Biomaterials最新文献_第10页

Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models 双纳米外泌体包封水凝胶促进伤口愈合跨越异种和同种异体模型

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-27 DOI: 10.1016/j.biomaterials.2025.123953

Bibi S. Subhan , Sydney E. Hanson , Dianny Almanzar , Juan F. Cortes Troncoso , Priya Katyal , Jonathan W. Sun , Hao-Wei Shih , Tamara Mestvirishvili , Michael Meleties , Fernando Arias , Andrew Wang , Kelly Ruggles , Igor Dolgalev , Paolo Mita , Jin Kim Montclare , Piul S. Rabbani

Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel’s modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.

慢性伤口，特别是糖尿病患者，由于微血管受损和愈合延迟，构成了一个重大的临床挑战。这项研究提出了Exo-Q，一种新型的热响应性水凝胶，由工程Q蛋白纳米纤维与外泌体（一类囊泡细胞间通讯介质）共凝胶形成。Exo-Q在生理温度下从凝胶转变为粘弹性溶液，使外泌体能够在初始爆发释放后持续释放的情况下局部局部递送。在糖尿病小鼠伤口模型中，Exo-Q有效地将人骨髓多能基质细胞衍生的外泌体直接递送到伤口床，在那里它们积聚在肉芽组织的内皮细胞中，没有可检测到的全身分布。在严格和可复制的细胞培养条件下产生的外泌体始终携带富含mirna的生物大分子货物，这些mirna在血管生成相关基因中具有有效的靶标，表明它们具有治疗潜力。外用Exo-Q导致广泛的新生血管化肉芽组织，显著加速伤口愈合，达到与非糖尿病伤口相当的水平。重要的是，水凝胶的模块化设计保持了Q蛋白纳米纤维和外泌体的功能完整性，证明了与全层人体伤口的兼容性。该平台允许量身定制，以解决糖尿病伤口愈合的关键阶段，同时确保低剂量的疗效，潜在地实现患者给药治疗。通过利用先进的生物材料，Exo-Q提高了基于外泌体的糖尿病伤口干预的治疗效果，为慢性、不愈合的伤口提供了局部、非侵入性的解决方案。这种创新的水凝胶平台代表了一种模块化治疗策略，在再生医学的临床应用中具有重要的潜力。

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引用次数: 0

Engineered Needlepatch for the treatment of acute kidney injury 工程针贴治疗急性肾损伤

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-26 DOI: 10.1016/j.biomaterials.2025.123936

Xingli Zhao , Xiaochen Li , Lang He , Xin Gong , Yanhong Wang , Lin Chen , Hao Tian , Yeqin Wang , Xinrong Xu , Tai Sheng , Min Liu , Junxuan Li , Di Liu , Lang Li , Wenyan Zhao , Wen Zeng

In acute kidney injury (AKI), the loss of peritubular capillaries further aggravates the disease. Cell transplantation represents an innovative precision therapeutic strategy. However, the low survival rate of transplanted cells and the low therapeutic efficiency remain challenges for clinical application. Here, we constructed a Needlepatch loaded with the nanozymes GTFG@Fe₃O₄, and attached to a 3D printed patterned cell tubular networks hydrogel patch for in situ kidney transplantation. In the early stage of AKI, the nanozymes can effectively target ATG4B protein-enriched microenvironment, preventing the infiltration of the NLRP3 inflammasome and cellular damage, relieving inflammation. During the later stage, human induced pluripotent stem cells (hiPSCs) derived podocyte-attached patterned tubular networks of endothelial cells facilitated the rebuilding of renal microvascular network, promoting regeneration. In this process, the integration of the Needlepatch with host kidney is established. This engineered kidney composite patch alleviates the damage caused by AKI in a programmed manner and demonstrates considerable therapeutic potential in promoting renal microvascular reconstruction.

在急性肾损伤（AKI）中，小管周围毛细血管的丧失进一步加重了疾病。细胞移植是一种创新的精准治疗策略。然而，移植细胞的存活率低，治疗效果低，仍然是临床应用的挑战。在这里，我们构建了一个加载纳米酶GTFG@Fe3O4的Needlepatch，并连接到3D打印的细胞管状网络水凝胶贴片上，用于原位肾移植。在AKI早期，纳米酶能有效靶向ATG4B蛋白富集的微环境，阻止NLRP3炎性体的浸润和细胞损伤，缓解炎症反应。在后期，人诱导多能干细胞（hipsc）衍生的足细胞附着的内皮细胞管状网络促进了肾微血管网络的重建，促进了再生。在此过程中，针贴与宿主肾脏的整合得以建立。这种工程肾脏复合贴片以程序化的方式减轻了AKI引起的损伤，在促进肾脏微血管重建方面显示出相当大的治疗潜力。

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引用次数: 0

Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers 工程生物活性纤维结构：具有短胶原微纤维的生物打印满载干细胞的胶原衍生水凝胶。

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.2025.123965

Hongjuan Weng , Monize C. Decarli , Wen Chen , Katrien V. Bernaerts , Lorenzo Moroni

Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by in situ stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.

天然水凝胶（如胶原蛋白水凝胶）在理解细胞-基质相互作用方面具有良好的潜力，并在组织工程中得到应用。然而，具有良好的可打印性、形状保持性和稳定性的生物打印细胞负载天然水凝胶仍然是一个挑战。本研究将非水溶性短型胶原I型微纤维（COL-I μFiber）与水溶性甲基丙烯酸化胶原肽（COPMA）和黄原胶（XG）共混，形成互渗透网络，并生物打印成稳定的天然来源的COPMA-μFiber-XG结构，随后进行原位干细胞增殖和分化。首先，为了提高COPMA的打印性能和力学性能，研制了一种具有快速紫外固化和自愈性能的COPMA-μFiber-XG生物墨水。包被的人间充质干细胞（hMSCs）在生物打印构建体中沿col - 1 μ纤维扩散，28天内代谢活性增加，细胞外基质和生物活性蛋白（col - 1和sclcleraxis）的产生增加。col - 1 μFibers和纤维状COPMA基质提供的内部生物物理生化信号与外源生化信号（如转化生长因子- β 3）协同作用，进一步促进干细胞分化。总体而言，生物打印纤维COPMA-μFiber-XG构建物具有生物相容性和生物活性，可支持hMSCs的增殖和分化。

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引用次数: 0

Alkalinity and LSPR effect-based cuproptosis sensitizer to reverse tumor microenvironment for melanoma therapy 碱度和LSPR效应为基础的铜增生增敏剂逆转肿瘤微环境用于黑色素瘤治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-13 DOI: 10.1016/j.biomaterials.2025.123913

Lidan Liu , Mei Li , Panpan Huo , Shun Xing , Feng Peng , Haifeng Zhang , Haobo Pan , Yuehua Li , Xuanyong Liu

Cuproptosis is a promising therapeutic strategy for tumor, but its therapeutic efficacy is limited by the weak acidity and high concentration of glutathione (GSH) in the tumor microenvironment (TME). In this study, a novel alkalinity and localized surface plasmon resonance (LSPR) effect-based nanoreactor (MgO/Cu@C) is constructed to sensitise cuproptosis. Firstly, the alkalinity produced by MgO could reverse the acidic tumor microenvironment. Additionally, near-infrared (NIR) induced photothermal property and LSPR effect synergistic alkalinity can enhance GSH depletion of MgO/Cu@C. Thus, MgO/Cu@C+NIR sensitizes melanoma cells to cuproptosis by reversing TME. Furthermore, RNA sequencing transcriptome analysis confirms that MgO/Cu@C+NIR induces cuproptosis through copper overload-triggered lipoylated protein aggregation, inhibition of tumor metabolic pathways by alkalinity, NIR-drived HSP hyperactivation that depletes ATP reserves, and phosphatidylinositol signaling-mediated hijacking of survival pathways, which synergistically enforces irreversible metabolic collapse for melanoma cells. Meanwhile, MgO/Cu@C+NIR could inhibit bacterial infection and promote wound healing, thus addressing dual clinical applications for melanoma treatment and wound healing. Particularly, this study firstly reveals the mechanisms by which alkalinity and LSPR effect potentiate GSH depletion, as well as that alkalinity could sensitise cuproptosis by reversing the acidic microenvironment of tumor. The study provides a promising perspective for potential melanoma treatment based on cuproptosis.

cuprotosis是一种很有前景的肿瘤治疗策略，但其治疗效果受到肿瘤微环境（TME）中弱酸性和高浓度谷胱甘肽（GSH）的限制。在本研究中，构建了一种基于碱度和局部表面等离子体共振（LSPR）效应的纳米反应器（MgO/Cu@C）来敏化铜还原。首先，MgO产生的碱性可以逆转肿瘤的酸性微环境。此外，近红外（NIR）诱导的光热性质和LSPR效应协同碱度可以增强GSH的消耗MgO/Cu@C。因此，MgO/Cu@C+NIR通过逆转TME使黑色素瘤细胞对铜突变敏感。此外，RNA测序转录组分析证实，MgO/Cu@C+NIR通过铜超载触发的脂酰化蛋白聚集、碱度抑制肿瘤代谢途径、NIR驱动的HSP过度激活（耗尽ATP储备）以及磷脂酰肌醇信号介导的生存途径劫持（协同执行黑色素瘤细胞不可逆转的代谢崩溃）诱导铜增生。同时，MgO/Cu@C+NIR可抑制细菌感染，促进创面愈合，从而解决了黑色素瘤治疗和创面愈合的双重临床应用。特别是，本研究首次揭示了碱度和LSPR效应增强GSH耗竭的机制，以及碱度通过逆转肿瘤酸性微环境致铜增生的机制。该研究为基于铜突起的潜在黑色素瘤治疗提供了一个有希望的前景。

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引用次数: 0

Biomimetic antimicrobial peptides against gram-positive bacteria 抗革兰氏阳性细菌的仿生抗菌肽

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.2025.123916

Yu-Ting Li , Tian-Ci Wei , Jun-Xiao Yuan , Jia-Qi Feng , Pei-Pei Yang , Shu-Sheng Tang , Lei Wang , Hao Wang

Anti-Gram-positive bacteria, including multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), face significant challenges due to their robust cell wall structures, biofilm formation, and resistance mechanisms. Natural antimicrobial peptides (NAMPs) with a long history of development and wide use in clinical applications demonstrate broad-spectrum antibacterial activities through multi-target mechanisms, including disrupting bacterial cell walls and membranes. Owing to methodological limitations, conventional approaches for discovering NAMPs are becoming less effective in identifying new candidates. Therefore, biomimetic antimicrobial peptides (BAMPs) have been developed through structural modifications to enhance stability, safety, and antimicrobial efficacy. This review systematically summarizes recent advances in NAMPs and BAMPs against Gram-positive bacteria, and describes their mechanisms of action, including targeting peptidoglycan precursors in bacterial cell walls, disrupting membrane integrity, and interfering with DNA/RNA to inhibit bacterial growth. This review emphasizes the bacterial trapping mechanism via in situ self-assembly. We also highlight molecular modifications to optimize BAMPs that improve their antimicrobial potential and expand their application in clinic. Finally, we discuss the current limitations and future perspectives of NAMPs and BAMPs, provide valuable guidance for designing next-generation antimicrobial agents.

抗革兰氏阳性菌，包括耐多药菌株，如耐甲氧西林金黄色葡萄球菌（MRSA），由于其坚固的细胞壁结构、生物膜形成和耐药机制，面临着重大挑战。天然抗菌肽（NAMPs）具有悠久的发展历史和广泛的临床应用，通过多靶点机制，包括破坏细菌细胞壁和细胞膜，显示出广谱的抗菌活性。由于方法上的限制，发现NAMPs的传统方法在确定新的候选物方面变得不那么有效。因此，仿生抗菌肽（BAMPs）已经通过结构修饰来提高稳定性、安全性和抗菌功效。本文系统总结了抗革兰氏阳性细菌的NAMPs和BAMPs的最新进展，并描述了它们的作用机制，包括靶向细菌细胞壁的肽聚糖前体、破坏膜完整性、干扰DNA/RNA抑制细菌生长。本文综述了通过原位自组装的细菌捕获机制。我们还强调了优化BAMPs的分子修饰，以提高其抗菌潜力并扩大其在临床中的应用。最后，我们讨论了NAMPs和BAMPs目前的局限性和未来的展望，为下一代抗菌药物的设计提供了有价值的指导。

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引用次数: 0

Long-acting multiple programmed cell death nanoinducers based on polyunsaturated fatty acid supplemented liposomal photosensitizers for enhanced photodynamic immunotherapy 基于多不饱和脂肪酸补充脂质体光敏剂增强光动力免疫治疗的长效多重程序性细胞死亡纳米诱导剂

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123948

Yu Hao , Minming Chen , Yunyun Zhang , Hongchao Yang , Sisi Ling , Chunjie Wang , Yujie Zhu , Ziliang Dong , Chunyan Li , Zhuang Liu , Liangzhu Feng

Photodynamic therapy (PDT) has been investigated for minimal invasive treatment of superficial tumors, but its clinical efficacy is constrained by its immediate light-dependent cytotoxicity, low immunogenicity, and other reasons. Building on the capacity of polyunsaturated fatty acids (PUFAs) to convert short-lived reactive oxygen species into longer-lived, highly cytotoxic lipid radicals, we develop a long-acting liposomal photosensitizer by co-encapsulating chlorin e6 (Ce6) and linoleic acid (LA) with commercial lipids. The resulting LA-Ce6@liposome converts short-lived singlet oxygens to persistent lipid radicals during light exposure, sustaining free LA peroxidation even post-irradiation. Mechanistic studies demonstrate that LA-Ce6@liposome-mediated PDT drives immunogenic ferroptosis and PANoptosis in cancer cells via amplified lipid peroxidation. In preclinical models, this strategy not only inhibits the growth of light-irradiated primary tumors but also activates systemic antitumor immunity, delaying progression of distal metastatic and rechallenged tumors, particularly when synergized with immune checkpoint blockade therapy. This study highlights a streamlined strategy to augment conventional PDT by integrating photosensitizers with PUFAs, offering prolonged tumoradical activity and immune activation.

光动力疗法（PDT）已被研究用于浅表肿瘤的微创治疗，但其临床疗效受到其直接的光依赖性细胞毒性、低免疫原性等原因的限制。基于多不饱和脂肪酸（PUFAs）将短寿命活性氧转化为长寿命、高细胞毒性的脂质自由基的能力，我们开发了一种长效脂质体光敏剂，通过将氯e6 （Ce6）和亚油酸（LA）与商业脂质共包封。由此产生的LA-Ce6@liposome在光照下将短寿命的单线态氧转化为持久的脂质自由基，即使在照射后也能维持自由的LA过氧化。机制研究表明LA-Ce6@liposome-mediated PDT通过放大脂质过氧化作用驱动癌细胞免疫原性铁下垂和PANoptosis。在临床前模型中，该策略不仅可以抑制光照射原发肿瘤的生长，还可以激活全身抗肿瘤免疫，延缓远端转移和再挑战肿瘤的进展，特别是当与免疫检查点阻断疗法协同时。本研究强调了一种简化的策略，通过将光敏剂与pufa结合来增强传统的PDT，提供延长的肿瘤活性和免疫激活。

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引用次数: 0

Solvent-free melt-electrowriting of polycaprolactone-bioceramic composites 聚己内酯-生物陶瓷复合材料的无溶剂熔融电解。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123943

M.L. Eames , A. Weekes , T. Ayyachi , R.A. Pepper , E. Pickering , S. Bell , C. Wu , M.A. Woodruff , T.J. Klein

With increasing surgical cases for bone reconstruction, there is a rising need for advanced synthetic graft materials. In this paper, a novel pipeline for fabricating polycaprolactone (PCL)/bioceramic scaffolds was used to produce micron-fibre composite scaffolds comprising either 25 wt% 45S5 bioglass/45K PCL or 25 wt% molybdenum-doped bioglass/45K PCL (MoBG/PCL). Cryomixing was shown to be an effective method for evenly dispersing high concentrations of finely milled bioceramic particles into PCL without the need for chloroform solvents. The resulting composites had sufficiently low viscosity at 120 °C to be printed using melt electrowriting (MEW). The addition of bioceramic particles into PCL increased the elastic modulus and dramatically reduced the elongation at break. MEW scaffolds printed from a MoBG/PCL composite were shown to effectively support osteoblast cell growth. The cells on MoBG/PCL constructs displayed greater metabolic activity and DNA concentration after 7 days in culture relative to constructs made from unmodified PCL. Concentrated MoBG/PCL composite scaffolds may be a promising pathway for advanced bone tissue scaffolds.

随着骨重建手术病例的增加，对先进合成移植材料的需求也在不断增加。本文提出了一种新型制备聚己内酯/生物陶瓷支架的工艺流程，用于制备含有25% 45S5生物玻璃/45K PCL或25%掺钼生物玻璃/45K PCL （MoBG/PCL）的微米纤维复合支架。低温混合被证明是一种有效的方法均匀分散高浓度的精细研磨的生物陶瓷颗粒到PCL而不需要氯仿溶剂。所得到的复合材料在120°C下具有足够低的粘度，可以使用熔体电解（MEW）进行印刷。生物陶瓷颗粒的加入提高了PCL的弹性模量，并显著降低了断裂伸长率。由MoBG/PCL复合材料打印的新骨支架可以有效地支持成骨细胞的生长。与未经修饰的PCL构建物相比，MoBG/PCL构建物上的细胞在培养7天后显示出更高的代谢活性和DNA浓度。高浓度MoBG/PCL复合支架可能是高级骨组织支架的一个有前途的途径。

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引用次数: 0

A shear-responsive nanosystem engineered from fucoidan targets endothelial for atherosclerosis therapy 由岩藻糖聚糖设计的剪切反应纳米系统用于动脉粥样硬化治疗。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-16 DOI: 10.1016/j.biomaterials.2025.123931

Ruyue Liu , Xuli Ruan , Mengran Guo , Zhongshan He , Yupei Zhang , Tingting Song , Haixing Shi , Xi He , Yaoyao Luo , Yuntao Gao , Min Sun , Chuansheng Huang , Liping Wang , Yunli Zhao , Yong Yuan , Xiangrong Song , Xinchun Wang

Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. In this study, we designed a polysaccharide-based carrier (HF-AF) from fucoidan, featuring a dynamic supramolecular structure. A dynamic supramolecular network was established within this carrier via dynamic supramolecular interactions between hydroxypropyl-β-cyclodextrin and adamantane-methylamine. The anti-inflammatory compound tilianin, formulated into nanocrystals (Til NCs), was then encapsulated to create a shear-responsive nanosystem (HF-AF@Til NCs). The system's primary therapeutic strategy is its response to pathological hemodynamic forces: upon encountering high shear stress at a stenosis, the supramolecular network undergoes dissociation, triggering a mechanically-gated release of the encapsulated Til NCs. This shear-triggered function is complemented by the natural P-selectin affinity of the fucoidan backbone, which facilitates the anchoring of the nanocarrier at the inflamed lesion site. This sophisticated “anchor-and-release” mechanism enables superior drug accumulation precisely at plaque sites. In ApoE^−/− atherosclerotic mice, HF-AF@Til NCs significantly reduced aortic lipid deposition and exerted potent anti-atherosclerotic effects by modulating macrophage polarization, inhibiting the NF-κ-B signaling pathway, and improving lipid profiles. In conclusion, this shear-responsive nanodelivery system, which leverages a targeting polysaccharide, effectively enhances drug accumulation and therapeutic efficacy at atherosclerotic lesions, demonstrating significant potential for the targeted therapy of atherosclerosis.

动脉粥样硬化斑块区域内的血流动力学异常，特别是局部高剪切应力和内皮功能障碍，是药物输送系统干预的新靶点。在这项研究中，我们设计了一种基于岩藻糖聚糖的多糖载体（HF-AF），具有动态的超分子结构。通过羟丙基-β-环糊精与金刚烷-甲胺的动态超分子相互作用，在该载体内建立了动态超分子网络。将抗炎化合物tilianin制成纳米晶体（Til NCs），然后将其封装以创建剪切响应纳米系统（HF-AF@Til NCs）。该系统的主要治疗策略是对病理性血流动力学力的反应：当狭窄处遇到高剪切应力时，超分子网络发生解离，触发机械门控释放包裹的Til NCs。这种剪切触发的功能由岩藻聚糖主链的天然p选择素亲和力补充，这有助于纳米载体在炎症病变部位的锚定。这种复杂的“锚定-释放”机制使药物能够精确地在斑块部位积累。在ApoE-/-动脉粥样硬化小鼠中，HF-AF@Til NCs通过调节巨噬细胞极化、抑制NF-κ- b信号通路和改善脂质谱，显著减少主动脉脂质沉积，并发挥有效的抗动脉粥样硬化作用。综上所述，这种剪切反应纳米递送系统利用靶向多糖，有效地增强了动脉粥样硬化病变的药物积累和治疗效果，显示出动脉粥样硬化靶向治疗的巨大潜力。

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引用次数: 0

Single H2S molecule mediates three-stage antibacterial and immunomodulatory effects in dendritic mesoporous organosilica (DMOS-4MPBA) nanoplatform 枝状介孔有机二氧化硅（DMOS-4MPBA）纳米平台中单个H2S分子介导三期抗菌和免疫调节作用。

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.2025.123941

Zulpya Mahmut , Bingshuai Zhou , Jiao Sun , Wenxin Zheng , Yifan Chen , Jiawei Li , Xinyao Zhang , Yumin Han , Haipeng Liu , Biao Dong

Bacterial infections and inflammatory diseases pose a severe global health threat, driven by antibiotic resistance and dysregulated immune responses. To overcome these challenges, we designed redox-responsive dendritic mesoporous organosilica nanoparticles (DMOS-4MPBA) that utilize a single gaseous molecule - hydrogen sulfide (H₂S) - as a multifunctional therapeutic agent. DMOS-4MPBA releases H₂S selectively within infected microenvironments through glutathione-responsive cleavage of polysulfide bonds. The released H₂S concurrently executes three therapeutic mechanisms: disrupting bacterial energy metabolism and membrane integrity, suppressing quorum sensing to inhibit biofilm formation, and promoting immune regulation via macrophage polarization toward the pro-repair M2 phenotype. Both in vitro and in vivo experiments demonstrate strong antibacterial effects, efficient biofilm disruption, and accelerated wound healing, without compromising biosafety. By integrating antibacterial, anti-biofilm, and immunomodulatory capacities into a single H₂S-releasing platform, we provide a innovative and potent strategy for treating drug-resistant infections and inflammatory diseases.

细菌感染和炎症性疾病在抗生素耐药性和免疫反应失调的驱动下，对全球健康构成严重威胁。为了克服这些挑战，我们设计了氧化还原响应的树突状介孔有机二氧化硅纳米颗粒（DMOS-4MPBA），该纳米颗粒利用单一气体分子硫化氢（H2S）作为多功能治疗剂。DMOS-4MPBA通过谷胱甘肽反应性裂解多硫化物键，在受感染的微环境中选择性释放H2S。释放的H2S同时具有三种治疗机制：破坏细菌能量代谢和膜完整性，抑制群体感应以抑制生物膜的形成，通过巨噬细胞极化促进免疫调节，促进修复M2表型。体外和体内实验均显示出强大的抗菌作用，有效的生物膜破坏，加速伤口愈合，而不影响生物安全性。通过将抗菌、抗生物膜和免疫调节能力整合到一个h2s释放平台中，我们为治疗耐药感染和炎症性疾病提供了一种创新而有效的策略。

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引用次数: 0

Osteosarcoma-on-a-chip model mimicking intra-tumoral heterogeneity to interrogate tumor-associated macrophage reprogramming for immunotherapeutics 骨肉瘤芯片模型模拟肿瘤内异质性，询问肿瘤相关巨噬细胞重编程的免疫治疗。

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.2025.123917

Chitra Jaiswal , Saki Sugihara , Souradeep Dey , Ajay Kumar , Arpita Sharma , Raghvendra Gupta , Biman B. Mandal

The osteosarcoma tumor microenvironment (OS-TME) exhibits pronounced cellular and biophysical heterogeneity, arising from infiltrating immune cells, primarily tumor-associated macrophages (TAMs) and mechanical stress gradients, respectively. TAMs significantly contribute to OS progression through various mechanisms; hence, targeting TAMs could improve treatment outcome in OS patients. This study presents a novel immunocompetent tri-culture osteosarcoma (iTC-OS) model developed using a porous 3D silk fibroin blend-hydroxyapatite (SF-HA) scaffold seeded with human OS cells, human blood derived TAMs, and human umbilical vein endothelial cells (HUVECs). The physiological relevance of the iTC-OS model is further enhanced by integrating into a physiomimetic microfluidic bioreactor (iTC-OS-on-a-chip), featuring dynamic perfusion to simulate intra-tumoral mechanical stress gradient, validated through computational fluid dynamic (CFD). Additionally, we employed pexidartinib and tenalisib to evaluate TAMs reversal in the iTC-OS-on-a-chip model by selectively inhibiting CSF1R and PI3Kγ, respectively. TAMs reprogramming from tumor promoting M2 to tumor suppressing M1 phenotype is confirmed through gene expression analysis of M1 (CCR7, IL-1β, IL-6) and M2 (CD206, CD163, IL-10) macrophage markers, alongside quantification of secreted cytokines via ELISA assay. This advanced iTC-OS-on-a-chip model offers a robust platform for investigating OS-immune cell interactions, enabling pre-clinical evaluation of chemo/immunotherapeutics and improving the translational relevance in OS research.

骨肉瘤肿瘤微环境（OS-TME）表现出明显的细胞和生物物理异质性，分别由浸润性免疫细胞、主要是肿瘤相关巨噬细胞（tam）和机械应力梯度引起。tam通过各种机制显著促进操作系统的发展；因此，靶向tam可以改善OS患者的治疗效果。本研究提出了一种新型的免疫活性三培养骨肉瘤（tc -OS）模型，该模型使用多孔3D丝素蛋白-羟基磷灰石（SF-HA）支架，植入人骨肉瘤细胞、人血源性tam和人脐静脉内皮细胞（HUVECs）。通过集成仿生微流控生物反应器（tc - os -on-a-chip），进一步增强了tc - os模型的生理相关性，该微流控生物反应器采用动态灌注模拟肿瘤内机械应力梯度，并通过计算流体动力学（CFD）验证。此外，我们使用培西达替尼和tenalisib分别通过选择性抑制CSF1R和PI3Kγ来评估tc - os -on-a-chip模型中的tam逆转。通过对M1 （CCR7、IL-1β、IL-6）和M2 （CD206、CD163、IL-10）巨噬细胞标志物的基因表达分析，以及通过ELISA法定量分泌的细胞因子，证实了tam从促肿瘤M2表型重编程为抑肿瘤M1表型。这种先进的tc -OS-on-a-chip模型为研究OS-免疫细胞相互作用提供了一个强大的平台，使化疗/免疫治疗的临床前评估成为可能，并提高了OS研究的翻译相关性。

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