tang , Cui Huang , Xianzheng Zhang

Osteoarthritis (OA), a leading cause of chronic disability worldwide, is increasingly recognized to be driven by the accumulation of senescent chondrocytes (sCDs) and their deleterious pro-inflammatory senescence-associated secretory phenotype (SASP). Existing therapies, including senolytics and senomorphics, lack cell-specific targeting and fail to neutralize the heterogeneous components of SASP. Here, we develop a dual-engineered macrophage membrane camouflaged, self-assembled nanoplatform (BS@MD) that combines senolytic and senomorphic functions synergistically. Within the OA microenvironment, BS@MD acts as a “nanosponge” to broadly neutralize SASP through overexpressed cytokine receptors derived from LPS-primed macrophage membranes. This process alleviates chondrocyte senescence and facilitates the phenotypic shift of pro-inflammatory M1 macrophages toward an anti-inflammatory M2 state. Additionally, surface conjugation with an anti-DPP4 antibody enables BS@MD to selectively target sCDs and disassemble in the acidic lysosomal environment, releasing bortezomib (BTZ) and sabutoclax (Sab). These agents act synergistically to inhibit the NF-κB and BCL-2 pathways, thereby inducing sCDs apoptosis and suppressing SASP production, effectively disrupting the senescence-inflammation feedback loop. In the anterior cruciate ligament transection (ACLT)-induced OA mouse model and naturally aged OA mouse model, BS@MD enhances joint retention, reduces cartilage degradation and inflammation, and promotes cartilage homeostasis. Overall, this work pioneers a dual-pronged senotherapeutic strategy for non-surgical OA management.

骨关节炎（OA）是世界范围内慢性残疾的主要原因，越来越多的人认识到是由衰老软骨细胞（sCDs）的积累及其有害的促炎衰老相关分泌表型（SASP）驱动的。现有的治疗方法，包括senolytics和senomorphics，缺乏细胞特异性靶向，不能中和SASP的异质成分。在这里，我们开发了一种双工程巨噬细胞膜伪装、自组装的纳米平台（BS@MD），它协同结合了衰老和同形功能。在OA微环境中，BS@MD作为“纳米海绵”，通过lps引发的巨噬细胞膜中过度表达的细胞因子受体广泛中和SASP。这一过程缓解了软骨细胞衰老，促进促炎M1巨噬细胞向抗炎M2状态的表型转变。此外，与抗dpp4抗体的表面结合使BS@MD能够选择性地靶向sCDs并在酸性溶酶体环境中分解，释放硼替佐米（BTZ）和sabutoclax （Sab）。这些药物协同作用，抑制NF-κB和BCL-2通路，从而诱导sCDs凋亡，抑制SASP的产生，有效地破坏衰老-炎症反馈回路。在前交叉韧带横断（ACLT）诱导的OA小鼠模型和自然衰老OA小鼠模型中，BS@MD增强关节潴留，减少软骨退化和炎症，促进软骨稳态。总的来说，这项工作开创了非手术OA管理的双管齐下的老年治疗策略。

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引用次数: 0

Exosome-functionalized photocrosslinked GelMA/HAMA hydrogel promotes facial nerve recovery via inflammatory microenvironment regulation 外泌体功能化光交联GelMA/HAMA水凝胶通过炎症微环境调节促进面神经恢复

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-19 DOI: 10.1016/j.bioactmat.2026.01.008

Chun Chen , Yifei Zhang , Linchao Zhang , Israr Ullah , Lei Hang , Yupeng Liu , Jun Yang

Facial nerve crush injuries frequently lead to incomplete functional restoration owing to constrained regenerative approaches and suboptimal treatment methods. While hydrogel-based systems have emerged as viable alternatives among bioengineered scaffolds, their therapeutic potential remains compromised by inadequate biological activity and unfavorable inflammatory conditions. Our research engineered a photoactivated GelMA/HAMA composite hydrogel incorporating bone marrow mesenchymal stem cell-derived exosomes (BExos), with comprehensive characterization of its material attributes. We systematically assessed the biomaterial's regenerative capacity through in vitro experiments involving BMSCs and RAW264.7 macrophages, complemented by comprehensive in vivo evaluations in a rodent facial nerve injury model incorporating functional restoration metrics, neurophysiological testing, tissue analysis, and biomolecular profiling. The BExos-integrated hydrogel established a favorable niche promoting BMSCs transdifferentiation toward Schwann cell-mimetic lineages while demonstrating marked improvement in neuromuscular functional restoration. Compared to untreated cohorts, the composite hydrogel demonstrated enhanced axonal regrowth, improved remyelination processes, and notably reduced oxidative damage. The biomaterial effectively shifted macrophage differentiation from M1 pro-inflammatory states toward M2 anti-inflammatory phenotypes through modulation of PI3K/NF-κB/P38 signaling cascades, with Neuronatin emerging as a key regulatory element in this pathway. Mechanistic investigations demonstrated that the therapeutic benefits stemmed from synergistic structural reinforcement combined with exosome-mediated immune regulation, positioning this dual-action hydrogel as an innovative solution for facial nerve repair.

面神经挤压伤由于再生途径的限制和治疗方法的不理想，经常导致功能恢复不完全。虽然基于水凝胶的系统已经成为生物工程支架中可行的替代品，但其治疗潜力仍然受到生物活性不足和不利炎症条件的影响。我们的研究设计了一种含有骨髓间充质干细胞衍生外泌体（BExos）的光激活GelMA/HAMA复合水凝胶，并对其材料属性进行了全面表征。我们通过BMSCs和RAW264.7巨噬细胞的体外实验，系统地评估了生物材料的再生能力，并在啮齿动物面神经损伤模型中进行了全面的体内评估，包括功能恢复指标、神经生理测试、组织分析和生物分子分析。整合bexos的水凝胶建立了一个有利的生态位，促进骨髓间充质干细胞向模拟雪旺细胞谱系的转分化，同时显示出神经肌肉功能恢复的显著改善。与未治疗的队列相比，复合水凝胶表现出增强的轴突再生，改善的髓鞘再生过程，并显著减少氧化损伤。这种生物材料通过调节PI3K/NF-κB/P38信号级联，有效地将巨噬细胞从M1促炎状态转变为M2抗炎表型，而Neuronatin是这一途径中的关键调控元件。机制研究表明，治疗益处源于协同结构强化结合外泌体介导的免疫调节，将这种双作用水凝胶定位为面神经修复的创新解决方案。

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引用次数: 0

NsPEFs-enriched ADSCs-EVs alleviate osteoarthritis via RSPO3-mediated dual pro-chondrogenic and pro-M2 macrophage properties nspef富集的adscs - ev通过rspo3介导的双促软骨生成和促m2巨噬细胞特性缓解骨关节炎

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-17 DOI: 10.1016/j.bioactmat.2026.01.006

Yushan Wang , Yingjie Gao , Zhiyan Cao , Mingjie Dong , Pengfei Shao , Hao Fan , Zijian Guo , Xiaoyong Hu , Wenxiang Cheng , Pengcui Li , Wei Zhang , Yi Feng , Panfeng Fu , Zigang Ge , Jiake Xu , Chuan Xiang

Osteoarthritis (OA) remains a debilitating joint disorder due to the lack of disease-modifying therapies that can simultaneously halt cartilage degradation and modulate the aberrant immune microenvironment. This study demonstrated the therapeutic potential of extracellular vesicles derived from adipose-derived stem cells preconditioned with nanosecond pulsed electric fields (NsPEFs-ADSCs-EVs). Administration of NsPEFs-ADSCs-EVs significantly attenuated OA progression, as indicated by alleviated cartilage degradation, and a marked shift in synovial macrophage from the pro-inflammatory M1 to the pro-reparative M2 phenotype.

Mechanistically, we discovered that NsPEFs-ADSCs-EVs, via surface-enriched ITGA4, activated the PI3K/Akt pathway to instruct the increased secretion of R-spondin 3 (RSPO3). We further unveiled a novel dual function of chondrocyte-derived RSPO3. It acted in an autocrine manner to enhance chondrocyte anabolism and in a paracrine manner to directly drive M2 macrophage polarization. The pro-M2 effect was specifically mediated through the activation of the LGR4/LRP6/β-catenin signaling axis in macrophages.

Collectively, this work elucidates a previously unrecognized paracrine axis wherein NsPEFs-engineered EVs deploy RSPO3 as a significant coordinator to synchronously promote cartilage regeneration and immune resolution. Our findings not only reveal RSPO3 as a promising therapeutic target but also establish the NsPEFs platform as a efficient strategy for generating functionally enhanced EVs, offering a novel cell-free strategy for OA therapy.

骨关节炎（OA）仍然是一种使人衰弱的关节疾病，因为缺乏能够同时阻止软骨降解和调节异常免疫微环境的疾病修饰疗法。本研究证实了纳秒脉冲电场预处理脂肪干细胞的细胞外囊泡的治疗潜力。nspef - adscs - ev可显著减缓骨性关节炎的进展，这可以通过软骨退化的缓解和滑膜巨噬细胞从促炎M1表型向促修复M2表型的显著转变来证明。在机制上，我们发现nspef - adscs - ev通过表面富集的ITGA4激活PI3K/Akt通路，指导R-spondin 3 （RSPO3）的分泌增加。我们进一步揭示了软骨细胞衍生的RSPO3的一种新的双重功能。它以自分泌方式增强软骨细胞合成代谢，并以旁分泌方式直接驱动M2巨噬细胞极化。巨噬细胞通过激活LGR4/LRP6/β-catenin信号轴特异性介导pro-M2效应。总的来说，这项工作阐明了一个以前未被认识到的旁分泌轴，其中nspef工程的ev将RSPO3作为一个重要的协调者，同步促进软骨再生和免疫分解。我们的研究结果不仅揭示了RSPO3是一个有希望的治疗靶点，而且还建立了NsPEFs平台作为产生功能增强的ev的有效策略，为OA治疗提供了一种新的无细胞策略。

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引用次数: 0

Outside Back Cover 外封底

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-14 DOI: 10.1016/S2452-199X(25)00603-6

引用次数: 0

Monocyte/macrophage-mediated trained immunity in disease prevention and immunotherapy 单核细胞/巨噬细胞介导的训练免疫在疾病预防和免疫治疗中的应用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-12 DOI: 10.1016/j.bioactmat.2025.12.044

Xiao Zhang , Xinlian Wang , Miaomiao Xu , Jing Yuan , Ying Liu

Trained immunity refers to a functional reprogramming of the innate immune system that enhances its ability to respond to secondary stimuli. Monocytes and macrophages are central effectors of innate immunity with broad therapeutic relevance. Their capacity to acquire trained immunity enhances host defense and shapes immune homeostasis through epigenetic, metabolic, and functional changes. Unlike previous reviews that primarily focus on molecular mechanisms or vaccine-induced training, this review emphasizes the distinct roles of monocyte/macrophage-mediated trained immunity, originating from both central and peripheral sources. We further discuss how nanomaterials can be harnessed to precisely modulate this process, offering new opportunities for infection control, tumor immunotherapy, and the regulation of chronic inflammatory diseases. This dual-perspective framework provides a foundation for translating trained immunity into targeted clinical interventions.

训练免疫是指先天免疫系统的功能性重新编程，增强其对二次刺激的反应能力。单核细胞和巨噬细胞是先天免疫的中心效应细胞，具有广泛的治疗意义。它们获得训练免疫的能力通过表观遗传、代谢和功能变化增强宿主防御和塑造免疫稳态。与以往主要关注分子机制或疫苗诱导训练的综述不同，本综述强调单核细胞/巨噬细胞介导的训练免疫的独特作用，源自中央和外周来源。我们进一步讨论了如何利用纳米材料来精确调节这一过程，为感染控制、肿瘤免疫治疗和慢性炎症性疾病的调节提供新的机会。这种双重视角框架为将经过训练的免疫转化为有针对性的临床干预提供了基础。

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 : 2026-01-10 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。

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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 : 2026-01-10 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。

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引用次数: 0