Bioactive Materials最新文献_第7页

Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtDNA IPFP-MSCs的细胞外囊泡通过转移mtDNA引发骨关节炎

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-11 DOI: 10.1016/j.bioactmat.2025.11.046

Shiyu Li , Zi Yan , Xinwang Zhi , Weihan Zheng , Ziqi Zhang , Zhenning Dai , Wanying Chen , Hui Lu , Ziyi Feng , Ting Cheng , Wenhui Liu , Baoyu Sun , Yuhai Ma , Bing Zhang , Jianyuan Zhao , Han Liu , Jiacan Su

Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) extracellular vesicles (EVs) are found to be capable of accelerating Osteoarthritis (OA) progression. However, which pathways and which pathogenic EVs subgroups are involved are not defined. In our study we found that there were a higher percentage of TOMM20⁺ EV's within the total synovial fluid EV's from OA patients than from trauma patients as well as increased mtDNA content. This implicates the mitochondria derived EV sub-group - mitochondria derived vesicles (MDVs) as a potential driver in OA. We found with the single-cell data that MDVs may be secreted from IPFP-MSCs with VPS35. Furthermore, these cells were harvested from the body of the OA patient. IPFP-MSC derived MDVs can deliver exogenous mtDNA to chondrocytes by fusing directly, thus inhibiting chondrocyte matrix synthesis, inducing mitochondrial dysfunction, and activating pro-inflammatory signaling cascades in chondrocytes. Protein microarrays showed that MDVs delivered exogenous mtDNA to chondrocytes, which then activated the cGAS-STING pathway and downstream inflammatory mediators (TBK1, NF-κB, TNF-α). Intra-articular MDV injection worsened cartilage degradation and synovitis in OA rats but STING inhibition alleviated them. This study showed that IPFP-MSC-derived MDVs are essential for OA pathogenesis via mtDNA transfer and cGAS-STING pathway activation. These results show how the mitochondria and immune system talk to each other in the joints causing pain and destroying the cartilage, MDVs are new things that can tell us if someone has this disease and help doctors fix it. Pharmacological blockade of the cGAS-STING axis has shown therapeutic potential, providing a dual approach to mitigate mitochondrial stress and innate immune hyperactivation in OA.

髌下脂肪垫间充质干细胞（IPFP-MSCs）细胞外囊泡（ev）被发现能够加速骨关节炎（OA）的进展。然而，涉及哪些途径和哪些致病性ev亚群尚未确定。在我们的研究中，我们发现OA患者的总滑液EV中TOMM20+ EV的百分比高于创伤患者，并且mtDNA含量增加。这暗示线粒体来源的EV亚群-线粒体来源的囊泡（mdv）是OA的潜在驱动因素。我们通过单细胞数据发现，mpv可能从IPFP-MSCs中分泌。此外，这些细胞来自OA患者的身体。IPFP-MSC衍生的mdv可以通过直接融合将外源mtDNA传递到软骨细胞，从而抑制软骨细胞基质合成，诱导线粒体功能障碍，激活软骨细胞内促炎信号级联反应。蛋白质微阵列显示，mdv将外源性mtDNA传递到软骨细胞，然后激活cGAS-STING途径和下游炎症介质（TBK1, NF-κB, TNF-α）。关节内注射MDV加重OA大鼠软骨退化和滑膜炎，抑制STING可减轻软骨退化和滑膜炎。本研究表明ipfp - msc衍生的mdv通过mtDNA转移和cGAS-STING通路激活对OA发病至关重要。这些结果表明，线粒体和免疫系统如何在关节中相互交流，导致疼痛并破坏软骨，mdv是一种新的东西，可以告诉我们是否有人患有这种疾病，并帮助医生治疗它。药物阻断cGAS-STING轴已显示出治疗潜力，提供了一种双重途径来减轻OA的线粒体应激和先天免疫过度激活。

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引用次数: 0

EDAC-mediated O-acylisourea rearrangement for tertiary amine cationization of hyaluronic acid (HA) and its application as structural backbones in virus-inspired polyplexes edac介导的o -酰基异脲重排对透明质酸（HA）叔胺阳离子化及其在病毒激发多聚体中作为结构主干的应用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-11 DOI: 10.1016/j.bioactmat.2025.12.012

Yinghao Li , Liang Yao , Jiahao Liu , Yi Situ , Chunyu Zhao , Tianyu Mao , Xi Wang , Rijian Song , Hongyun Tai , Zhonglei He , Jing Lyu , Wenxin Wang

Cationic modification of hyaluronic acid (HA) is challenging due to its polyanionic nature, poor reactivity in water, and the instability of conventional coupling intermediates. This limits the development of HA-based components in non-viral gene delivery systems, which already suffer from amorphous morphology and mechanical fragility that reduce their transfection efficiency. Here, we reprogram a classically unfavorable EDAC-mediated rearrangement into a productive synthetic route, enabling direct cationization of hyaluronic acid (HA) through spontaneous O-acylisourea rearrangement. This water-based, catalyst-free process achieves up to 70 % substitution of HA's carboxyl groups—introducing cationic tertiary amine functionalities in water. The resulting aminated-hyaluronic acid (HAA) scaffolds act as rigid structural backbones in virus-inspired polymer–DNA nanoparticles termed as “Skeletoplexes”, with enhanced stability and performance. When incorporated into polyplexes formed from diverse cationic systems—including poly(β-amino esters) and commercial vectors such as BrPERfect, Xfect, jetPEI, and Lipofectamine3000—HAA scaffolds improved in vitro transfection efficiency by up to 4-fold and in vivo gene expression by approximately 2-fold. These results establish a generalizable and green scaffold-based strategy that bridges the structural and functional gap between viral and non-viral gene delivery vectors.

透明质酸（HA）的阳离子改性具有挑战性，因为它的多阴离子性质，在水中的反应性差，以及传统偶联中间体的不稳定性。这限制了在非病毒基因传递系统中基于ha的组件的发展，这些组件已经受到无定形形态和机械脆弱性的影响，降低了它们的转染效率。在这里，我们将传统上不利的edac介导的重排重新编程为高效的合成路线，通过自发的o -酰基异脲重排实现透明质酸（HA）的直接阳离子化。这种基于水的，无催化剂的工艺实现了高达70%的HA的羧基取代-在水中引入阳离子叔胺功能。由此产生的氨基透明质酸（HAA）支架在病毒激发的聚合物- dna纳米颗粒（称为“骨架”）中充当刚性结构骨架，具有增强的稳定性和性能。当纳入由不同阳离子体系（包括聚β-氨基酯）和商业载体（如BrPERfect， xeffect， jetPEI和lipofectamine3000）形成的多聚物时，haa支架的体外转染效率提高了4倍，体内基因表达提高了约2倍。这些结果建立了一个可推广的绿色支架策略，在病毒和非病毒基因传递载体之间的结构和功能上架起了桥梁。

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引用次数: 0

Apoptotic metabolites synthesize and inherit unique de novo L2a/L2b RNAs to prevent virus infection 凋亡代谢物合成和遗传独特的新生L2a/L2b rna以防止病毒感染

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-10 DOI: 10.1016/j.bioactmat.2025.11.035

Peiyi Li , Yelin Lan , Xutong Yan , Zeyuan Cao , Jingyun Ji , Mingqiang Deng , Dongmei He , Ruoxin Huang , Yan Qu , Yaoxing Wu , Xinchun Zhang , Jun Cui , Guanzheng Luo , Xichen Bao , Songtao Shi

Apoptosis is indispensable for a variety of physio-pathological processes. RNA is one of essential macromolecules for life. Extensive RNA decay is a characteristic feature of apoptosis. However, it is unknown whether there is de novo RNA synthesis in apoptotic cells and metabolites. In this study, we show that apoptotic mesenchymal stem cells (MSCs) and their apoptotic vesicles (apoVs) synthesize de novo RNAs. Nascent RNA-seq showed apoptotic MSCs and apoVs produced numerous nascent RNAs that were different from those in living MSCs, including protein-coding and non-coding RNAs. Mechanistically, apoptotic de novo RNA synthesis was related to the caspase-3/Sp1/RNA polymerase axis. Additionally, we found the LINE-2a (L2a) and LINE-2b (L2b) RNAs were specifically transcribed in apoptotic MSCs and transferred into apoVs to prevent virus infection. Altogether, this study reveals a previously unknown phenomenon that apoptotic cells synthesize various de novo RNAs and identifies that apoptotic LINE-2 RNAs can regulate innate immunity to prevent virus infection.

细胞凋亡在多种生理病理过程中不可或缺。RNA是生命所必需的大分子之一。广泛的RNA衰变是细胞凋亡的一个特征。然而，凋亡细胞及其代谢产物中是否存在从头RNA合成尚不清楚。在这项研究中，我们发现凋亡的间充质干细胞（MSCs）和它们的凋亡囊泡（apoVs）可以合成新的rna。新生RNA-seq显示凋亡的MSCs和apoVs产生了许多不同于活的MSCs的新生rna，包括蛋白质编码rna和非编码rna。机制上，凋亡新生RNA合成与caspase-3/Sp1/RNA聚合酶轴有关。此外，我们发现LINE-2a （L2a）和LINE-2b (L2b) rna在凋亡的MSCs中特异性转录并转移到apov中以防止病毒感染。总之，本研究揭示了一个以前未知的现象，即凋亡细胞合成各种新生rna，并确定凋亡的LINE-2 rna可以调节先天免疫以预防病毒感染。

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引用次数: 0

Chiral metal nanozyme-enabled SOD2 activation and siRNA delivery cooperatively mitigating chronic heart failure 手性金属纳米酶激活SOD2和siRNA递送协同缓解慢性心力衰竭

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-09 DOI: 10.1016/j.bioactmat.2025.11.049

Zekun Wang , Ruofei Zhang , Yanyu Hu , Qile Song , Xiaoyan Fu , Yifan Wang , Mei Chen , Kelong Fan , Cundong Fan , Dongdong Sun

Doxorubicin (DOX) treatment can lead to intracellular iron overload in cardiomyocytes, triggering excessive generation of reactive oxygen species (ROS) and resulting in cardiotoxicity. Superoxide dismutase (SOD) effectively scavenges ROS, and its catalytic activity depends on the binding of metal ions at its active site. Therefore, enhancing the activity of metal-dependent SOD represents a promising strategy to inhibit ferroptosis in cardiomyocytes and alleviate DOX-induced chronic heart failure. In this study, we constructed a biomimetic chiral MnO₂ nanozyme co-modified with macrophage and platelet membranes (D/L-MnO₂@MM), enabling precise targeting of DOX-injured myocardial tissues. This nanozyme exhibited potent catalase-like and SOD-like activities, efficiently eliminating excessive local hydrogen peroxide (H₂O₂) and superoxide anions (O₂^•−). Notably, the D-enantiomeric nanozyme (D-MnO₂@MM) significantly enhanced endogenous SOD2 activity via Mn²⁺ ion release, thereby suppressing the accumulation of lipid peroxides. Furthermore, based on transcriptomic and proteomic analyses, we designed an siRNA targeting the Hmox1 gene (siHmox1) and successfully loaded it onto the nanozyme platform (siHmox1@D/L-MnO₂@MM). Both in vitro and in vivo experiments confirmed that the dual mechanism, SOD2 activation and Hmox1 silencing, effectively restored mitochondrial function, attenuated ferroptosis, and significantly improved cardiac function in a rat model of chronic heart failure. Collectively, this study proposes a novel ferroptosis-targeted therapeutic strategy based on a biomimetic chiral nanozyme, offering new insights and promising therapeutic potential for the treatment of DOX-induced cardiotoxicity.

多柔比星（DOX）治疗可导致心肌细胞内铁超载，引发活性氧（ROS）的过量产生，并导致心脏毒性。超氧化物歧化酶（SOD）能有效清除活性氧，其催化活性取决于其活性位点上金属离子的结合。因此，增强金属依赖性SOD的活性是抑制心肌细胞铁下沉和减轻dox诱导的慢性心力衰竭的一种有希望的策略。在这项研究中，我们构建了一种与巨噬细胞和血小板膜共修饰的仿生手性MnO2纳米酶（D/L-MnO2@MM），可以精确靶向dox损伤的心肌组织。该纳米酶表现出类似过氧化氢酶和类似sod的活性，能有效去除过量的过氧化氢（H2O2）和超氧阴离子（O2•−）。值得注意的是，d -对映体纳米酶（D-MnO2@MM）通过Mn2+离子释放显著增强内源性SOD2活性，从而抑制脂质过氧化物的积累。此外，基于转录组学和蛋白质组学分析，我们设计了一个靶向Hmox1基因的siRNA (siHmox1)，并成功地将其加载到纳米酶平台（siHmox1@D/L-MnO2@MM）上。体外和体内实验均证实了SOD2激活和Hmox1沉默的双重机制，在慢性心力衰竭大鼠模型中有效恢复线粒体功能，减轻铁下沉，显著改善心功能。总之，本研究提出了一种基于仿生手性纳米酶的新的针对铁中毒的治疗策略，为治疗dox诱导的心脏毒性提供了新的见解和有希望的治疗潜力。

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引用次数: 0

Fishnet-like 2D magnetic nanozyme probe enables ultrasensitive bedside immunodiagnosis of bone infection pathogens 鱼网状二维磁性纳米酶探针使骨感染病原体的超灵敏床边免疫诊断成为可能

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-09 DOI: 10.1016/j.bioactmat.2025.11.043

Chongwen Wang , Changyue Xu , Jiaxuan Li , Ting Wu , Kaijie Guo , Bingjie Wang , Junyan Ai , Limin Ma , Bing Gu , Yuanchen Ma

Rapid, early, and accurate bedside diagnosis of bone infections is an urgent clinical need that remains unmet. Here, we present a fishnet-like two-dimensional magnetic nanozyme (FGDAI) that integrates three functional modules: a monolayer graphene oxide substrate providing a large reaction interface; an Fe₃O₄ interlayer conferring efficient magnetic enrichment; and two dense layers of Au@Ir nanoparticles furnishing abundant catalytic sites that act synergistically with the Fe₃O₄ to enable catalytic enhancement. This architecture delivers multiple signal amplification—“large reaction interface, magnetic enrichment, synergistic enhancement”—within an immunochromatographic assay (ICA), effectively overcoming the sensitivity and robustness limitations of traditional colorimetric ICAs when challenged by complex clinical matrices. In addition, wheat germ agglutinin (WGA) was immobilized on the 2D FGDAI surface via lyophilization as a universal peptidoglycan recognition molecule, enabling efficient, broad-spectrum bacterial binding and thereby mediating ultrasensitive, simultaneous ICA detection of two important bone-infection pathogens (Staphylococcus aureus and Pseudomonas aeruginosa). FGDAI-WGA-ICA completes testing in under 25 min with a visual limit of detection of 10 cells/mL, exhibiting high sensitivity and specificity for the target pathogens. Moreover, validation in a cohort of 83 synovial fluid samples showed high concordance with clinical reference methods, supporting its potential for real-time, bedside diagnosis of bone infections.

快速，早期，准确的床边诊断骨感染是一个迫切的临床需要，仍然没有得到满足。在这里，我们提出了一种鱼网状的二维磁性纳米酶（FGDAI），它集成了三个功能模块：单层氧化石墨烯衬底提供了一个大的反应界面；Fe3O4中间层具有高效的磁富集作用；两层致密的Au@Ir纳米颗粒提供丰富的催化位点，与Fe3O4协同作用，实现催化增强。这种结构在免疫层析分析（ICA）中提供多重信号放大-“大反应界面，磁富集，协同增强”，有效克服了传统比色法ICA在复杂临床基质挑战时的灵敏度和鲁棒性限制。此外，通过冻干将小麦胚芽凝集素（WGA）作为一种通用肽聚糖识别分子固定在二维FGDAI表面，实现了高效、广谱的细菌结合，从而介导了两种重要的骨感染病原体（金黄色葡萄球菌和铜绿假单胞菌）的超灵敏、同时的ICA检测。FGDAI-WGA-ICA在25分钟内完成检测，视觉检测限为10个细胞/mL，对目标病原体具有很高的灵敏度和特异性。此外，83个滑液样本的队列验证显示与临床参考方法高度一致，支持其用于骨感染的实时床边诊断的潜力。

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引用次数: 0

Corrigendum to “Skin-inspired phototherapeutic cryogel ameliorates infected wound healing by orchestrating mechanotransduction and immunomodulation” [Bioact. Mater. 57 (2026) 768–790] “皮肤启发的光疗低温凝胶通过协调机械传导和免疫调节改善感染伤口愈合”的更正[Bioact]。[57 (2026) 768-790]

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-08 DOI: 10.1016/j.bioactmat.2025.12.003

Sayan Deb Dutta , Jeong Man An , Md Moniruzzaman , Rumi Acharya , Youjin Seol , Hojin Kim , Aayushi Randhawa , Jong-Sung Kim , Yong-kyu Lee , Ki-Taek Lim

引用次数: 0

Ascorbate elastomer-coated ePTFE grafts inhibit neointimal hyperplasia and enhance vascular healing 抗坏血酸弹性体涂层ePTFE移植物抑制内膜增生，促进血管愈合

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-08 DOI: 10.1016/j.bioactmat.2025.10.014

Lu Yu , Emily R. Newton , David C. Gillis , Brian C. Cooley , Kui Sun , Brooke R. Dandurand , Robin Siletzky , Nick D. Tsihlis , Melina R. Kibbe

Severe peripheral arterial disease (PAD) is often treated with surgical bypass grafting using autologous vein. When veins are unavailable, small-diameter expanded polytetrafluoroethylene (ePTFE) grafts are used but are associated with long-term poor performance. To address this, we developed poly(1,8-octanediol-co-citrate-co-ascorbate) (POCA) elastomer coatings for small-diameter ePTFE grafts that indirectly release nitric oxide via decomposition of circulating S-nitrosothiols (RSNO). Graft in vivo efficacy was assessed using a guinea pig aortic interposition model to evaluate neointimal formation. After 4 weeks, POCA-Grafts demonstrated significantly less occlusion compared to uncoated ePTFE grafts (16.8 % versus 29.7 %, p < 0.0005) and POC (poly(1,8-octanediol-co-citrate))-Grafts without ascorbate (16.8 % versus 19.9 %, p < 0.005). POCA-Grafts showed a 1.6-fold increase in endothelial cell coverage and significantly reduced leukocyte and macrophage infiltration compared to uncoated ePTFE grafts, particularly in female animals. These results suggest that the POCA coating enhances graft biocompatibility by promoting endothelialization and reducing inflammation, thereby inhibiting neointimal hyperplasia and improving graft patency. Overall, these results highlight the therapeutic potential of an ascorbate-functionalized poly(diol-co-citrate) elastomer for vascular applications and support future evaluation in large animal models.

严重外周动脉疾病（PAD）通常采用自体静脉旁路移植术治疗。当静脉不可用时，使用小直径膨胀聚四氟乙烯（ePTFE）移植物，但长期表现不佳。为了解决这个问题，我们开发了用于小直径ePTFE接枝的聚（1,8-辛烷二醇-共柠檬酸盐-共抗坏血酸盐）（POCA）弹性体涂层，通过分解循环s -亚硝基硫醇（RSNO）间接释放一氧化氮。采用豚鼠主动脉间置模型评估移植的体内疗效，以评估新内膜的形成。4周后，与未包被ePTFE移植物（16.8% vs 29.7%, p < 0.0005）和不含抗坏血酸的POC（聚1,8-辛烷二醇-共柠檬酸酯）移植物（16.8% vs 19.9%, p < 0.005）相比，poca移植物的闭塞程度显著降低。与未包被ePTFE移植物相比，poca移植物内皮细胞覆盖率增加1.6倍，白细胞和巨噬细胞浸润显著减少，尤其是在雌性动物中。这些结果表明，POCA涂层通过促进内皮化和减少炎症来增强移植物的生物相容性，从而抑制内膜增生，改善移植物的通畅性。总之，这些结果突出了抗坏血酸功能化聚（二醇-共柠檬酸）弹性体在血管应用方面的治疗潜力，并支持未来在大型动物模型中的评估。

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引用次数: 0

Engineering macromolecular crowding-driven amyloid-mineral hybrid scaffolds for enhanced bone regeneration 工程大分子群体驱动淀粉样蛋白-矿物混合支架增强骨再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-08 DOI: 10.1016/j.bioactmat.2025.11.045

Yangyang Ye , Xuewen Li , He Feng , Shan Zhang , Xinye Zhou , Min Li , Fan Li , Cheng Zhi , Zeyuan Chen , Xiangyu Zhang , Zhongze Fang , Fuchun Fang , Peng Yang , Xu Zhang

The extracellular matrix (ECM) of native bone features a densely crowded, hierarchically organized architecture composed of collagen fibrils and hydroxyapatite (HAp) nanocrystals, which together confer mechanical strength and biological functionality. However, faithfully replicating this complex organic–inorganic interface in synthetic scaffolds remains a significant challenge. Here, we report a macromolecular crowding (MMC)-driven strategy to construct ECM-mimetic scaffolds using phase-transited lysozyme (PTL) as an amyloid-based protein matrix. By employing a reverse dialysis process to mimic the crowded microenvironment, amyloid proteins undergo aggregation, conformational rearrangement, and a liquid-crystalline-like phase transition, accompanied by reconstruction of the organic–inorganic interface and energetic reorganization, thereby promoting biomineralization. The resulting amyloid–mineral hybrid scaffold exhibits excellent structural stability, mechanical robustness, and bioactivity, supporting bone regeneration comparable to mineralized collagen in vitro and in vivo. Collectively, this study demonstrates that, unlike conventional water-rich and dilute scaffolds, the MMC-driven strategy provides a more biomimetic and functionally versatile platform, highlighting the feasibility of using structurally stable amyloid proteins as substitutes for collagen and offering a powerful design paradigm for next-generation bone tissue engineering scaffolds.

天然骨的细胞外基质（ECM）具有密集的、分层组织的结构，由胶原原纤维和羟基磷灰石（HAp）纳米晶体组成，它们共同赋予机械强度和生物功能。然而，在合成支架中忠实地复制这种复杂的有机-无机界面仍然是一个重大挑战。在这里，我们报告了一种大分子拥挤（MMC）驱动的策略，以相转移溶菌酶（PTL）作为淀粉样蛋白基质构建ecm模拟支架。通过采用反透析过程模拟拥挤的微环境，淀粉样蛋白经历聚集、构象重排和液晶样相变，伴随着有机-无机界面的重建和能量重组，从而促进生物矿化。由此产生的淀粉样蛋白-矿物质混合支架具有优异的结构稳定性、机械稳健性和生物活性，在体外和体内支持骨再生可与矿化胶原媲美。总的来说，本研究表明，与传统的富含水和稀释的支架不同，mmc驱动的策略提供了一个更仿生和功能更多功能的平台，突出了使用结构稳定的淀粉样蛋白作为胶原蛋白替代品的可行性，并为下一代骨组织工程支架提供了强大的设计范例。

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引用次数: 0

An intelligent nanoliposome alleviates disc degeneration and discogenic pain by inhibiting neurovascular ingrowth via a “Soil-conditioning, seed-modulating, and weeds-suppressing” strategy 一种智能纳米脂质体通过“土壤调节、种子调节和杂草抑制”策略抑制神经血管向内生长，减轻椎间盘退变和椎间盘源性疼痛

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-05 DOI: 10.1016/j.bioactmat.2025.11.048

Fudong Li , Yangyang Shi , Junxia Liu , Yangzi Yang , Chen Yan , Xiaofei Sun , Zhiqiu Zhang , Bin Zhang , Qi Wang , Mu Du , Ziran Wang , Jingchuan Sun , Ximing Xu , Kaiqiang Sun , Jiuyi Sun , Yuan Wang , Jiangang Shi

Intervertebral disc degeneration (IVDD), a primary cause of debilitating low back pain, is driven by a vicious cycle involving a harsh microenvironment (“soil”) and dysfunctional nucleus pulposus cells (“seeds”), which together promote pathological neurovascular ingrowth (“weeds”) and pain. A therapeutic strategy that can simultaneously “condition the soil” and “modulate the seed” is therefore paramount. Thus, we engineered a biomimetic intelligent nanoliposome (NM-LP^TK/RSV-MnCDs) for this dual purpose. The platform is camouflaged with NPC membranes for precise “seed”-homing and incorporates a reactive oxygen species (ROS)-responsive linker for on-demand drug release within the degenerative “soil.” It co-delivers carbonized Mn-containing nanodots (MnCDs) to “condition the soil” by scavenging ROS, and resveratrol (RSV) to “modulate the seed” by suppressing pro-neurovascular signaling. The nanoplatform demonstrated outstanding efficacy in vitro and in two distinct murine IVDD models. It effectively scavenged ROS, inhibited axonal and vascular growth, and preserved matrix synthesis. In vivo, it significantly attenuated disc degeneration, suppressed pathological neurovascular ingrowth, and alleviated pain-related behaviors. Mechanistically, we found this synergistic “soil-conditioning” and “seed-modulating” effect was mediated through the inactivation of the Hippo-YAP signaling pathway, which restored redox homeostasis and blocked aberrant remodeling. This study establishes a targeted, intelligent nanoplatform that synergistically alleviates IVDD and discogenic pain by restoring the disc ecosystem via Hippo pathway inhibition, presenting a precise therapeutic paradigm for degenerative disc disease and its associated neuropathic pain.

椎间盘退变（IVDD）是导致腰痛的主要原因，它是由一个恶性循环驱动的，涉及恶劣的微环境（“土壤”）和功能失调的髓核细胞（“种子”），它们共同促进病理性神经血管向内生长（“杂草”）和疼痛。因此，能够同时“调理土壤”和“调节种子”的治疗策略是至关重要的。因此，我们设计了一种仿生智能纳米脂质体（NM-LPTK/RSV-MnCDs）来实现这一双重目的。该平台由NPC膜伪装，用于精确的“种子”定位，并结合活性氧（ROS）响应连接物，用于在退化的“土壤”中按需释放药物。它共同递送碳化含锰纳米点（MnCDs），通过清除活性氧来“调节土壤”，同时递送白藜芦醇（RSV），通过抑制促神经血管信号来“调节种子”。该纳米平台在体外和两种不同的小鼠IVDD模型中表现出出色的功效。它能有效清除活性氧，抑制轴突和血管生长，保存基质合成。在体内，它能显著减轻椎间盘退变，抑制病理性神经血管长入，减轻疼痛相关行为。在机制上，我们发现这种协同的“土壤调节”和“种子调节”效应是通过Hippo-YAP信号通路失活介导的，该信号通路恢复氧化还原稳态并阻断异常重塑。本研究建立了一个有针对性的智能纳米平台，通过Hippo通路抑制恢复椎间盘生态系统，协同缓解IVDD和椎间盘源性疼痛，为退行性椎间盘疾病及其相关神经性疼痛提供了精确的治疗范例。

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引用次数: 0

Fibrin scaffolds for angiogenesis in soft tissue models: a systematic review 纤维蛋白支架用于软组织血管生成模型：系统综述

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-04 DOI: 10.1016/j.bioactmat.2025.10.019

Carla Verónica Fuenteslópez , Simge Bahcevanci , Viorica Patrulea , Hua Ye

Background

Fibrin is a biocompatible, angiogenic biomaterial widely used in soft tissue engineering, with outcomes influenced by scaffold formulation and design.

Aim

This systematic review evaluates how fibrin scaffold composition and design affect angiogenesis in in vitro and in vivo soft tissue models.

Methods

PubMed, Scopus, and OVID were searched on 28/Oct/2024. A two‐step screening process by three independent researchers identified original studies on fibrin scaffolds assessing endothelial formation and/or migration. Studies without experimental data or focused solely on grafts were excluded. Data on scaffold composition, manufactured objects, cell‐embedding strategies, angiogenic outcomes, and a subset of muscle‐specific studies were narratively synthesised. Risk of bias (RoB) and study quality were assessed using SYRCLE's RoB tool and a modified CAMARADES checklist.

Results & discussion

The 81 studies highlight the impact of scaffold composition on angiogenic outcomes, with human‐derived fibrinogen and pre‐embedding cells consistently supporting successful outcomes. While tube and network formation outcomes typically aligned, endothelial migration exhibited different patterns. Thrombin often contributed positively, but crosslinker effects were less clear. Muscle‐focused studies mainly used hydrogels and often included non‐endothelial cells.

Conclusions

Fibrin scaffolds are highly relevant for soft tissue engineering, with outcomes influenced by formulation, fibrinogen source, and cell embedding. However, experimental design variability and lack of standardised reporting hinder reproducibility and clinical translation. To support future research, a minimum information checklist was created to promote consistent reporting, while aggregated success rates across design parameters could guide scaffold design.

Registration & funding

PROSPERO [CRD42025612994] and OSF [10.17605/osf.io/nvfdj]. No funding body was directly involved.

纤维蛋白是一种生物相容性的血管生成生物材料，广泛应用于软组织工程，其结果受支架配方和设计的影响。目的系统评价纤维蛋白支架的组成和设计对体外和体内软组织模型血管生成的影响。方法于2024年10月28日检索spubmed、Scopus和OVID。由三位独立研究人员进行的两步筛选过程确定了纤维蛋白支架评估内皮形成和/或迁移的原始研究。没有实验数据或仅关注移植物的研究被排除在外。本文叙述地综合了有关支架组成、人造物体、细胞包埋策略、血管生成结果和肌肉特异性研究子集的数据。使用sycle的RoB工具和改良的CAMARADES检查表评估偏倚风险（RoB）和研究质量。这81项研究强调了支架成分对血管生成结果的影响，人类来源的纤维蛋白原和预嵌入细胞一致支持成功的结果。虽然管和网络的形成结果通常是一致的，但内皮细胞的迁移表现出不同的模式。凝血酶通常起到积极作用，但交联剂的作用不太明显。以肌肉为中心的研究主要使用水凝胶，通常包括非内皮细胞。结论纤维蛋白支架在软组织工程中具有重要的应用价值，其应用效果受其配方、纤维蛋白原来源和细胞包埋的影响。然而，实验设计的可变性和缺乏标准化报告阻碍了可重复性和临床翻译。为了支持未来的研究，创建了一个最小信息清单，以促进一致的报告，而跨设计参数的汇总成功率可以指导支架设计。注册&资助普洛斯普洛斯[CRD42025612994]和OSF [10.17605/ OSF .io/nvfdj]。没有供资机构直接参与。

{"title":"Fibrin scaffolds for angiogenesis in soft tissue models: a systematic review","authors":"Carla Verónica Fuenteslópez , Simge Bahcevanci , Viorica Patrulea , Hua Ye","doi":"10.1016/j.bioactmat.2025.10.019","DOIUrl":"10.1016/j.bioactmat.2025.10.019","url":null,"abstract":"<div><h3>Background</h3><div>Fibrin is a biocompatible, angiogenic biomaterial widely used in soft tissue engineering, with outcomes influenced by scaffold formulation and design.</div></div><div><h3>Aim</h3><div>This systematic review evaluates how fibrin scaffold composition and design affect angiogenesis in <em>in vitro</em> and <em>in vivo</em> soft tissue models.</div></div><div><h3>Methods</h3><div>PubMed, Scopus, and OVID were searched on 28/Oct/2024. A two‐step screening process by three independent researchers identified original studies on fibrin scaffolds assessing endothelial formation and/or migration. Studies without experimental data or focused solely on grafts were excluded. Data on scaffold composition, manufactured objects, cell‐embedding strategies, angiogenic outcomes, and a subset of muscle‐specific studies were narratively synthesised. Risk of bias (RoB) and study quality were assessed using SYRCLE's RoB tool and a modified CAMARADES checklist.</div></div><div><h3>Results & discussion</h3><div>The 81 studies highlight the impact of scaffold composition on angiogenic outcomes, with human‐derived fibrinogen and pre‐embedding cells consistently supporting successful outcomes. While tube and network formation outcomes typically aligned, endothelial migration exhibited different patterns. Thrombin often contributed positively, but crosslinker effects were less clear. Muscle‐focused studies mainly used hydrogels and often included non‐endothelial cells.</div></div><div><h3>Conclusions</h3><div>Fibrin scaffolds are highly relevant for soft tissue engineering, with outcomes influenced by formulation, fibrinogen source, and cell embedding. However, experimental design variability and lack of standardised reporting hinder reproducibility and clinical translation. To support future research, a minimum information checklist was created to promote consistent reporting, while aggregated success rates across design parameters could guide scaffold design.</div></div><div><h3>Registration & funding</h3><div>PROSPERO [CRD42025612994] and <span>OSF</span> [10.17605/osf.io/nvfdj]. No funding body was directly involved.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"56 ","pages":"Pages 703-725"},"PeriodicalIF":18.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690319","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}

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