Biomaterials最新文献_第6页

Cardiac and skeletal muscle delivery of biotherapeutics with a blood vessel epicardial substance-targeting peptide 血管心外膜物质靶向肽的心脏和骨骼肌生物治疗药物递送

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-04 DOI: 10.1016/j.biomaterials.2026.123986

Biaobiao Wang , Jiahui Cao , Jingqiao Wu , Yiwen Zhao , Yao Zhang , Frank Abendroth , Caorui Lin , Li Zhong , Huanan Yu , Yiqi Seow , Meitong Ou , Olalla Vázquez , Lin Mei , HaiFang Yin , Gang Han

Although peptide-based delivery strategies show promise for muscle and heart diseases, delivery of biotherapeutics to both skeletal and cardiac muscles remains challenging. Here, we identified a muscle-homing peptide (BV2) against blood vessel epicardial substance (BVES) by phage display. BV2 shows high binding affinity to BVES and is internalized primarily via caveolae-mediated endocytosis. Importantly, BV2 enables efficient delivery of Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomer (PMO), mCherry protein and exosomes to skeletal muscle and heart in vivo. BV2-mCherry protein and BV2-E31R anti-myostatin peptide were effectively delivered to muscle layers when microneedles loaded with these biotherapeutics were implanted on hindlimbs of mice. Muscle mass and myofiber size also significantly increased in muscle atrophy mice grafted with BV2-E31R microneedles. Moreover, significantly enhanced restoration of dystrophin protein was achieved in peripheral and cardiac muscles of dystrophin-deficient mdx and dystrophin/utrophin double-knockout mice when exosomes simultaneously modified with BV2 and PMO. These findings highlight the potency of BV2 in directing targeted delivery of diverse biotherapeutics to muscle and heart, thus providing an effective tool for DMD and other muscular and cardiac disorders.

尽管基于肽的给药策略对肌肉和心脏疾病显示出希望，但将生物治疗药物同时递送到骨骼肌和心肌仍然具有挑战性。在这里，我们通过噬菌体展示鉴定了一种针对血管心外膜物质（BVES）的肌肉归巢肽（BV2）。BV2对BVES具有很高的结合亲和力，主要通过小泡介导的内吞作用被内化。重要的是，BV2能够在体内将杜氏肌营养不良症（DMD）磷酸二酯morpholino oligomer （PMO）、mCherry蛋白和外泌体有效地递送到骨骼肌和心脏。在小鼠后肢植入装有BV2-mCherry蛋白和BV2-E31R抗肌肉生长抑制素肽的微针，可以有效地将这些生物治疗药物传递到肌肉层。移植BV2-E31R微针后，肌肉萎缩小鼠的肌肉质量和肌纤维大小也显著增加。此外，当外泌体同时被BV2和PMO修饰时，肌营养不良蛋白缺陷mdx和肌营养不良蛋白/肌营养不良蛋白双敲除小鼠外周肌和心肌中肌营养不良蛋白的恢复显著增强。这些发现强调了BV2在指导多种生物治疗药物靶向递送肌肉和心脏方面的效力，从而为DMD和其他肌肉和心脏疾病提供了有效的工具。

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引用次数: 0

Wireless magnetoelectric hydrogel spray reprograms the CXCL12-autophagy axis for spatiotemporally controlled cervical nerve root regeneration 无线磁电水凝胶喷雾重新编程cxcl12自噬轴，实现时空可控的颈神经根再生。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123983

Rongguo Yu , Jiamei Xiao , Zhencheng Xiong , Xiaoyang Wu , Chaoyi Zhang , Yusheng Zhang , Kangkang Huang , Jing Sun , Hongsong Fan , Hao Liu

Cervical nerve root injury (CNRI) presents significant clinical challenges owing to complex anatomical constraints and poor intrinsic regenerative capacity. In this study, we introduce an in situ-sprayable magnetoelectric hydrogel (DG/FBD) engineered through dynamic covalent assembly and photo-triggered stabilization. The construction of critical boronate ester bonding between dopamine-modified Fe₃O₄@BaTiO₃ nanoparticles and phenylboronic acid-functionalized dextran endows DG/FBD with optimal viscosity (87 mPa s), rapid gelation (<2s) and robust tissue adhesion (22.11 kPa), allowing for precise deposition along tortuous nerve roots while conforming to branched cervical anatomy. We then establish a wireless magnetic actuation platform with conductivity modulation enabled spatiotemporally controllable bioelectronic interfacing. In CNRI models loading with magnetic stimulation, we found the hydrogel spray significantly promotes axonal regeneration and myelination, and importantly, improving functional recovery, including enhanced pain and temperature sensation, as well as increased grip strength. We also demonstrate accelerated neural differentiation of BMSCs and attenuated astrogliosis by in vitro studies. Mechanistically, we reveal that magnetoelectrically triggered CXCL12 upregulation drives Schwann cells remodeling through PI3K/AKT/mTOR inhibition and enhances autophagic flux, establishing a bioelectronic-metabolic bridge where the CXCL12-autophagy axis emerges as a fundamental regulatory node for neural regeneration. Collectively, our work pioneers wireless magnetoelectric regulation of chemokine-directed neural repair via an integrated sprayable hydrogel system that overcomes cervical interfacing constraints, establishing a promising platform for spatiotemporal microenvironmental reprogramming in complex neuropathies.

颈神经根损伤（CNRI）由于其复杂的解剖限制和较差的内在再生能力，给临床带来了重大挑战。在这项研究中，我们介绍了一种通过动态共价组装和光触发稳定化设计的可现场喷涂的磁电水凝胶（DG/FBD）。在多巴胺修饰的Fe3O4@BaTiO3纳米颗粒和苯硼酸功能化的葡聚糖之间建立了临界硼酸酯键，使DG/FBD具有最佳粘度（87 mPa s）、快速凝胶化(

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引用次数: 0

Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy 葛根碳点调节肠道菌群和代谢物，协同治疗糖尿病中泛器官靶向巨噬细胞极化。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123967

Jianing Yi , Yuanyu Tang , Yilin Chen , Liang Chen , Dongxue Geng , Luyao Liu , Jie Yu , Lianhong Zou , Jie Zeng , Minhuan Lan , Wenjie Gao , Ming Gao

Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root–derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota–metabolite–macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.

2型糖尿病是一种以代谢功能障碍和慢性炎症为特征的全身性疾病，但针对这两方面的策略仍然有限。在这里，我们提出了葛根衍生的碳点（KRCDs）作为一种天然纳米材料，可以重新编程肠道微生物群-代谢物-免疫轴，以恢复系统稳态。KRCDs具有纳米级结晶度、丰富的O/N官能团和较强的抗氧化活性。在高脂肪饮食/链脲佐菌素诱导的糖尿病小鼠中，KRCDs显著降低了空腹血糖，改善了葡萄糖耐量和胰岛素敏感性，纠正了脂质谱，减少了肝脏脂肪变性，而没有可检测到的毒性。多组学分析显示，微生物多样性增加，厌氧菌等有益菌丰富，粪便代谢物重塑，吲哚-3-甲醛（I3A）显著增加。流式细胞术和免疫荧光证实，这种代谢物与脂肪组织、肠道、肾脏、肝脏和胰腺中m2样巨噬细胞极化增强相关。来自krcd治疗供体的粪便微生物群移植重现了代谢改善和全器官M2极化，证实了微生物群依赖的机制。通过建立肠道微生物-代谢物-巨噬细胞极化通路，KRCDs作为安全的植物纳米平台，同时纠正代谢和免疫失衡，为糖尿病的多靶点干预提供了一种有希望的策略。

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引用次数: 0

Protein-anchored near-infrared heptamethine cyanine photosensitizer with ultralong retention for phototherapy of large tumors 蛋白锚定的近红外超长保留七甲基氰氨酸光敏剂用于大肿瘤的光疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123914

Yunjiao Han , Maomao He , Linhao Zhang , Chaogan Liu , Yongchangk Qiao , Yinghua Li , Jiangli Fan , Wen Sun , Xiaojun Peng

Conventional photosensitizers frequently exhibit nonspecific accumulation in organs and are rapidly cleared from tumor sites, posing significant challenges to the precision and efficacy of in vivo phototherapy. This study presents a novel photosensitizer that markedly enhances tumor-specific accumulation and retention for up to 25 days, outperforming all existing photosensitizers. The photosensitizers are synthesized by incorporating two 3,5-dioxocyclohexanecarboxylic acid moieties onto the heptamethine cyanine scaffold. Notably, the photothermal conversion efficiency (58.28 %) and ROS generation of the synthesized Cy7DA are significantly enhanced in the NIR range (808 nm) compared to IR780 derivatives, through assembly-mediated intermolecular aggregation effect. The intrinsic tumor-targeted Cy7DA preferentially accumulates within the mitochondria of cancer cells, where it forms irreversible covalent interactions with overexpressed sulfonic acid proteins. This interaction resulted in ultralong tumor retention and nearly complete growth inhibition of large tumors (approximately 300 mm³) in vivo, following single-dose administration and three laser irradiation sessions. This research represents the first example of single-molecule photosensitizers for ultralong NIR fluorescence imaging of tumors, coupled with integrated photodynamic and photothermal therapy.

传统的光敏剂经常在器官中表现出非特异性积累，并迅速从肿瘤部位清除，这对体内光疗的准确性和有效性提出了重大挑战。本研究提出了一种新型光敏剂，可显著增强肿瘤特异性积累和保留长达25天，优于所有现有的光敏剂。光敏剂是通过将两个3,5-二氧环己烷羧酸基团结合到七甲基菁支架上合成的。值得注意的是，与IR780衍生物相比，合成的Cy7DA在近红外（808 nm）范围内的光热转换效率（58.28%）和ROS生成显著增强，这是通过组装介导的分子间聚集效应。固有的肿瘤靶向Cy7DA优先在癌细胞的线粒体内积累，与过表达的磺酸蛋白形成不可逆的共价相互作用。在单次给药和三次激光照射后，这种相互作用导致体内大肿瘤（约300 mm3）的超长肿瘤保留和几乎完全的生长抑制。该研究是单分子光敏剂用于肿瘤超近红外荧光成像，结合光动力和光热综合治疗的第一个例子。

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引用次数: 0

A comparative study assessing neural recording quality and inflammatory tissue response between stiff and flexible microelectrode arrays 一个比较研究评估神经记录质量和炎症组织反应之间的刚性和柔性微电极阵列。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-18 DOI: 10.1016/j.biomaterials.2025.123929

Vaishnavi Dhawan , Bingchen Wu , Sharada Narayanan , Delin Shi , Yugma Patel , Xinyan Tracy Cui

Implantable microelectrode arrays (MEAs) are powerful tools for neurophysiological studies and hold tremendous potential as a key component of clinical neuroprostheses. However, their long-term efficacy is hampered by inflammatory responses to implantation. This study examines the impact of MEA substrate rigidity on neural recording quality and inflammatory tissue responses. We implanted stiff silicon-based and flexible polyimide-based MEAs with similar geometries in the deep brain region of the mouse striatum and performed weekly impedance and electrophysiological measurements over 4 weeks. The flexible MEAs demonstrated more reliable recording quality in terms of stable signal-to-noise ratio, single-unit yield, peak-to-peak amplitude, noise, and impedance, compared to the stiff probes, whose performance deteriorated over time. Endpoint histological analyses were performed to assess the glial scarring (Iba-1, GFAP), blood-brain barrier integrity (IgG), mechanosensitive ion channel expression (Piezo1), and neuronal population (NeuN and NF200) around the implant site. We found reduced microglial activation and IgG fouling within a 50-μm radius around the flexible MEAs compared to the stiff group. Additionally, a higher expression of Piezo1 was observed localized around the stiff MEA, correlating positively with increased Iba-1 and GFAP intensity. Our results show that flexible MEAs have improved device-tissue integration, indicated by lower inflammation levels and better recording stability. This research underscores the critical role of MEA substrate rigidity in influencing adverse tissue reactions, especially for deep brain regions. This understanding will improve our ability to design stable and reliable devices for chronic neural interface devices and beyond.

植入式微电极阵列（MEAs）是神经生理学研究的有力工具，作为临床神经假体的重要组成部分具有巨大的潜力。然而，它们的长期疗效受到植入的炎症反应的阻碍。本研究探讨了MEA底物刚性对神经记录质量和炎症组织反应的影响。我们在小鼠纹状体的脑深部植入具有相似几何形状的硬硅基和柔性聚酰亚胺基mea，并在4周内每周进行阻抗和电生理测量。与刚性探头相比，柔性探头在稳定的信噪比、单产率、峰对峰幅度、噪声和阻抗方面表现出更可靠的记录质量，而刚性探头的性能会随着时间的推移而恶化。通过终点组织学分析评估植入部位周围的胶质瘢痕（Iba-1、GFAP）、血脑屏障完整性（IgG）、机械敏感离子通道表达（Piezo1）和神经元群（NeuN和NF200）。我们发现，与刚性组相比，柔性mea周围50 μm半径内的小胶质细胞活化和IgG污染减少。此外，在僵硬的MEA周围观察到较高的Piezo1表达，与Iba-1和GFAP强度的增加呈正相关。我们的研究结果表明，柔性mea改善了设备与组织的整合，表明炎症水平较低，记录稳定性更好。这项研究强调了MEA底物刚性在影响不良组织反应中的关键作用，特别是在脑深部区域。这种理解将提高我们为慢性神经接口设备及其他设备设计稳定可靠设备的能力。

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引用次数: 0

Multimodal synergistic effects and theranostic integration of hafnium-based nanoradiosensitizers for enhancing precision radiotherapy 铪基纳米放射增敏剂的多模态协同效应和治疗整合以增强精确放疗。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123918

Yiwei Chen , Zhenyu Zhou , Dengxia Wang , Chuqiao Liu , Chunxiang Mo , Suqing Tian , Ying Wu , Jibin Song

Radiotherapy remains a cornerstone in oncology, yet its efficacy is limited by tumor radioresistance and off-target toxicity. This review elucidates the transformative potential of hafnium (Hf)-based radiosensitizers in overcoming these challenges. Leveraging Hf's high atomic number, these Hf-based biomaterials enhance X-ray energy deposition through photoelectric and Auger effects, generate cytotoxic reactive oxygen species (ROS), and modulate immunosuppressive tumor microenvironments to enhance radiotherapy effect. Their distinctive capability to achieve multimodal synergy by integrating radiotherapy with photodynamic, chemotherapeutic, or immunotherapeutic strategies enables precise targeting and significantly enhances antitumor responses. Subsequently, this review rigorously assessed the current synthetic methodologies for Hf-based radiosensitizers, along with their capacities and limitations in terms of controlling material properties and ensuring scalability. Advanced imaging modalities such as fluorescence, CT, SPECT, MRI, and PA further establish Hf-based systems as theranostic platforms for real-time tumor localization and treatment monitoring. While clinical candidates like NBTXR3 exhibit promising trial outcomes, challenges remain in mechanistic clarification, biocompatibility optimization, and controlled in vivo degradation. Emerging AI-driven design and multidisciplinary integration hold promise to expedite clinical translation, advancing Hf-based radiosensitizers toward intelligent, personalized cancer therapy paradigms. This work highlights Hf's critical role in redefining precision radiotherapy and delineates a roadmap for next-generation oncological intervention.

放疗仍然是肿瘤学的基石，但其疗效受到肿瘤放射耐药和脱靶毒性的限制。这篇综述阐明了铪（Hf）基放射增敏剂在克服这些挑战方面的变革潜力。这些基于Hf的生物材料利用Hf的高原子序数，通过光电和俄歇效应增强x射线能量沉积，产生细胞毒性活性氧（ROS），调节免疫抑制肿瘤微环境，增强放疗效果。通过将放射治疗与光动力、化疗或免疫治疗策略相结合，它们具有独特的多模式协同作用能力，能够精确靶向并显著增强抗肿瘤反应。随后，本综述严格评估了目前基于hf的放射增敏剂的合成方法，以及它们在控制材料特性和确保可扩展性方面的能力和局限性。先进的成像技术如荧光、CT、SPECT、MRI和PA进一步建立了基于高频的系统作为实时肿瘤定位和治疗监测的治疗平台。虽然像NBTXR3这样的临床候选药物显示出有希望的试验结果，但在机制澄清、生物相容性优化和体内降解控制方面仍然存在挑战。新兴的人工智能驱动设计和多学科整合有望加快临床转化，将基于高频的放射增敏剂推向智能、个性化的癌症治疗范式。这项工作强调了Hf在重新定义精确放疗中的关键作用，并描绘了下一代肿瘤干预的路线图。

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引用次数: 0

A spatiotemporally programmed bilayer coating for immunomodulatory and osteogenic enhancement of artificial ligament-bone integration 一种用于人工韧带-骨整合免疫调节和成骨增强的时空程序化双层涂层

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-22 DOI: 10.1016/j.biomaterials.2025.123940

Tianwu Chen , Shuang Wang , Wei Wu , Jiawei Liu , Peng Zhang , Xiaopei Wu , Honglian Dai

Polyethylene terephthalate (PET) artificial ligaments have been widely applied in anterior cruciate ligament (ACL) reconstruction due to their excellent mechanical properties. However, their biological inertness often results in poor graft-bone integration, potentially limiting long-term clinical outcomes. Recent studies have highlighted the temporally dynamic nature of the peri-implant microenvironment following implantation, where early-stage oxidative stress, inflammatory responses, and potential bacterial contamination disrupt the transition to vascularized bone regeneration. Therefore, the development of a spatiotemporally responsive interfacial system capable of adapting to this pathological-to-regenerative shift is essential for enhancing the biological performance of synthetic grafts. Here, we propose a bilayered functional coating strategy with phase-specific responsiveness and spatial complementarity. The outer layer comprises a hyaluronic acid-based hydrogel embedded with molybdenum disulfide (MoS₂) nanosheets, enabling early-stage reactive oxygen species (ROS) scavenging and near-infrared (NIR)-activated photothermal antibacterial effects. The inner layer, composed of plasma-sprayed strontium-doped hydroxyapatite (Sr-HA), is activated under stabilized conditions to induce macrophage polarization toward the M2 phenotype and promote angiogenic osteogenesis. In a rat ACL reconstruction model, this bilayered coating significantly improved new bone formation and graft–bone integration. Collectively, this study presents a spatiotemporally programmable interfacial modulation strategy that aligns with the healing rhythm of ACL reconstruction, achieving a closed-loop regulation from early inflammation suppression to late-stage immuno-osteogenic regeneration. This approach offers a mechanistically grounded and translationally promising pathway for functionalizing synthetic ligament grafts.

聚对苯二甲酸乙二醇酯（PET）人工韧带因其优异的力学性能在前交叉韧带（ACL）重建中得到了广泛的应用。然而，它们的生物惰性往往导致移植物骨整合不良，潜在地限制了长期临床结果。最近的研究强调了植入后种植体周围微环境的时间动态性质，其中早期氧化应激、炎症反应和潜在的细菌污染破坏了向血管化骨再生的过渡。因此，开发一种能够适应这种病理到再生转变的时空响应界面系统对于提高合成移植物的生物学性能至关重要。在这里，我们提出了一种具有相位特异性响应和空间互补性的双层功能涂层策略。外层包括透明质酸基水凝胶，其中嵌入二硫化钼（MoS2）纳米片，具有早期活性氧（ROS）清除和近红外（NIR）激活的光热抗菌作用。内层由等离子喷涂的锶掺杂羟基磷灰石（Sr-HA）组成，在稳定条件下被激活，诱导巨噬细胞向M2表型极化，促进血管成骨。在大鼠ACL重建模型中，这种双层涂层显著改善了新骨的形成和移植物骨的整合。总的来说，本研究提出了一种时空可编程的接口调节策略，该策略与ACL重建的愈合节奏一致，实现了从早期炎症抑制到晚期免疫成骨再生的闭环调节。这种方法为合成韧带移植物的功能化提供了一种机制基础和翻译前景广阔的途径。

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引用次数: 0

Synergistic intercellular junction and anti-inflammation wound healing therapy via bioengineered hybrid nanovesicles 通过生物工程杂交纳米囊泡协同细胞间连接和抗炎症伤口愈合治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-10 DOI: 10.1016/j.biomaterials.2026.123999

Shi-Yi Zhang , Zhi-Ying He , Ze-Rui Zhou , Han-Bin Xu , Shi-Yu Zheng , Xin-Yue Liu , Meng-Qi Zhao , Bin-Bin Chen , Da-Wei Li , Ruo-Can Qian , Jiang-Wei Tian

Impaired skin wound healing with excessive inflammation affects millions of patients globally. The resulting chronic pain can severely impact the quality of life for people afflicted by the condition. However, the treatment of skin wounds faces enormous challenges due to complex wound microenvironments. Here, we report the design of bioengineered hybrid nanovesicles (BHNVs) that enable advanced wound healing by concurrently providing effective intercellular junction and inflammation relief. The surface of hybrid nanovesicles is modified by trans-membrane DNA functional structures with a zipper part at the outside and a DNAzyme signal output part at the inside. Asiaticoside, an active ingredient from herbal medicines, and signal recognition DNA complex are encapsulated into the nanovesicles. From both outside and inside, these components of the hybrid nanovesicles work synergistically to address wound healing from both extra- and intracellular perspectives. Upon vesicle-cell fusion, the zipper part at the outside can facilitate cell-cell junction, and the DNAzyme signal output part at the inside can hinder while monitoring inflammatory responses. The released Asiaticoside can improve cell proliferation, enhance angiogenesis, accelerate cell migration/adhesion, and promote wound healing with the combination effect of anti-oxidation and anti-ulceration. Together, BHNVs are shown to successfully accelerate wound healing and prevent inflammation. Favorable therapeutic outcomes are achieved both in vitro and in vivo, indicating a robust modality for local wound management with enhanced therapeutic effects.

皮肤伤口愈合受损并伴有过度炎症影响着全球数百万患者。由此产生的慢性疼痛会严重影响患者的生活质量。然而，由于复杂的伤口微环境，皮肤伤口的治疗面临着巨大的挑战。在这里，我们报道了生物工程杂交纳米囊泡（bhnv）的设计，它通过同时提供有效的细胞间连接和炎症缓解来实现高级伤口愈合。杂化纳米囊泡表面采用外拉链部分、内DNAzyme信号输出部分的跨膜DNA功能结构修饰。将中药活性成分积雪草苷和信号识别DNA复合物包裹在纳米囊泡中。从外部和内部来看，混合纳米囊泡的这些成分协同作用，从细胞外和细胞内的角度解决伤口愈合问题。囊泡-细胞融合时，外部的拉链部分促进细胞-细胞连接，内部的DNAzyme信号输出部分在监测炎症反应时起到阻碍作用。释放的积雪草苷具有促进细胞增殖、促进血管生成、加速细胞迁移/粘附、促进创面愈合等作用，具有抗氧化和抗溃疡的联合作用。研究表明，bhnv可以成功地加速伤口愈合和预防炎症。体外和体内均取得了良好的治疗效果，这表明局部伤口管理具有增强治疗效果的强大模式。

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引用次数: 0

Adaptive hydrogel platform for nitric oxide release and post-infarction cardiac microenvironment modulation 自适应水凝胶平台一氧化氮释放和梗死后心脏微环境调节。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123980

Yu Wu , Wen Zhang , Linlin Huang , Xinping Xu , Yue Wang , Long Bai , Li Yang , Cheng Hu , Yunbing Wang

After myocardial infarction (MI), oxidative stress, inflammatory response and myocardial fibrosis severely impair tissue regeneration. Aiming at the problem that multifunctional hydrogel systems are difficult to achieve precise therapeutic regulation due to limited response characteristics and insufficient synergistic effect. Here, we developed an adaptive hydrogel platform for targeted nitric oxide (NO) release and post-infarction cardiac microenvironment modulation. A small molecule phenylboronic acid-based cross-linker (N(BA)₄) with a four-arm topology was reported for the first time, and it was combined with Nitroso glutathione (GSNO)-modified polyvinyl alcohol (PVA) to prepare the hydrogel platform. For the multi-stage of myocardial repair, bioactive microspheres with programmed delivery function were prepared, which could rapidly release the salvianolic acid B in the pre-infarct stage to exert antioxidant and pro-angiogenic effects, and continuously release the fibrosis inhibitor Galunsertib in the post-infarct stage to inhibit fibrosis. The pathologically responsive composite hydrogel system enables precise and efficient MI therapy through a cascade-triggered drug release mechanism and multi-pathway synergy. It provides a novel and promising strategy to overcome the challenges of different pathological stages in the infarcted cardiac microenvironment.

心肌梗死（MI）后，氧化应激、炎症反应和心肌纤维化严重损害组织再生。针对多功能水凝胶系统反应特性有限、协同效应不足难以实现精准治疗调控的问题。在这里，我们开发了一种靶向一氧化氮（NO）释放和梗死后心脏微环境调节的自适应水凝胶平台。首次报道了一种具有四臂拓扑结构的小分子苯硼酸交联剂N(BA)4，并将其与亚硝基谷胱甘肽（GSNO）改性聚乙烯醇（PVA）结合制备水凝胶平台。针对多阶段心肌修复，制备具有程序化递送功能的生物活性微球，可在梗死前快速释放丹酚酸B，发挥抗氧化和促血管生成作用，在梗死后持续释放纤维化抑制剂Galunsertib，抑制纤维化。病理反应性复合水凝胶系统通过级联触发的药物释放机制和多途径协同作用，能够精确有效地治疗心肌梗死。它为克服梗死心脏微环境中不同病理阶段的挑战提供了一种新颖而有前途的策略。

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引用次数: 0

An innate immunity-reprogramming hydrogel nips postoperative adhesions in the bud via transforming pathological healing into physiological recovery 先天免疫重编程水凝胶通过将病理愈合转化为生理恢复，将术后粘连扼杀在萌芽状态

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-31 DOI: 10.1016/j.biomaterials.2025.123972

Yinqi Chen , Jiafeng Wang , Yechun Wang , Zimeng Liu , Jiajia Ying , Xuefei Zhou , Tianhua Zhou , Haiping Jiang , Xiangrui Liu , Quan Zhou

Postoperative adhesions are frequent and challenging complication lacking effective prevention. Evidence indicates that innate immune responses triggered by surgical trauma critically influence whether normal tissue repair progresses to pathological adhesions, highlighting early inflammatory responders as key intervention targets. Here, we successfully transformed natural hyaluronic acid (HA) into a potent innate inflammation modulator through a one-step sulfoxide-conjugation strategy. The resultant sulfoxide-conjugated HA (SOHA) demonstrated near-complete prevention of adhesion formation across multiple clinically relevant animal models, including those for secondary injury, long-term abdominal adhesions, and pericardial–pleural adhesions. Mechanistic investigations reveal that, unlike traditional physical barriers that primarily inhibit the late-stage adhesion of activated fibroblasts, SOHA addresses postoperative adhesions at their inception by reprogramming early innate inflammatory responses. It shifts the neutrophil cell death mode from acute, pro-inflammatory NETosis to more regulated, immunologically silent apoptotic process. Furthermore, it selectively restrains the early accumulation of large peritoneal macrophages (LPMs) in damaged tissues, redirecting them towards a reparative M2-like phenotype through the efferocytic clearance of apoptotic neutrophils, thereby promoting their timely involvement during the resolution phase of inflammation. This dual regulation of innate immunity effectively interrupts the postoperative inflammatory cascade and subsequent fibrotic progression, thus effectively shifting the pathological tissue repair into physiological healing.

术后粘连是常见且具有挑战性的并发症，缺乏有效的预防。有证据表明，手术创伤引发的先天免疫反应对正常组织修复是否发展为病理性粘连具有重要影响，因此早期炎症反应者是关键的干预目标。在这里，我们通过一步亚砜偶联策略成功地将天然透明质酸（HA）转化为一种有效的先天炎症调节剂。由此产生的亚砜偶联HA （SOHA）在多个临床相关动物模型中几乎完全预防了粘连的形成，包括继发性损伤、长期腹腔粘连和心包-胸膜粘连。机制研究表明，与传统的物理屏障主要抑制活化成纤维细胞的晚期粘连不同，SOHA通过重新编程早期先天炎症反应，在术后粘连开始时解决粘连问题。它将中性粒细胞死亡模式从急性、促炎的NETosis转变为更受调节的、免疫沉默的凋亡过程。此外，它选择性地抑制大腹膜巨噬细胞（lpm）在受损组织中的早期积累，通过对凋亡中性粒细胞的efferocytic清除，将它们定向到修复性m2样表型，从而促进它们在炎症消退阶段的及时参与。这种先天免疫的双重调控有效地阻断了术后炎症级联和随后的纤维化进展，从而有效地将病理性组织修复转变为生理性愈合。

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引用次数: 0