Biomaterials最新文献_第8页

A cannula connecting strategy fostering vascular anastomosis based on mechanical support and biochemical modulation 一种基于机械支持和生化调节的促进血管吻合的插管连接策略

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-11 DOI: 10.1016/j.biomaterials.2025.123850

Shengji Gu , Jian Zhou , Qiang Liu , Paul K. Chu , Zheyi Meng , Yongfeng Shao , Kelvin W.K. Yeung , Guomin Wang

Anastomosis is essential in cardiovascular surgery. However, traditional hand-sewn techniques are technically demanding, and existing sutureless methods often result in complications such as thrombosis and delayed healing due to poor mechanical compliance and insufficient endothelialization. Herein, we propose a cannula connection strategy that combines mechanical and biochemical support via a vascular-shaped polyetheretherketone (PEEK) connector. The PEEK substrate is coated with polydopamine (PDA) and chemically grafted with S-nitroso-N-acetylpenicillamine (SNAP) to enable sustained nitric oxide (NO) release. This approach significantly enhances anastomotic mechanical performance by improving tensile strength and burst pressure, thereby holding promise for reducing operation time and minimizing blood leakage. Compared to non-grafted SNAP coatings (PP–S), the chemically grafted version (PP@S) maintains elevated NO release for over 30 days, effectively modulating the local microenvironment, inhibiting platelet adhesion, and promoting the proliferation and spreading of human umbilical vein endothelial cells (HUVECs). In vivo studies show that the cannula device shortens surgical time by approximately 50 % and significantly decreases intraoperative bleeding. The mechanical structure offers resistance to pressure fluctuations, provides spatial reinforcement, and prevents anastomotic leakage. Concurrently, the biochemical modulation minimizes inflammatory responses and systemic toxicity, facilitating collagen fiber formation and further enhancing structural support. This positive feedback loop results in a 99.04 % anastomotic patency rate two months post-surgery. Overall, this integrated cannula strategy provides an alternative to traditional anastomosis techniques by combining mechanical and biochemical support to enhance anastomotic integrity and facilitate healing.

吻合在心血管手术中是必不可少的。然而，传统的手工缝合技术要求较高，现有的无缝线方法由于机械顺应性差、内皮化不充分等原因，往往导致血栓形成、愈合延迟等并发症。在此，我们提出了一种通过血管状聚醚醚酮（PEEK）连接器结合机械和生化支持的套管连接策略。PEEK底物包被聚多巴胺（PDA），并化学接枝s -亚硝基-n -乙酰青霉胺（SNAP），以实现持续的一氧化氮（NO）释放。该方法通过提高拉伸强度和破裂压力，显著提高吻合口力学性能，从而有望缩短手术时间，最大限度地减少出血。与未移植的SNAP涂层（PP-S）相比，化学移植的SNAP涂层（PP@S）可以维持30天以上的一氧化氮释放，有效调节局部微环境，抑制血小板粘附，促进人脐静脉内皮细胞（HUVECs）的增殖和扩散。体内研究表明，套管装置缩短手术时间约50%，并显著减少术中出血。机械结构可抵抗压力波动，提供空间加固，并防止吻合口渗漏。同时，生化调节减少炎症反应和全身毒性，促进胶原纤维的形成，进一步增强结构支持。术后2个月吻合口通畅率达99.04%。总的来说，这种综合插管策略通过结合机械和生化支持来提高吻合口的完整性和促进愈合，为传统的吻合技术提供了一种选择。

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引用次数: 0

Swift-acting structured lattice-enhanced caramelized sucrose system for painless sedative delivery 快速作用结构晶格增强焦糖无痛镇静输送系统

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-11 DOI: 10.1016/j.biomaterials.2025.123823

Xinting Liang , Lei Yang , Xiuli Chen , Yusheng Gong , Rengui Xu , Qi Zeng , Jiarong Xu , Jiajing Liu , Yuan Liu , Guanyue Li , Linxi He , Wenhao Jiao , Hui Liu , Wei Chen

Dexmedetomidine, known as an exceptionally potent and highly selective α2-adrenergic receptor agonist, is widely used as a safe and effective intravenous sedative agent in both surgical and nonsurgical settings. As the need for an optimized sedative delivery system grows—one that is not only easy to apply but also demonstrates superior efficacy, particularly among pediatric patients and other groups with lower levels of cooperation—innovative delivery methods are increasingly sought. To address this need, we developed a caramelized amorphous sucrose-based lunging microneedle array (CALM), incorporating an advanced Kelvin cell lattice framework. This lattice improves the microneedle array's surface contact with tissues, accelerating and enhancing the drug release process. Additionally, unlike conventional sucrose-based microneedles, which often crystallize and lose mechanical strength, the caramelization process reduces crystallinity, increasing both the stability and structural integrity of the system. These combined features make CALM a highly effective and patient-friendly option for administering dexmedetomidine. Preliminary trials in clinical simulations showed a rapid onset of sedation with minimal discomfort, highlighting its potential as a promising solution for vulnerable populations needing fast and secure sedation.

右美托咪定是一种非常有效和高选择性的α2-肾上腺素能受体激动剂，作为一种安全有效的静脉镇静剂广泛应用于手术和非手术环境。随着对一种优化的镇静输送系统的需求的增长——一种不仅易于使用，而且具有优越疗效的系统，特别是在儿科患者和其他合作水平较低的群体中——越来越多地寻求创新的输送方法。为了满足这一需求，我们开发了一种基于焦糖无定形蔗糖的弓状微针阵列（CALM），结合了先进的开尔文细胞晶格框架。这种晶格改善了微针阵列与组织的表面接触，加速和增强了药物释放过程。此外，与传统的基于蔗糖的微针（经常结晶并失去机械强度）不同，焦糖化过程降低了结晶度，增加了系统的稳定性和结构完整性。这些综合功能使CALM成为一个非常有效和患者友好的选择，用于管理右美托咪定。临床模拟的初步试验显示，镇静作用迅速起效，不适最小，突出了其作为需要快速安全镇静的弱势群体的有希望的解决方案的潜力。

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引用次数: 0

Chemo-immunotherapeutic potential of Lactobacillus rhamnosus GG and its bioengineering for cancer therapy 鼠李糖乳杆菌GG的化学免疫治疗潜力及其在肿瘤治疗中的生物工程应用。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-10 DOI: 10.1016/j.biomaterials.2025.123848

Zhaonan Liu , Qing Guan , Jianfeng Xin , Wei Tang , Yu Chen , Jiaying Zhang , Junjie Chen , Shijie Bi , Peng Wang , Jun Liu

Bacteriotherapy holds great promise for cancer treatment, yet few bacterial agents have progressed to clinical application. Inspired by the acidic growth conditions of Lactobacillus rhamnosus GG (LGG), which resemble the tumor microenvironment, we systematically investigated its intrinsic anti-tumor potential. LGG demonstrated acid-environment tropism, strong adhesion to tumor cells, and active penetration into deep tumor tissues. Both LGG and its secretions exhibited potent cytotoxicity against various tumor cell lines, associated with mitochondrial dysfunction and apoptosis, likely due to acidification of the surrounding environment. Furthermore, LGG competitively inhibited tumor-promoting bacteria and activated immune responses by promoting M1-type macrophage polarization and dendritic cell maturation. To enhance its therapeutic efficacy, we further developed a biohybrid system by conjugating paclitaxel-loaded poly (lactic-co-glycolic acid) nanoparticles to LGG (PTX-NPs-LGG), enabling both targeted chemotherapy and bacteriotherapy. Additionally, a thermo-sensitive hydrogel was employed for peritumoral delivery, ensuring sustained release and localized activity. In the 4T1 breast tumor lung metastasis model and the B16F10 tumor postoperative recurrence model, PTX-NPs-LGG@gel exhibited superior anti-tumor efficacy with favorable safety profiles. These findings highlight the potential of LGG-based biohybrids as a safe and effective platform for chemo-immunotherapy in cancer treatment.

细菌疗法在癌症治疗中具有很大的前景，但很少有细菌制剂能够发展到临床应用。受鼠李糖乳杆菌GG （Lactobacillus rhamnosus GG， LGG）类似肿瘤微环境的酸性生长条件的启发，我们系统地研究了其内在的抗肿瘤潜能。LGG表现出嗜酸性，对肿瘤细胞有较强的粘附性，并能积极渗透到肿瘤深部组织。LGG及其分泌物对多种肿瘤细胞系都表现出强大的细胞毒性，与线粒体功能障碍和凋亡有关，可能是由于周围环境的酸化。此外，LGG通过促进m1型巨噬细胞极化和树突状细胞成熟，竞争性地抑制促瘤细菌并激活免疫反应。为了提高其治疗效果，我们进一步开发了一种生物杂交系统，通过将负载紫杉醇的聚乳酸-羟基乙酸纳米颗粒偶联到LGG （PTX-NPs-LGG）上，实现靶向化疗和细菌治疗。此外，热敏水凝胶用于肿瘤周围递送，确保持续释放和局部活性。在4T1乳腺肿瘤肺转移模型和B16F10肿瘤术后复发模型中，PTX-NPs-LGG@gel具有较好的抗肿瘤疗效和良好的安全性。这些发现突出了以lgg为基础的生物杂交体作为一种安全有效的癌症化疗免疫治疗平台的潜力。

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引用次数: 0

Mo2C nanozyme targets citrate synthase to treat acute kidney injury through alleviating oxidative stress and dysfunction of energy metabolism Mo2C纳米酶靶向柠檬酸合酶，通过减轻氧化应激和能量代谢功能障碍治疗急性肾损伤。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-08 DOI: 10.1016/j.biomaterials.2025.123845

Wei Wei , Yuyi Zhu , Xiaoqin Shui , Caihong Liu , Yongxiu Huang , Jinglei Ren , Chang Liu , Letian Yang , Liang Ma , Meng Gong , Ping Fu , Dingkun Zhang , Yuliang Zhao

Acute kidney injury (AKI), characterized by rapid renal dysfunction, lacks effective therapies due to its complex pathophysiology involving oxidative stress and mitochondrial damage. Molybdenum carbide (Mo₂C) nanozymes show promise through their tunable catalytic properties and reactive oxygen species (ROS)-scavenging capacity. To elucidate the metabolic basis of their therapeutic effects, we employed metabolomics analysis for molecular-level metabolic profiling, combined with evaluation in lipopolysaccharide (LPS)-, cisplatin (CP)-, and ischemia-reperfusion injury (IRI)-induced AKI models and TCMK-1 cell validation. Key findings demonstrated that Mo₂C restored renal function, reduced oxidative damage/apoptosis, and preserved mitochondrial integrity. Metabolomic mechanistic investigation revealed normalization of dysregulated pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. Consistently, in LPS-challenged TCMK-1 cells, Mo₂C suppressed ROS, attenuated apoptosis, reduced inflammation, and specifically stabilized TCA cycle function. Most importantly, inhibition of citrate synthase causally demonstrated that Mo₂C's renoprotection depends on TCA cycle modulation. These integrated findings establish Mo₂C nanozymes as a novel AKI treatment paradigm through TCA cycle homeostasis restoration, with significant translational potential. To realize this potential, future studies focusing on comprehensive safety profiling and clinical validation may facilitate the translation of Mo₂C nanozymes into therapeutic applications for AKI and related renal disorders.

急性肾损伤（Acute kidney injury， AKI）以快速肾功能障碍为特征，其复杂的病理生理机制涉及氧化应激和线粒体损伤，缺乏有效的治疗。碳化钼（Mo2C）纳米酶具有可调节的催化性能和清除活性氧（ROS）的能力，具有广阔的应用前景。为了阐明其治疗作用的代谢基础，我们采用代谢组学分析进行分子水平的代谢分析，并结合脂多糖(LPS)-、顺铂(CP)-和缺血再灌注损伤（IRI）诱导的AKI模型的评估和TCMK-1细胞验证。主要研究结果表明，Mo2C可恢复肾功能，减少氧化损伤/凋亡，并保持线粒体完整性。代谢组学机制研究显示，包括糖酵解、三羧酸（TCA）循环和氧化磷酸化在内的失调途径正常化。一致地，在lps刺激的TCMK-1细胞中，Mo2C抑制ROS，减轻凋亡，减少炎症，并特异性稳定TCA循环功能。最重要的是，柠檬酸合成酶的抑制表明，Mo2C的保护作用依赖于TCA循环调节。这些综合研究结果表明，Mo2C纳米酶通过恢复TCA循环稳态，作为一种新的AKI治疗范例，具有重要的转化潜力。为了实现这一潜力，未来的研究将重点放在全面的安全性分析和临床验证上，这可能有助于Mo2C纳米酶转化为AKI和相关肾脏疾病的治疗应用。

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引用次数: 0

Sericin-based dual-module microspheres promote periodontal regeneration through four-dimensional microenvironment remodeling 丝胶蛋白双模微球通过四维微环境重塑促进牙周再生。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-07 DOI: 10.1016/j.biomaterials.2025.123843

Peirong Zhou , Xuemin Ma , Yajuan Hu , Yongcen Chen , Huiyue Wang , Tao Wang , Junliang Chen , Rui Cai , Yun He , Gang Tao

Periodontitis, a chronic inflammatory disease marked by oxidative stress, dysregulated inflammation, and alveolar bone resorption, remains a major oral health challenge due to conventional therapy's limited spatiotemporal control over tissue repair. To address this, we developed a sericin-based dual-module microsphere system (SeHA@EC): an inner pro-angiogenic/osteogenic module (ZnSr–Se-HA nanoparticles) and an outer anti-oxidant/anti-inflammatory module (EGCG-Ce Metal–phenolic networks, MPNs). The outer EGCG-Ce MPNs mitigate acute inflammation by scavenging ROS and modulating macrophage polarization toward M2, while the inner ZnSr–Se-HA module sequentially drives angiogenesis and osteogenesis during tissue repair. In vitro investigations demonstrated that SeHA@EC attenuated intracellular ROS levels, stabilized mitochondrial membrane potential, directed macrophage polarization toward the M2 phenotype via activating the SIRT1/FOXO3a/SOD-CAT axis and inhibiting NF-κB signaling, while additionally promoting angiogenesis and osteogenic differentiation of hPDLSCs. In vivo experiments further validated SeHA@EC's therapeutic efficacy in a rat periodontitis model: it significantly reduced intracellular ROS levels, suppressed pro-inflammatory cytokine expression (TNF-α, iNOS), upregulated anti-inflammatory marker expression (arginase, CD206), enhanced angiogenic and osteogenic activity, suppressed osteoclast activity, and accelerated alveolar bone regeneration. By overcoming the single-modal limitations of conventional biomaterials, this dual-module system establishes a microenvironment remodeling strategy for periodontal regeneration through spatiotemporal regulation of the pathological cascade.

牙周炎是一种以氧化应激、炎症失调和牙槽骨吸收为特征的慢性炎症性疾病，由于常规治疗对组织修复的时空控制有限，仍然是口腔健康的主要挑战。为了解决这个问题，我们开发了一种基于丝胶蛋白的双模块微球系统（SeHA@EC）：内部促血管生成/成骨模块（ZnSr-Se-HA纳米颗粒）和外部抗氧化/抗炎模块（EGCG-Ce金属酚网络，mpn）。外层的EGCG-Ce mpn通过清除ROS和调节巨噬细胞向M2的极化来减轻急性炎症，而内部的ZnSr-Se-HA模块在组织修复过程中依次驱动血管生成和骨生成。体外研究表明，SeHA@EC降低细胞内ROS水平，稳定线粒体膜电位，通过激活SIRT1/FOXO3a/SOD-CAT轴和抑制NF-κB信号传导，引导巨噬细胞向M2表型极化，同时促进hPDLSCs的血管生成和成骨分化。体内实验进一步验证了SeHA@EC在大鼠牙周炎模型中的治疗效果：显著降低细胞内ROS水平，抑制促炎细胞因子（TNF-α、iNOS）表达，上调抗炎标志物（精氨酸酶、CD206）表达，增强血管生成和成骨活性，抑制破骨细胞活性，加速牙槽骨再生。该双模系统克服了传统生物材料单模态的局限性，通过病理级联的时空调节，建立了牙周再生的微环境重塑策略。

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引用次数: 0

Selective killing of cancer-associated fibroblasts by ultrasound-mediated mechanical forces 超声介导的机械力选择性杀伤癌症相关成纤维细胞。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-07 DOI: 10.1016/j.biomaterials.2025.123844

Gomathi Sankar , Arka Roy Choudhury , Rashmita Luha , Akshay Kumar , Ketan Kulkarni , Mingxi Yao , Rudra Pratap , Aravind Kapali , Ajay Tijore

Recent studies show that stretch/ultrasound (US)-generated mechanical forces cause selective apoptosis in several cancer cells, tumor organoids and animal models without damaging normal cells. Cancer-associated fibroblasts (CAFs) are an integral tumor microenvironment (TME) constituent. They display altered biomechanical properties similar to cancer cells, such as matrix secretion and its remodelling, chemokine secretion, and high contractile force generation. We thus test the effect of US-mediated mechanical forces on patient-derived CAF survival. Surprisingly, US treatment causes CAF apoptosis (mechanoptosis) through a calcium-activated apoptotic pathway but not in normal fibroblasts. MicroRNA-21 (miR-21) secreted by primary cancer cells suppresses the mechanosensory cytoskeletal protein tropomyosin 2.1 (Tpm2.1) in CAFs. This Tpm2.1 depletion in CAFs is responsible for mechanoptosis. Interestingly, normal fibroblasts behave similarly when Tpm2.1 was depleted. Further, 3D gel contractility and migration assay confirm that a prolonged US treatment disrupts myosin IIA-mediated contractility, which CAFs primarily use to support cancer invasion. Since US treatment causes mechanoptosis and reduces contractility, this approach could be used to develop ultrasound-based CAF-targeting therapy to augment cancer treatment.

最近的研究表明，拉伸/超声（US）产生的机械力在几种癌细胞、肿瘤类器官和动物模型中引起选择性凋亡，而不损害正常细胞。癌症相关成纤维细胞（CAFs）是一个完整的肿瘤微环境（TME）组成部分。它们表现出与癌细胞相似的改变的生物力学特性，如基质分泌及其重塑、趋化因子分泌和高收缩力产生。因此，我们测试了us介导的机械力对患者源性CAF存活的影响。令人惊讶的是，US治疗通过钙激活的凋亡途径导致CAF凋亡（机械凋亡），但在正常成纤维细胞中却没有。原发癌细胞分泌的MicroRNA-21 （miR-21）抑制CAFs中机械感觉细胞骨架蛋白原肌球蛋白2.1 （Tpm2.1）。CAFs中的Tpm2.1耗竭是机械失稳的原因。有趣的是，当Tpm2.1缺失时，正常成纤维细胞表现相似。此外，3D凝胶收缩性和迁移试验证实，长期的US治疗会破坏肌球蛋白iia介导的收缩性，而肌球蛋白iia介导的收缩性主要用于支持癌症侵袭。由于US治疗会导致机械下垂并降低收缩力，因此该方法可用于开发基于超声的caf靶向治疗，以增强癌症治疗。

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引用次数: 0

Pro-osteogenic implants inhibit local excessive B cell maturation via neutrophils-derived CD52 signaling to enhance osseointegration 促骨植入物通过中性粒细胞来源的CD52信号抑制局部过度的B细胞成熟，以增强骨整合。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-07 DOI: 10.1016/j.biomaterials.2025.123841

Yangbo Xu , Congrui Zhao , Jingyao Gong, Yanqi Chen, Hui Wang, Han Zhu, Antian Xu, Fuming He

Metallic implants have been widely utilized in orthopedics surgery. Osseointegration is a local tradeoff between the inflammatory microenvironment and repair processes surrounding implants, driven by innate and adaptive immune cells. B cells contribute to bone metabolism during fracture healing and in several bone-destructive diseases, such as rheumatoid arthritis and periodontitis. However, the participation of B cells in implantable biomaterials-mediated osseointegration has not been extensively studied, even though they occupy a significant proportion at the injury site. Here, we characterized the heterogeneity of immune cells surrounding bone implants and identified the crucial role of infiltrating B cells based on the implantation model in murine tibias via single-cell RNA sequencing (scRNA-seq). Excessive B cell maturation was observed around implants with poor bone formation, compared with pro-osteogenic implants. Additionally, targeting mature B cells via anti-CD20 depletion antibody restored the damaged osseointegration. Differential expression genes analysis and the application of neutralizing antibodies demonstrated that up-regulated Tnfa and Il1b in B cell maturation attenuated the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). In terms of potential mechanisms, we discovered that pro-osteogenic implants indirectly suppressed local B cell maturation through neutrophils-derived CD52-SiglecG axis, inhibiting downstream ERK1/2 and NF-κB signaling pathways. In summary, our study underscores the pivotal role of B cells in osseointegration and offers novel insights into a promising therapeutic avenue for developing bone biomaterials with immunomodulatory properties and promoting peri-implant bone regeneration.

金属植入物在骨科手术中得到了广泛的应用。骨整合是炎症微环境和种植体周围修复过程之间的局部权衡，由先天和适应性免疫细胞驱动。B细胞在骨折愈合和一些骨破坏性疾病（如类风湿关节炎和牙周炎）中参与骨代谢。然而，B细胞在可植入生物材料介导的骨整合中的参与尚未得到广泛的研究，尽管它们在损伤部位占据了很大的比例。在这里，我们通过单细胞RNA测序（scRNA-seq）表征了骨植入物周围免疫细胞的异质性，并确定了基于植入模型的浸润B细胞在小鼠胫骨中的关键作用。与促成骨种植体相比，在成骨不良的种植体周围观察到过度的B细胞成熟。此外，通过抗cd20耗尽抗体靶向成熟B细胞可以恢复受损的骨整合。差异表达基因分析和中和抗体的应用表明，在B细胞成熟过程中上调Tnfa和Il1b可减弱骨髓间充质基质细胞（BMSCs）的成骨分化。就潜在机制而言，我们发现促骨植入物通过中性粒细胞衍生的CD52-SiglecG轴间接抑制局部B细胞成熟，抑制下游ERK1/2和NF-κB信号通路。总之，我们的研究强调了B细胞在骨整合中的关键作用，并为开发具有免疫调节特性的骨生物材料和促进种植体周围骨再生提供了新的治疗途径。

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引用次数: 0

A versatile device for in vitro magnetomechanical scaffold stimulation and enhancement of osteochondral differentiation of hMSCs 一种体外磁机械支架刺激和增强骨髓间充质干细胞骨软骨分化的多功能装置

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-07 DOI: 10.1016/j.biomaterials.2025.123847

Maria Kalogeropoulou , Sophia Dalfino , Milad Takhsha , Andrada Serafim , Izabela-Cristina Stancu , Gianluca Tartaglia , Pierpaolo Fucile , Lorenzo Moroni

Physical stimuli have received significant attention, owing to their capacity to create more biomimetic niches. While dynamic mechanical loading has shown promise in promoting osteogenic and chondrogenic differentiation, magnetic fields have recently emerged as another potential stimulus. However, the combined effect of magnetomechanical - simultaneous magnetic and mechanical-stimulation on osteochondral tissue regeneration, remains largely unexplored. Moreover, a significant discrepancy exists across systems for magnetic stimulation in vitro, hindering cross-study comparison. Addressing these challenges, we developed a versatile, high-throughput device capable of delivering controlled magnetomechanical stimulation to 3D structures in vitro. When paired with magnetoactive, 3D printed scaffolds with low (mPLC5%) or high (mPLC20%) magnetic content, this system enabled the application of oscillating magnetic fields (0–300 mT) causing a cyclic mechanical displacement (0–2 μm). Magnetomechanical stimulation increased the expression of key osteogenic markers, including a 3-fold increase of alkaline phosphatase (ALP) and a 2-fold increase in osteocalcin concentration in mPLC5% scaffolds. Additionally, stimulated mPLC5% scaffolds showed a 2-fold increase in the relative expression of mechanotransduction markers compared to the mPLC20% condition. Moreover, a 3-fold increase in the expression of Collagen II and Aggrecan was observed in the stimulated mPLC20% scaffolds compared to their static counterparts, showing that this condition could be a potentially good candidate for chondrogenic commitment. Our findings suggest the presence of an optimal window for directing osteogenic or chondrogenic commitment, driven by the degree of cyclic deformation and the presence of the external oscillating magnetic field, in the absence of other differentiation stimuli.

由于物理刺激能够创造更多的仿生生态位，因此受到了极大的关注。虽然动态机械载荷已显示出促进成骨和软骨分化的希望，但磁场最近成为另一种潜在的刺激。然而，磁机械联合作用-同时磁和机械刺激对骨软骨组织再生的影响，在很大程度上仍未被探索。此外，体外磁刺激系统之间存在显著差异，阻碍了交叉研究比较。为了应对这些挑战，我们开发了一种多功能、高通量的设备，能够在体外对3D结构进行可控的磁机械刺激。当与低（mPLC5%）或高（mPLC20%）的磁活性3D打印支架配对时，该系统使振荡磁场（0-300 mT）的应用产生循环机械位移（0-2 μm）。磁机械刺激增加了关键成骨标志物的表达，包括碱性磷酸酶（ALP）增加3倍，mPLC5%支架中骨钙素浓度增加2倍。此外，与mPLC20%的支架相比，受刺激的mPLC5%支架的机械转导标志物的相对表达增加了2倍。此外，在受刺激的mPLC20%支架中，与静态支架相比，胶原II和Aggrecan的表达增加了3倍，这表明这种情况可能是软骨形成的潜在候选者。我们的研究结果表明，在没有其他分化刺激的情况下，存在一个由循环变形程度和外部振荡磁场的存在驱动的指导成骨或软骨承诺的最佳窗口。

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引用次数: 0

Biomimetic nanoplatform-mediated CRISPR/Cas9 delivery for dual-pathway metabolic blockade in head and neck squamous cell carcinoma 仿生纳米平台介导的CRISPR/Cas9递送用于头颈部鳞状细胞癌的双途径代谢阻断。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-07 DOI: 10.1016/j.biomaterials.2025.123837

Ting Fang , Chang Peng , Rui Ding , Yinzhen Fan , Jiajia Jia , Jiajie Chen , XinHang Zhang , Dongkai Wang , Ji Li

Head and neck squamous cell carcinoma (HNSCC) continues to exhibit a poor prognosis, largely due to late diagnosis and the development of cisplatin resistance. Tumor proliferation in HNSCC is closely associated with upregulation of key glycolytic enzymes. However, monotherapeutic targeting of glycolysis paradoxically enhances compensatory glutaminolysis via glutamate overproduction. To overcome this metabolic adaptation, we developed biomimetic nanoparticles P-T-p@CM, fabricated from the pH/reduction dual-responsive copolymer poly(lactic acid)-polyhistidine-polyethylenimine (PLA-pHis-ss-PEI). This nanoplatform enables coordinated co-delivery of telaglenastat (a glutaminase 1 (GLS1) inhibitor) and a CRISPR-Cas9 plasmid encoding sgRNA targeting HIF-1α. This system utilizes homologous cancer cell membrane coating for precise tumor homing, with stimuli-responsive release enabling simultaneous dual metabolic blockade: CRISPR-mediated HIF-1α knockout attenuates glycolysis while telaglenastat suppresses glutamine-to-glutamate conversion. Metabolic analyses confirmed significant reduction in Glycolysis proton efflux rate (GlycoPER), the oxygen consumption rate (OCR) and ATP generation, as well as the related metabolites including the lactate production and glutamate. This dual-starvation strategy depleted energy reserves and biosynthetic precursors, inducing severe metabolic disruption. Notably, in vivo studies showed a 90 % tumor inhibition rate (TIR) after 15 days of treatment, through enhanced apoptosis, reduced proliferation, and tumor glucose/glutamate depletion. Collectively, P-T-p@CM establishes a paradigm-shifting approach to disrupt metabolic compensation in the treatment of HNSCC.

头颈部鳞状细胞癌（HNSCC）继续表现出较差的预后，主要是由于晚期诊断和顺铂耐药性的发展。HNSCC的肿瘤增殖与关键糖酵解酶的上调密切相关。然而，糖酵解的单一治疗靶向矛盾地通过谷氨酸过量产生增强代偿性谷氨酰胺解。为了克服这种代谢适应，我们开发了仿生纳米颗粒P-T-p@CM，由pH/还原双响应共聚物聚乳酸-聚组氨酸-聚乙烯亚胺（PLA-pHis-ss-PEI）制成。该纳米平台能够协同递送telaglenastat（谷氨酰胺酶1 （GLS1）抑制剂）和编码sgRNA靶向HIF-1α的CRISPR-Cas9质粒。该系统利用同源癌细胞膜涂层进行精确的肿瘤归巢，具有刺激响应性释放，同时实现双重代谢阻断：crispr介导的HIF-1α敲除减弱糖酵解，而telaglenastat抑制谷氨酰胺到谷氨酸的转化。代谢分析证实糖酵解质子外排率（GlycoPER）、耗氧率（OCR）和ATP生成以及相关代谢产物（乳酸生成和谷氨酸）显著降低。这种双重饥饿策略耗尽了能量储备和生物合成前体，导致严重的代谢中断。值得注意的是，体内研究显示，经过15天的治疗，通过增强细胞凋亡，减少增殖和肿瘤葡萄糖/谷氨酸消耗，肿瘤抑制率（TIR）达到90%。总之，P-T-p@CM建立了一种范式转换的方法来破坏HNSCC治疗中的代谢代偿。

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引用次数: 0

Nerve growth factor-targeting nanocluster-antibody-drug conjugates for intravesical precision theranostics of interstitial cystitis 神经生长因子靶向纳米簇-抗体-药物偶联物膀胱内精确治疗间质性膀胱炎。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-11-05 DOI: 10.1016/j.biomaterials.2025.123840

Zhijun Lin , Wanyan Wang , Dingxin Liu , Qiwei Liu , Zhifeng Xu , Xiangfu Zhou , Xiaodong Zhang , Yong Huang , Qi Zhao , Zhiming Wu , Jiang Yang

Interstitial cystitis (IC) is a chronic inflammatory bladder disorder lacking timely diagnostic and therapeutic options. Here, we propose a unitary theranostic nanocluster-antibody-drug conjugate (NADC) by covalently attaching dihydroorotate dehydrogenase inhibitors (DHODHi) and ultrasmall gold quantum clusters (AuQCs) to a nerve growth factor (NGF) antagonistic antibody, with multimodality imaging contrasts. Combining anti-inflammatory effects from all individual components, intravesical NADC specifically homed to mucosal lesions with tissue-residing NGF overexpression in the voided bladder, where it neutralized and formed immunocomplexes with secreted NGF to be intracellularly internalized by inflammatory macrophages for payload release through the FcγR-mediated pathway. NADC alleviated inflammation in chronic, acute, and prophylactic IC models of rats, as revealed by behavioral and pathological evaluations. Transcriptomics unveiled cytokine modulation and concomitant inhibition of perturbed IL-17, NF-κB, TNF, and JAK-STAT signaling pathways. Notably, NADC indirectly remodeled the host bladder microbiota by differentially varying anti-inflammatory and pro-inflammatory bacterial diversities. Distinct from conventional nanoparticles conjugated with antibodies or drugs, NADC relies on the antibody framework, outperforms clinical standard-of-care agents, and represents emerging precision medicine with translational potential for IC theranostics in clinical practice.

间质性膀胱炎是一种慢性炎性膀胱疾病，缺乏及时的诊断和治疗选择。在这里，我们提出了一种单一的治疗纳米簇-抗体-药物偶联物（NADC），通过共价结合二氢羟酸脱氢酶抑制剂（DHODHi）和超小金量子簇（auqc）与神经生长因子（NGF）拮抗抗体，并进行多模态成像对比。结合所有个体成分的抗炎作用，膀胱内NADC特异性地定位于空膀胱组织中存在的NGF过表达的粘膜病变，在那里它与分泌的NGF中和并形成免疫复合物，被炎症巨噬细胞内化，通过fc γ r介导的途径释放有效载荷。行为学和病理学评价显示，NADC可减轻慢性、急性和预防性IC模型大鼠的炎症反应。转录组学揭示了细胞因子调节和伴随的抑制受干扰的IL-17、NF-κB、TNF和JAK-STAT信号通路。值得注意的是，NADC通过不同的抗炎和促炎细菌多样性间接重塑了宿主膀胱微生物群。与传统的纳米颗粒结合抗体或药物不同，NADC依赖于抗体框架，优于临床标准治疗药物，并代表了在临床实践中具有转化IC治疗潜力的新兴精准医学。

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引用次数: 0