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Correction: Fibromodulin facilitates the osteogenic effect of Masquelet's induced membrane by inhibiting the TGF-β/SMAD signaling pathway. 更正:纤维调节素通过抑制TGF-β/SMAD信号通路促进Masquelet诱导膜的成骨作用。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-12 DOI: 10.1039/d6bm90082h
Kai Wang, Ming Zhou, Yuanshu Zhang, Yesheng Jin, Yuan Xue, Dong Mao, Yongjun Rui

Correction for 'Fibromodulin facilitates the osteogenic effect of Masquelet's induced membrane by inhibiting the TGF-β/SMAD signaling pathway' by Kai Wang et al., Biomater. Sci., 2024, 12, 1898-1913, https://doi.org/10.1039/D3BM01665J.

更正“纤维调节素通过抑制TGF-β/SMAD信号通路促进Masquelet诱导膜的成骨作用”(王凯等,Biomater)。科学。, 2024, 12, 1898-1913, https://doi.org/10.1039/D3BM01665J。
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引用次数: 0
Biological evaluation and in vivo degradation steady-state endpoint exploration of a sodium alginate/poloxamer composite temperature-sensitive embolic gel for tumors. 海藻酸钠/波洛沙姆复合温度敏感肿瘤栓塞凝胶的生物学评价和体内降解稳态终点探索。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-12 DOI: 10.1039/d6bm00953k
Meng Zhong, Jiuchun Zhang, Sibo Cheng, Chong Shu, Tengjisi, Zixian Yang, Yuancen Li, Tun Yuan

In the regulatory science of absorbable medical devices, traditional in vivo degradation evaluations are often hindered by lengthy evaluation cycles and ambiguous standards. This restricts the research, development, and translation of novel embolic materials. The lack of an evaluation system to determine whether tissue responses have reached a "degradation steady-state endpoint" is particularly critical. This study systematically evaluated the biological efficacy and in vivo degradation steady state of a composite temperature-sensitive embolic agent based on sodium alginate and poloxamer. This gel undergoes a spontaneous phase transition at body temperature. Combined with a dual-lumen microcatheter delivery technique, it achieves instant crosslinking with calcium ions, exhibiting excellent resistance to blood flow washout. The embolization results in canine hepatic and renal artery models and rabbit renal tumor in situ models confirmed the efficacy of this composite gel as a tumor embolic agent. Its ability to induce coagulation necrosis and apoptosis in tumor tissues outperformed current clinical lipiodol and polyvinyl alcohol (PVA) microspheres. A six-month porcine hepatic/renal artery study examined residual implant-like material, recanalization, local histopathology, selected endothelial markers, and systemic observations. Under the tested protocols, the PS gel occluded target vessels and showed good biological safety. In pigs, implant-like material remained at six months, while selected histological injury and inflammatory measures were lower than at earlier terminal time points. Histopathological results indicated that local macrophage phagocytosis and inflammatory responses in the target vessels were active between 1 and 3 months. By 6 months, the inflammation level had significantly subsided to a mild state, with concurrent reductions in fibrosis and fatty infiltration. This was accompanied by prominent tissue repair and remodeling, marking a smooth transition of the tissue response toward a steady state. The results support a candidate criteria-based framework for future prospective evaluation. The results justify further formulation characterization, controlled long-term studies, and component-resolved degradation analysis.

在可吸收医疗器械的监管科学中,传统的体内降解评估往往受到冗长的评估周期和模糊的标准的阻碍。这限制了新型栓塞材料的研究、开发和转化。缺乏一个评估系统来确定组织反应是否达到“降解稳态终点”是特别关键的。本研究系统评价了海藻酸钠和波洛沙姆复合温度敏感栓塞剂的生物有效性和体内降解稳态。这种凝胶在体温下发生自发相变。结合双腔微导管输送技术,它与钙离子实现即时交联,表现出优异的抗血流冲洗性。犬肝、肾动脉模型和兔肾原位肿瘤模型的栓塞结果证实了该复合凝胶作为肿瘤栓塞剂的有效性。其诱导肿瘤组织凝固坏死和凋亡的能力优于目前临床使用的脂醇和聚乙烯醇(PVA)微球。一项为期六个月的猪肝/肾动脉研究检查了残留的植入物样物质、再通、局部组织病理学、选定的内皮标志物和全身观察。在实验方案下,PS凝胶对靶血管有良好的封堵作用,具有良好的生物安全性。在猪中,植入物样物质在6个月时仍然存在,而选择的组织学损伤和炎症指标低于早期的终端时间点。组织病理学结果显示,1 ~ 3个月时靶血管内局部巨噬细胞吞噬和炎症反应活跃。6个月时,炎症水平明显消退至轻度状态,同时纤维化和脂肪浸润减少。这是伴随着著名组织修复和重构,标志着平稳过渡的组织反应向稳定状态。研究结果为未来的前瞻性评价提供了候选标准框架。结果证明了进一步的配方表征,控制长期研究和成分分解降解分析。
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引用次数: 0
Correction: Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production. 纠正:鸢尾素通过抑制氧化应激和RANKL的产生,将骨生成和破骨细胞生成结合起来,保护磨损颗粒诱导的骨溶解。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-09 DOI: 10.1039/d6bm90083f
Sihan Hu, Yuan Xue, Jiachen He, Chichi Chen, Jie Sun, Yesheng Jin, Yuanshu Zhang, Qin Shi, Yongjun Rui

Correction for 'Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production' by Sihan Hu et al., Biomater. Sci., 2021, 9, 5791-5801, https://doi.org/10.1039/D1BM00563D.

对“鸢尾素通过抑制氧化应激和RANKL生成,将成骨和破骨细胞生成结合起来,以保护磨损颗粒诱导的骨溶解”的修正(Sihan Hu等,Biomater)。科学。, 2021, 9, 5791-5801, https://doi.org/10.1039/D1BM00563D。
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引用次数: 0
Correction: Harnessing (-)-epigallocatechin-3-gallate (EGCG) with chitosan-coated liposomes to modulate the radiation effect in cancer cells through alteration in the miR-139-5p-β-catenin axis. 校正:利用(-)-表没食子儿茶素-3-没食子酸酯(EGCG)和壳聚糖包被脂质体通过改变miR-139-5p-β-catenin轴来调节癌细胞中的辐射效应。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-09 DOI: 10.1039/d6bm90081j
Sulagna Dutta, Tridib Banerjee, Arindom Halder, Moupriya Mukherjee, Krishnendu Manna, Goutam Pramanik, Kamalika Sen, Arghya Adhikary, Goutam Ghosh, Ujjal Das

Correction for 'Harnessing (-)-epigallocatechin-3-gallate (EGCG) with chitosan-coated liposomes to modulate the radiation effect in cancer cells through alteration in the miR-139-5p-β-catenin axis' by Sulagna Dutta et al., Biomater. Sci., 2026, https://doi.org/10.1039/d6bm00597g.

Sulagna Dutta等人,Biomater对“利用(-)-表没食子儿茶素-3-没食子酸酯(EGCG)与壳聚糖包被脂质体通过改变miR-139-5p-β-catenin轴来调节癌细胞中的辐射效应”的修正。科学。, 2026, https://doi.org/10.1039/d6bm00597g。
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引用次数: 0
A poly(lipoic acid)-based binary elastomeric patch for treating oral leukoplakia. 一种用于治疗口腔白斑的聚硫辛酸二元弹性贴剂。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-09 DOI: 10.1039/d6bm01100d
Fushuo Wang, Fangze Guo, Changqing Yuan, Xinrui Zhao, Chunyan Cui, Qihui Zhou, Wenguang Liu

Oral leukoplakia (OLK) is a prevalent oral potentially malignant disorder. Targeting the core pathogenesis of OLK, we herein develop a poly(lipoic acid)-based bioadhesive elastomeric patch via a one-step solvent evaporation strategy by integrating lipoic acid with lauroyl arginate ethyl ester hydrochloride, an FDA-approved antimicrobial agent. In this binary system, LAE self-assembles into nanomicelles with outwardly radiating guanidino groups acting as "multi-armed grippers" that suppress room-temperature depolymerization of PolyLA through multiple hydrogen bonds and electrostatic interactions with carboxyl groups. The abundant carboxyl groups on the elastomer surface provide excellent wet tissue adhesion suitable for the dynamic oral environment. Surfactants with distinct terminal groups are further applied to validate the universality of this binary design strategy and to clarify the regulatory effects of intermolecular interaction strength on material stability, crystallinity and mechanical performance. In vitro biological evaluations demonstrate that the PolyLA/LAE patch can efficiently scavenge ROS, inhibit C. albicans proliferation, and induce apoptosis of dysplastic oral keratinocytes, while maintaining favorable biocompatibility. In a rat OLK model, the patch exhibits satisfactory therapeutic outcomes that are comparable to clinical vitamin A ointment. Collectively, this binary synergistic elastomeric patch offers a simple and universal strategy for treating refractory oral mucosal lesions represented by oral leukoplakia.

口腔白斑(OLK)是一种常见的口腔潜在恶性疾病。针对OLK的核心发病机制,我们将硫辛酸与fda批准的抗菌药物月牙酰精氨酸乙酯盐酸盐结合,通过一步溶剂蒸发策略开发了一种基于聚硫辛酸的生物胶粘剂弹性贴片。在这个二元体系中,LAE自组装成纳米胶束,向外辐射的胍基充当“多臂抓手”,通过多个氢键和与羧基的静电相互作用抑制室温下PolyLA的解聚。弹性体表面丰富的羧基提供了适合动态口腔环境的优异的湿组织粘附性。进一步应用具有不同端基的表面活性剂来验证这种二元设计策略的通用性,并阐明分子间相互作用强度对材料稳定性、结晶度和力学性能的调节作用。体外生物学评价表明,PolyLA/LAE贴片能够有效清除ROS,抑制白色念珠菌增殖,诱导口腔角化异常细胞凋亡,同时保持良好的生物相容性。在大鼠OLK模型中,该贴片显示出令人满意的治疗效果,与临床维生素a软膏相当。总的来说,这种二元协同弹性贴片为治疗以口腔白斑为代表的难治性口腔黏膜病变提供了一种简单而通用的策略。
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引用次数: 0
Zeolitic imidazolate frameworks for lung cancer diagnosis and therapy: design principles and biomedical applications. 沸石咪唑盐肺癌诊断和治疗框架:设计原则和生物医学应用。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-07 DOI: 10.1039/d6bm00962j
Tianqing Jiang, Shihai Yin, Shiting Tang, Yanlong Zhou, Pingfang Lu, Alireza Nezamzadeh-Ejhieh, Shaobo Liu, Shreya Srivastava, Abhinav Kumar

Lung cancer remains one of the most prevalent and lethal malignancies worldwide, with its clinical management being hindered by high invasiveness, early metastasis, therapeutic resistance, and the severe adverse effects associated with conventional treatment modalities. Nanoparticle-based formulations have emerged as promising platforms for lung cancer therapy owing to their ability to enhance drug bioavailability and enable targeted, sustained, and controlled drug delivery. Despite these advantages, their broader clinical applications are often limited by insufficient stability, rapid systemic clearance, and suboptimal targeting efficiency in complex physiological environments. In this context, zeolitic imidazolate frameworks (ZIFs), a distinctive subclass of metal-organic frameworks, have attracted considerable attention because of their high surface area, tunable pore structures, excellent loading capacity, biocompatibility, and stimulus-responsive degradation behaviour. These unique features enable the efficient encapsulation of therapeutic and diagnostic agents and facilitate their controlled release within the tumor microenvironment, thereby improving treatment specificity and reducing off-target effects. This review discusses the fundamental design principles, synthesis strategies, structural characteristics, and functionalization approaches of ZIF-based materials, with particular emphasis on their emerging applications in lung cancer diagnosis and therapy. Recent advances in biosensing, bioimaging, drug delivery, chemotherapy, phototherapy, immunotherapy, and multifunctional therapeutic platforms are critically examined, together with the interactions of ZIF-based systems with the tumor microenvironment. The review further highlights the growing role of artificial intelligence in the screening, design, and optimization of ZIF materials and discusses the major challenges associated with their clinical translation. Collectively, these advances underscore the considerable potential of ZIF-based platforms in developing more effective and safer strategies for lung cancer diagnosis and therapy.

肺癌仍然是世界范围内最常见和最致命的恶性肿瘤之一,其临床管理受到高侵袭性、早期转移、治疗耐药性以及与常规治疗方式相关的严重不良反应的阻碍。基于纳米颗粒的制剂已成为肺癌治疗的有前途的平台,因为它们能够提高药物的生物利用度,并实现靶向、持续和控制的药物递送。尽管有这些优势,但它们的广泛临床应用往往受到稳定性不足、全身清除迅速以及在复杂生理环境中靶向效率不佳的限制。在这种情况下,沸石咪唑盐框架(ZIFs)作为金属有机框架的一个独特亚类,由于其高表面积、可调孔结构、优异的负载能力、生物相容性和刺激响应降解行为而引起了相当大的关注。这些独特的特性使治疗和诊断药物能够有效地包封,并促进其在肿瘤微环境内的控制释放,从而提高治疗特异性,减少脱靶效应。本文综述了zif基材料的基本设计原理、合成策略、结构特点和功能化方法,重点介绍了zif基材料在肺癌诊断和治疗方面的新应用。生物传感、生物成像、药物传递、化疗、光疗、免疫治疗和多功能治疗平台的最新进展,以及基于zif的系统与肿瘤微环境的相互作用。这篇综述进一步强调了人工智能在筛选、设计和优化ZIF材料方面日益增长的作用,并讨论了与临床转化相关的主要挑战。总的来说,这些进展强调了基于zif的平台在开发更有效和更安全的肺癌诊断和治疗策略方面的巨大潜力。
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引用次数: 0
A bilayer nerve conduit integrating aligned guidance with an RGI peptide/retinoic acid-loaded hydrogel for peripheral nerve regeneration. 结合RGI肽/维甲酸负载水凝胶定向引导的双层神经导管用于周围神经再生。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-06 DOI: 10.1039/d6bm01173j
Zhiwei Zhao, Jincheng Li, Jianfeng Liu, Boyuan Liu, Guanhua Yang, Bin Liu

The repair of long-gap peripheral nerve defects remains challenging, as regeneration depends on temporally coordinated bioactive regulation and spatially organized guidance. To address this, we developed a spatiotemporally coordinated nerve conduit integrating an injectable thermosensitive poly(amino acid) hydrogel with an aligned-random bilayer poly(ε-caprolactone) (PCL) wall. A brain-derived neurotrophic factor (BDNF)-mimetic RGI peptide was covalently tethered to mPEG-PMet-PLysMA (P), and retinoic acid (RA) was physically incorporated to form P-RGI@RA. Aligned luminal fibers promoted Schwann cell orientation and spreading, whereas random outer fibers increased transverse tensile strength and elastic modulus by 4.4- and 6.0-fold, respectively, relative to fully aligned membranes. In vitro, the RGI-conjugated formulation increased the mean longest neurite length in PC12 cells, whereas the RA-containing formulation enhanced Schwann cell migration, with the respective responses reaching 1.9- and 1.7-fold the control values. In a 10 mm rat sciatic nerve defect model, P-RGI@RA-filled conduits produced the most favorable repair profile among conduit-treated groups. At 12 weeks, the compound muscle action potential (CMAP) amplitude ratio and injured-to-contralateral gastrocnemius wet weight ratio were 2.3- and 1.5-fold those of hollow conduits, reaching 88% and 92% of the corresponding autograft values, respectively. These outcomes were accompanied by improved axon- and Schwann cell-associated regeneration, myelin ultrastructure, and target muscle preservation. Proteomics associated P-RGI@RA treatment with cytoskeletal regulation, extracellular matrix remodeling, axon guidance, and inflammation-related pathways, while immunoblotting showed increased phosphorylation of phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK). This conduit-hydrogel system provides a potential strategy for peripheral nerve regeneration.

长间隙周围神经缺损的修复仍然具有挑战性,因为再生依赖于时间协调的生物活性调节和空间组织的引导。为了解决这个问题,我们开发了一种时空协调的神经导管,将可注射的热敏聚(氨基酸)水凝胶与排列随机的双层聚(ε-己内酯)(PCL)壁结合在一起。将脑源性神经营养因子(BDNF)模拟RGI肽共价连接到mPEG-PMet-PLysMA (P)上,并将视黄酸(RA)物理结合形成P-RGI@RA。与完全排列的膜相比,排列整齐的内腔纤维促进了雪旺细胞的定向和扩散,而随机排列的外纤维使横向拉伸强度和弹性模量分别提高了4.4倍和6.0倍。在体外,rgi结合制剂增加了PC12细胞的平均最长神经突长度,而含有ra的制剂增强了雪旺细胞的迁移,分别达到对照值的1.9倍和1.7倍。在10mm大鼠坐骨神经缺损模型中,P-RGI@RA-filled导管在导管治疗组中产生了最有利的修复效果。12周时,复合肌动作电位(CMAP)振幅比和损伤对侧腓肠肌湿重比分别是空心导管的2.3倍和1.5倍,分别达到自体移植物值的88%和92%。这些结果伴随着轴突和雪旺细胞相关再生、髓鞘超微结构和靶肌肉保存的改善。蛋白质组学将P-RGI@RA治疗与细胞骨架调节、细胞外基质重塑、轴突引导和炎症相关途径相关,而免疫印迹显示磷酸化肌肽3-激酶/蛋白激酶B (PI3K/AKT)和丝裂原活化蛋白激酶/细胞外信号调节激酶(MEK/ERK)磷酸化增加。这种导管-水凝胶系统为周围神经再生提供了一种潜在的策略。
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引用次数: 0
Mannose-targeted iguratimod liposomes in an HA-derived hydrogel: a synergistic therapy for rheumatoid arthritis via macrophage targeting and ROS scavenging. 甘露糖靶向iguratimod脂体中的ha衍生水凝胶:通过巨噬细胞靶向和ROS清除来协同治疗类风湿关节炎。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-06 DOI: 10.1039/d6bm00740f
Jun Wei, Yiqun Wu, Yumei Chen, Yangjingwan He, Faisal Raza, Hajra Zafar, Ting Wang, Tianli Tian, Liang Ge, Yunkai Wu, Chunli Zheng

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible joint damage. Iguratimod (IGU), a novel small-molecule disease-modifying antirheumatic drug (DMARD), is limited by low solubility, inadequate joint accumulation and hepatotoxicity when administered orally. To address these limitations, we developed an injectable composite hydrogel (IGU-Man-Lip@Vc-HA) by incorporating mannose-modified IGU liposomes (IGU-Man-Lip) into a vitamin C-functionalized hyaluronic acid (Vc-HA) matrix with ROS-scavenging activity. In this system, IGU-Man-Lip overcame the poor solubility of iguratimod and actively targeted synovial macrophages via overexpressed mannose receptors (MR), thereby downregulating inflammatory cytokine levels and exerting bone-protective effects. Concurrently, the Vc-HA hydrogel scavenged ROS to remodel the inflammatory microenvironment. Furthermore, the resistance of Vc-HA to degradation significantly prolonged intra-articular retention, thereby enhancing drug accumulation in joints. This hybrid delivery system exhibited favorable biocompatibility, as well as potent anti-inflammatory and bone-protective efficacy. In collagen-induced arthritis (CIA) rats, intra-articular injections achieved significant joint enrichment, potent anti-inflammatory activity and articular repair without detectable systemic toxicity. This multifunctional composite system constitutes a synergistic RA therapeutic strategy by concurrently addressing targeted drug delivery and oxidative stress to improve anti-inflammatory efficacy along with bone protective effects, providing a promising RA-specific treatment approach.

类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其特征是持续的滑膜炎症和不可逆的关节损伤。Iguratimod (IGU)是一种新型小分子疾病改善抗风湿药物(DMARD),口服给药时存在溶解度低、关节蓄积不足和肝毒性的限制。为了解决这些局限性,我们开发了一种可注射的复合水凝胶(IGU-Man-Lip@Vc-HA),将甘露糖修饰的IGU脂质体(IGU- man - lip)结合到具有ros清除活性的维生素c功能化透明质酸(Vc-HA)基质中。在该系统中,IGU-Man-Lip通过过表达甘露糖受体(MR)克服iguratimod的溶解度差,主动靶向滑膜巨噬细胞,从而下调炎症细胞因子水平,发挥骨保护作用。同时,Vc-HA水凝胶清除ROS,重塑炎症微环境。此外,Vc-HA对降解的抵抗显著延长了关节内潴留,从而增强了关节内药物的蓄积。该混合给药系统表现出良好的生物相容性,以及有效的抗炎和骨保护功效。在胶原诱导关节炎(CIA)大鼠中,关节内注射获得了显著的关节富集、有效的抗炎活性和关节修复,而没有可检测到的全身毒性。这种多功能复合系统通过同时解决靶向药物传递和氧化应激,提高抗炎疗效和骨骼保护作用,构成了一种协同治疗RA的策略,提供了一种有希望的RA特异性治疗方法。
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引用次数: 0
Impact of the physico-chemical properties of surface-initiated polymer brushes on siRNA binding and transfection efficiency. 表面引发聚合物刷的理化性质对siRNA结合和转染效率的影响。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-06 DOI: 10.1039/d6bm00813e
Carlos E Neri-Cruz, Davide Carta, Julien E Gautrot

Rational design of polycationic gene delivery vectors requires understanding how polymer chemistry governs RNA complexation, cellular uptake, and intracellular release kinetics. Poly(dimethylaminoethyl methacrylate) brushes were found to display striking potential for the delivery of siRNA, with high knockdown efficiency and low cytotoxicity. However, the impact of the physico-chemistry of a broader range of polymer brushes on RNA delivery has not been explored. Using a library of 10 cationic polymer brushes spanning tertiary amine and quaternary ammonium chemistries, we reveal how hydrophobicity, pKa, rigidity, and quaternisation modulate siRNA delivery and gene silencing. Combining ellipsometry and surface plasmon resonance, we find that RNA binding capacity correlates directly with pH-responsiveness and the chain rigidity of brushes. Quaternisation with short methyl groups fundamentally altered binding mechanisms, eliminating pH sensitivity while improving colloidal stability and reducing cytotoxicity. To investigate the impact of the physico-chemical properties on transfection efficiency, the uptake of brush-RNA complexes was examined by confocal microscopy and flow cytometry and we quantified cytosolic release using a competitive binding microscopic assay. We observe excellent correlation between the impact of the brush physico-chemistry on release kinetics and long term silencing efficiency. Remarkably, we report that the binding capacity of RNA within brushes does not always correlate with cellular internalisation, competitive desorption and transfection efficiency: rigid imidazole brushes achieved robust gene silencing despite binding substantially less RNA than poly(alkylamine methacrylate) brushes. These findings expand the delivery vector design space, enabling the rational engineering of next-generation polymeric carriers for controlled RNA delivery kinetics.

合理设计多阳离子基因传递载体需要了解聚合物化学如何控制RNA络合,细胞摄取和细胞内释放动力学。聚(二甲氨基乙基甲基丙烯酸酯)刷被发现具有惊人的siRNA递送潜力,具有高敲低效率和低细胞毒性。然而,更广泛的聚合物刷对RNA递送的物理化学影响尚未被探索。使用10个阳离子聚合物刷库跨越叔胺和季铵化学,我们揭示了疏水性,pKa,刚性和季铵化如何调节siRNA传递和基因沉默。结合椭圆偏振和表面等离子体共振,我们发现RNA结合能力与ph响应性和刷链刚性直接相关。短甲基季铵化从根本上改变了结合机制,消除了pH敏感性,同时提高了胶体稳定性并降低了细胞毒性。为了研究物理化学性质对转染效率的影响,我们使用共聚焦显微镜和流式细胞术检测了刷状rna复合物的摄取,并使用竞争性结合显微镜测定了细胞质释放。我们观察到电刷物理化学对释放动力学的影响与长期沉默效率之间存在良好的相关性。值得注意的是,我们报告说,刷内RNA的结合能力并不总是与细胞内化、竞争性解吸和转染效率相关:刚性咪唑刷实现了强大的基因沉默,尽管结合的RNA比聚甲基丙烯酸烷基胺刷少得多。这些发现扩大了传递载体的设计空间,使下一代聚合物载体的合理工程控制RNA传递动力学成为可能。
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引用次数: 0
Matrix stiffness and stress relaxation regulate matrix-bound nanovesicle release from alginate hydrogels. 基质刚度和应力松弛调节海藻酸盐水凝胶中基质结合的纳米囊泡释放。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-10-03 DOI: 10.1039/d6bm00832a
Renata Dos Reis Marques, Jane A Baude, Gianna M Gathman, Ava I Salami, Ryan S Stowers, Marley J Dewey

Matrix-bound nanovesicles (MBVs) are a recently discovered subclass of small extracellular vesicles (EVs) that reside within the extracellular matrix of non-mineralized tissues throughout the body. Functionally, MBVs exhibit unique immunomodulatory properties that have been leveraged therapeutically to treat various tissue pathologies, including periprosthetic osteolysis, rheumatoid arthritis, and skeletal muscle injury. However, like other EVs, the therapeutic efficacy of MBV applications is limited by delivery methods, namely bolus injections, that offer poor control of EV persistence and bioavailability at the site of administration. We hypothesized that a superior MBV delivery platform could be developed by entrapping MBVs in a tunable, engineered alginate matrix to control retention and release of MBVs on therapeutically relevant timescales. To this end, we encapsulated dermal fibroblast MBVs in bioinert alginate hydrogels with varying stiffness and stress relaxation rates to determine the impact of matrix mechanical properties on MBV release and retention over a 14-day period. We found that stiffer matrices increased MBV release and decreased MBV retention compared to their softer counterparts. Additionally, fast-relaxing matrices retained fewer MBVs than slow-relaxing matrices regardless of differences in matrix stiffness. We then compared our results to synthetic liposomes and found these results mirror our MBV results, demonstrating that alginate materials may be utilized for more precise control of EV and liposome delivery in the body and may overcome limitations associated with current EV administration methods.

基质结合纳米囊泡(mbv)是最近发现的小细胞外囊泡(ev)亚类,存在于全身非矿化组织的细胞外基质中。在功能上,mbv表现出独特的免疫调节特性,已被用于治疗各种组织病理,包括假体周围溶骨、类风湿关节炎和骨骼肌损伤。然而,与其他EV一样,MBV应用的治疗效果受到递送方法(即大剂量注射)的限制,这种方法对EV的持久性和给药部位的生物利用度控制较差。我们假设,通过将MBV包裹在可调节的工程海藻酸盐基质中,以控制MBV在治疗相关时间尺度上的保留和释放,可以开发出一种优越的MBV递送平台。为此,我们将真皮成纤维细胞MBV包封在具有不同刚度和应力松弛率的生物惰性海藻酸盐水凝胶中,以确定基质力学性能对MBV释放和保留的影响,为期14天。我们发现,与较软的基质相比,较硬的基质增加了MBV的释放,减少了MBV的保留。此外,无论矩阵刚度的差异如何,快松弛矩阵比慢松弛矩阵保留更少的mbv。然后,我们将我们的结果与合成脂质体进行了比较,发现这些结果反映了我们的MBV结果,表明海藻酸盐材料可用于更精确地控制EV和脂质体在体内的传递,并可能克服当前EV给药方法相关的局限性。
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Biomaterials Science
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