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Charge-based supramolecular peptide nanocomplexes for oral delivery via transporter-driven endocytosis 通过转运蛋白驱动的内吞作用口服递送的基于电荷的超分子肽纳米复合物
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123903
So-Hyeon Park , Gaeun Ma , Seong Jin Park , Seong-Bin Yang , Minho Seo , Jun-Hyuck Lee , Seho Kweon , Jooho Park
The development of charge-based self-assembled supramolecules can provide a groundbreaking advancement in the oral delivery of nanoparticles. In this study, we developed a series of positively charged peptide-engineered bile acids (PCBs) for the first time to interact with the negatively charged semaglutide (SG), a widely used Glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of obesity and diabetes. Among the synthesized PCBs, PCB4 self-assembled with semaglutide via electrostatic interactions to form stable supramolecular nanoparticles, termed positively charged bile acid-saturated semaglutide (PBSG) nanocomplexes, with an average size of approximately 279 nm under aqueous conditions. These PBSG nanocomplexes demonstrated enhanced permeability and absorption through bile acid transporter-driven endocytosis in intestinal cells and tissues, inducing natural breakdown of cell membranes. Notably, PBSG nanocomplex increased the gastrointestinal (GI) permeation and oral absorption of semaglutide, improved therapeutic efficacy in a high-fat diet (HFD)-induced animal model, and inhibited bile acid transporter activity. Moreover, Oral PBSG nanocomplex treatment elevated GLP-1 expression in vivo by facilitating semaglutide delivery and modulating bile acid metabolism at the same time. The development of these novel, charge-based, self-assembling oral peptide nanocomplexes, leveraging positively charged bile acids and transporter-driven uptake, represents a significant advancement in oral nanoparticle delivery and the design of therapeutic nanomaterials.
基于电荷的自组装超分子的发展可以为口服递送纳米颗粒提供突破性的进展。在这项研究中,我们首次开发了一系列带正电荷的肽工程胆汁酸(PCBs)与带负电荷的semaglutide (SG)相互作用,semaglutide (SG)是一种广泛使用的胰高血糖素样肽-1 (GLP-1)受体激动剂,用于治疗肥胖和糖尿病。在合成的多氯联苯中,PCB4通过静电相互作用与半马鲁肽自组装形成稳定的超分子纳米颗粒,称为带正电胆汁酸饱和半马鲁肽(PBSG)纳米复合物,在水条件下平均尺寸约为279 nm。这些PBSG纳米复合物通过胆汁酸转运蛋白驱动的肠细胞和组织内吞作用,诱导细胞膜的自然分解,显示出增强的渗透性和吸收。值得注意的是,PBSG纳米复合物增加了semaglutide的胃肠道(GI)渗透和口服吸收,提高了高脂肪饮食(HFD)诱导的动物模型的治疗效果,并抑制了胆汁酸转运蛋白的活性。此外,口服PBSG纳米复合物治疗通过促进semaglutide递送和调节胆汁酸代谢同时提高GLP-1在体内的表达。这些新型的、基于电荷的、自组装的口服肽纳米复合物的开发,利用带正电荷的胆汁酸和转运蛋白驱动的摄取,代表了口服纳米颗粒递送和治疗性纳米材料设计的重大进步。
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引用次数: 0
Bone microenvironments-regulated biomaterials boost osteonecrosis therapy 骨微环境调节生物材料促进骨坏死治疗。
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123921
Hang Dong , Tongtong Zhu , Yirong Sun , Jiazhen Yang , Guangyao Liu , Guoliang Wang , Jianxun Ding
Several pathological mechanisms, including vascular endothelial cell injury, osteocyte apoptosis, and excessive osteoclast activation, drive osteonecrosis. The disease progression is further exacerbated by disrupted bone remodeling, immune system dysregulation, and impaired regeneration capacity of blood vessel and bone. In weight-bearing joints, progressive subchondral bone deterioration often leads to joint collapse, resulting in chronic pain, stiffness, and disability. Early intervention, typically involving core decompression combined with bone grafting, is essential to prevent irreversible joint damage. Due to the limited availability of autologous bone, research has increasingly focused on developing advanced artificial bone substitutes. This review systematically summarizes current biomaterial-based strategies for treating osteonecrosis, emphasizing innovative approaches that enhance vascular regeneration and osteogenesis while simultaneously suppressing osteoclast activity and modulating immune responses. It also provides an overview of osteogenic biomaterial fabrication and the mechanisms by which biomaterials mediate tissue regeneration, emerging trends in bioactive material development, and potential strategies for advancing next-generation biomaterials.
几种病理机制,包括血管内皮细胞损伤,骨细胞凋亡和过度的破骨细胞活化,驱动骨坏死。骨重塑中断、免疫系统失调、血管和骨骼再生能力受损会进一步加剧疾病进展。在负重关节中,进行性软骨下骨退化常导致关节塌陷,导致慢性疼痛、僵硬和残疾。早期干预,通常包括核心减压联合植骨,对于防止不可逆的关节损伤至关重要。由于自体骨的可用性有限,研究越来越集中于开发先进的人工骨替代品。本文系统总结了目前基于生物材料治疗骨坏死的策略,强调了在抑制破骨细胞活性和调节免疫反应的同时增强血管再生和成骨的创新方法。它还概述了成骨生物材料的制造和生物材料介导组织再生的机制,生物活性材料开发的新趋势,以及推进下一代生物材料的潜在策略。
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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 Pub 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
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 Pub 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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引用次数: 0
Protean bio-heterojunction nanoparticle coating for dynamically modulating diabetic microenvironment 动态调节糖尿病微环境的蛋白质生物异质结纳米颗粒涂层
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-11 DOI: 10.1016/j.biomaterials.2025.123912
Lisha Pan , Ao Zheng , Ning Huang , Shuning Zhang , Lingjie Peng , Fei Zheng , Lingyan Cao , Xiao Wang , Xinquan Jiang
Due to the increased risk of tooth loss associated with diabetes mellitus, patients exhibit a markedly higher demand for dental implant restoration. However, hyperglycemia and the accumulation of advanced glycation end-products (AGEs) induce oxidative stress, increase the risk of peri-implantitis, and impair osseointegration, posing significant challenges to the long-term success of implants. Moreover, the incorporation of antibacterial agents, while enhancing antibacterial efficacy, often elevates oxidative stress and compromises osteogenic capacity and cytocompatibility. Herein, a single-step fabricated bioactive protean TiO2/ZnO bio-heterojunction (BJ) system was developed on carbon-fiber-reinforced polyetheretherketone (CFRPEEK) implants to dynamically modulate diabetic microenvironment through multi-functional synergy (antibacterial/osteogenic/antioxidant). The CFRPEEK was firstly titanium plasma immersion ion implanted (PIIID-Ti) to obtain a micro-nanoscaled titanium dioxide (TiO2) interface. Sequentially, enhanced functionalities were attained by incorporating zinc oxide nanoparticles (ZnO NPs) to form TiO2/ZnO BJ through polydopamine (PDA) assisted π—π covalent immobilization. The results reveal that the TiO2/ZnO BJ effectively modulates reactive oxygen species (ROS) levels. The BJ PIIID-Ti surface exhibits excellent biocompatibility, osteo-inductive potential, and antibacterial efficacy during the early stage, while featuring a ROS scavenging function facilitated by PDA@ZnO NPs during the later stage. In vivo assessments further confirmed that the modified implants possess excellent biosafety, antibacterial ability and osseointegration capacity in the diabetic rat femoral defect model over six weeks. Moreover, the modified implants alleviated oxidative stress and improved the local regenerative microenvironment through activation of the Keap1/Nrf2 pathway. The BJ PIIID-Ti modified CFRPEEK implants demonstrate potential for combating diabetic infection and self-regulating oxidative stress for tissue protection, offering a theoretical basis for future clinical application.
由于糖尿病患者牙齿脱落的风险增加,患者对种植体修复的需求明显增加。然而,高血糖和晚期糖基化终产物(AGEs)的积累会诱导氧化应激,增加种植体周围炎的风险,并损害骨整合,对种植体的长期成功构成重大挑战。此外,抗菌剂的掺入在增强抗菌效果的同时,往往会增加氧化应激,损害成骨能力和细胞相容性。本研究在碳纤维增强聚醚醚酮(CFRPEEK)植入物上制备了一种单步制备的生物活性蛋白TiO2/ZnO生物异质结(BJ)体系,通过抗菌/成骨/抗氧化等多种功能协同作用动态调节糖尿病微环境。首先对CFRPEEK进行钛等离子体浸泡离子注入(piids - ti),获得微纳米级二氧化钛(TiO2)界面。随后,通过聚多巴胺(PDA)辅助π -π共价固定,将氧化锌纳米粒子(ZnO NPs)掺入TiO2/ZnO BJ中,获得了增强的功能。结果表明,TiO2/ZnO BJ能有效调节活性氧(ROS)水平。BJ PIIID-Ti表面在早期表现出良好的生物相容性、骨诱导潜能和抗菌功效,而在后期则具有PDA@ZnO NPs促进的ROS清除功能。体内实验进一步证实,改良后的植入物在糖尿病大鼠股骨缺损模型中具有良好的生物安全性、抗菌能力和骨整合能力。此外,改良后的植入物通过激活Keap1/Nrf2通路,减轻了氧化应激,改善了局部再生微环境。BJ PIIID-Ti改性CFRPEEK植入物具有抗糖尿病感染和自我调节氧化应激保护组织的潜力,为未来临床应用提供了理论基础。
{"title":"Protean bio-heterojunction nanoparticle coating for dynamically modulating diabetic microenvironment","authors":"Lisha Pan ,&nbsp;Ao Zheng ,&nbsp;Ning Huang ,&nbsp;Shuning Zhang ,&nbsp;Lingjie Peng ,&nbsp;Fei Zheng ,&nbsp;Lingyan Cao ,&nbsp;Xiao Wang ,&nbsp;Xinquan Jiang","doi":"10.1016/j.biomaterials.2025.123912","DOIUrl":"10.1016/j.biomaterials.2025.123912","url":null,"abstract":"<div><div>Due to the increased risk of tooth loss associated with diabetes mellitus, patients exhibit a markedly higher demand for dental implant restoration. However, hyperglycemia and the accumulation of advanced glycation end-products (AGEs) induce oxidative stress, increase the risk of peri-implantitis, and impair osseointegration, posing significant challenges to the long-term success of implants. Moreover, the incorporation of antibacterial agents, while enhancing antibacterial efficacy, often elevates oxidative stress and compromises osteogenic capacity and cytocompatibility. Herein, a single-step fabricated bioactive protean TiO<sub>2</sub>/ZnO bio-heterojunction (BJ) system was developed on carbon-fiber-reinforced polyetheretherketone (CFRPEEK) implants to dynamically modulate diabetic microenvironment through multi-functional synergy (antibacterial/osteogenic/antioxidant). The CFRPEEK was firstly titanium plasma immersion ion implanted (PIIID-Ti) to obtain a micro-nanoscaled titanium dioxide (TiO<sub>2</sub>) interface. Sequentially, enhanced functionalities were attained by incorporating zinc oxide nanoparticles (ZnO NPs) to form TiO<sub>2</sub>/ZnO BJ through polydopamine (PDA) assisted π—π covalent immobilization. The results reveal that the TiO<sub>2</sub>/ZnO BJ effectively modulates reactive oxygen species (ROS) levels. The BJ PIIID-Ti surface exhibits excellent biocompatibility, osteo-inductive potential, and antibacterial efficacy during the early stage, while featuring a ROS scavenging function facilitated by PDA@ZnO NPs during the later stage. <em>In vivo</em> assessments further confirmed that the modified implants possess excellent biosafety, antibacterial ability and osseointegration capacity in the diabetic rat femoral defect model over six weeks. Moreover, the modified implants alleviated oxidative stress and improved the local regenerative microenvironment through activation of the Keap1/Nrf2 pathway. The BJ PIIID-Ti modified CFRPEEK implants demonstrate potential for combating diabetic infection and self-regulating oxidative stress for tissue protection, offering a theoretical basis for future clinical application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123912"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Piezoelectric nanomotors for active cartilage regeneration of osteoarthritis via ultrasonic vibration and water splitting 基于超声振动和水裂解的骨关节炎软骨活性再生的压电纳米马达。
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-11 DOI: 10.1016/j.biomaterials.2025.123898
Hong Wang , Cong Xu , Hanfeng Qin , Yalin He , Yunshi Li , Yuejun Jiang , Junbin Gao , Ziwei Hu , Lu Liu , Jiamiao Jiang , Bin Chen , Fei Peng , Yingjia Li , Yingfeng Tu
Osteoarthritis (OA) is a multifactorial joint disorder characterized by articular cartilage degradation and progressive synovial inflammation. The dense and avascular nature of cartilage hinders the delivery efficiency of nanocarriers to their target cells, resulting in limited therapeutic efficacy in clinical trials. Here, we report the design of a Piezo-MnO2 motor for in situ reestablishment of the articular microenvironment by effectively degrading the local excess hydrogen peroxide in the OA microenvironment into oxygen. The generated oxygen ameliorates hypoxic conditions and acts as a propellant for nanomotor actuation, thereby enabling the motor to penetrate deeply into cartilage and synovium. Under mechanical stress induced by ultrasonic vibration, Piezo-MnO2 motors efficiently produced electrical signals via piezoelectric effect. This initiates an influx of extracellular calcium ions, which further upregulates the expression of transforming growth factors and drives cartilage repair. Recognized for its anti-inflammatory and antioxidant properties, the hydrogen produced by ultrasonic piezoelectric effect of the motors significantly diminishes the level of pro-inflammatory cytokines. The developed strategy facilitates rapid in situ cartilage regeneration and articular microenvironment modulation, offering a transformative alternative to conventional OA interventions.
骨关节炎(OA)是一种以关节软骨退化和进行性滑膜炎症为特征的多因素关节疾病。软骨致密和无血管的特性阻碍了纳米载体向靶细胞的递送效率,导致临床试验中的治疗效果有限。在这里,我们报道了一种压电mno2电机的设计,通过有效地将OA微环境中局部过量的过氧化氢降解为氧气,用于原位重建关节微环境。所产生的氧气改善了缺氧条件,并作为纳米运动驱动的推进剂,从而使马达能够深入软骨和滑膜。在超声振动引起的机械应力下,压电马达利用压电效应高效地产生电信号。这引发细胞外钙离子的涌入,进一步上调转化生长因子的表达,推动软骨修复。马达的超声波压电效应产生的氢具有抗炎和抗氧化的特性,可以显著降低促炎细胞因子的水平。开发的策略有助于快速原位软骨再生和关节微环境调节,为传统OA干预提供了一种变革性的替代方案。
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引用次数: 0
Nanomedicine for venous thrombosis: Insights from an inflammatory perspective 纳米药物治疗静脉血栓:从炎症角度的见解。
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-11 DOI: 10.1016/j.biomaterials.2025.123910
Qiu Zeng , Yuan Guo , Anyu Yang , Jun Li
Venous thrombosis (VT), a serious cardiovascular disease, is commonly encountered across various clinical departments. Over the past decade, the negative role of inflammation in the formation and resolution of VT has become increasingly recognized, with numerous inflammation-related mechanisms in VT being revealed. Despite this understanding, traditional antithrombotic treatments for VT primarily focus on targeting coagulation and fibrinolysis, while inadequately addressing inflammation issues. As a result, these treatments face challenges such as limited efficacy and a high risk of bleeding. Against this backdrop, the versatile characteristics of nanomedicine offer promising solutions for treating VT and its accompanying inflammation issues, particularly in preventing premature drug degradation within circulation and facilitating on-demand drug delivery to disease sites. In addition, recent advances in biomimetic nanotechnology and stimuli-responsive systems have further propelled potential applications of nanomedicine in this area. In this context, this review discusses the rational design of nanomaterials, the optimization of targeted delivery approaches, the advancement of stimuli-responsive release strategies, and the integration of biomimetic nanotechnology, all from an inflammation-focused perspective. With these ongoing advancements, nanomedicine holds great promise for precise and comprehensive VT treatment.
静脉血栓形成(VT)是一种严重的心血管疾病,在临床各个科室都很常见。在过去的十年中,炎症在VT的形成和消退中的负面作用越来越被认识到,许多与VT相关的炎症机制被揭示出来。尽管有这样的认识,传统的抗血栓治疗方法主要集中在针对凝血和纤溶,而没有充分解决炎症问题。因此,这些治疗方法面临着诸如疗效有限和出血风险高等挑战。在此背景下,纳米医学的多用途特性为治疗室速及其伴随的炎症问题提供了有希望的解决方案,特别是在防止循环内药物过早降解和促进按需给药到疾病部位方面。此外,仿生纳米技术和刺激响应系统的最新进展进一步推动了纳米医学在这一领域的潜在应用。在此背景下,本文从炎症聚焦的角度讨论了纳米材料的合理设计,靶向递送方法的优化,刺激响应释放策略的进展以及仿生纳米技术的整合。随着这些不断的进步,纳米医学在精确和全面的VT治疗方面具有很大的前景。
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引用次数: 0
A biomaterial implant model demonstrates that immature neutrophils drive immunopathology following acute injury 生物材料植入模型表明,未成熟的中性粒细胞驱动急性损伤后的免疫病理。
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-11 DOI: 10.1016/j.biomaterials.2025.123907
Vinod Kumar Dorai , Alakesh Alakesh , Ranjitha Guttapadu , Shruthi Ksheera Sagar , Meghna Ravishankar Valakatte , Jayashree Vijaya Raghavan , Monisha Mohandas , Kalpana S R , Nagasuma Chandra , Siddharth Jhunjhunwala
Individuals with underlying chronic inflammatory conditions are prone to increased morbidity when posed with an additional inflammatory challenge such as an injury or infection. Numerous components of the immune system including immature neutrophils are thought to contribute to the increased morbidity, but ascribing causation remains challenging due to lack of preclinical models to test the contribution of individual components. Herein, we address this challenge by developing and using a mouse model of biomaterial (chitosan-microspheres) implantation, which results in a specific and pronounced expansion of circulating immature neutrophils that exhibit dysregulated effector functions as determined by single cell RNA sequencing and ex vivo functional assays. Next, in this chitosan-implant model, we pose a second inflammatory challenge involving acute lung injury and demonstrate that the immature neutrophils drive an increase in lung immunopathology. Blocking the migration of these immature neutrophils through the administration of therapeutic antibodies or their function using specific small molecule inhibitors, profoundly lowers the immunopathology caused by the inflammatory challenge. Together, these studies demonstrate the utility of a biomaterial-implant model to establish a causal link between immature neutrophils and increased immunopathology and provides insights into new therapeutic strategies for treating individuals with chronic inflammatory ailments.
患有潜在慢性炎症的个体在受到额外的炎症挑战(如损伤或感染)时,发病率容易增加。免疫系统的许多组成部分,包括未成熟的中性粒细胞,被认为是导致发病率增加的原因,但由于缺乏临床前模型来测试单个组成部分的贡献,确定原因仍然具有挑战性。在此,我们通过开发和使用生物材料(壳聚糖微球)植入的小鼠模型来解决这一挑战,通过单细胞RNA测序和离体功能测定,该模型导致循环中未成熟中性粒细胞特异性和明显的扩增,表现出失调的效应功能。接下来,在这个壳聚糖植入模型中,我们提出了涉及急性肺损伤的第二次炎症挑战,并证明未成熟中性粒细胞驱动肺免疫病理的增加。通过给予治疗性抗体或使用特异性小分子抑制剂来阻断这些未成熟中性粒细胞的迁移,可以大大降低炎症引起的免疫病理。总之,这些研究证明了生物材料植入模型在建立未成熟中性粒细胞与免疫病理增加之间的因果关系方面的实用性,并为治疗慢性炎症性疾病的个体提供了新的治疗策略。
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引用次数: 0
Piezoelectric nanoparticle-driven rhythmic ultrasound neuromodulation for treatment of early-stage Alzheimer's disease 压电纳米颗粒驱动节律超声神经调节治疗早期阿尔茨海默病
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-11 DOI: 10.1016/j.biomaterials.2025.123905
Xiaoxia Li , Sicheng Yan , Mingding Li , Renyuan Liu , Qiangbing Lu , Minghui Lu , Feng Bai , Qun-Dong Shen
Synaptic dysfunction and loss are central drivers of cognitive decline in Alzheimer's disease (AD), yet current therapeutic approaches targeting amyloid-β or tau pathology have largely failed to rescue synaptic function. Neural oscillations and synaptic plasticity are tightly coupled and underpin functional brain networks, suggesting that modulating oscillatory dynamics may offer new therapeutic avenues. Here, we developed a strategy for precise, non-genetic neuromodulation using focused ultrasound and piezoelectric Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) nanoparticles to generate targeted, gamma-frequency electromagnetic fields in the hippocampal CA3 subregion of early-stage AD mouse models. This rhythmic stimulation effectively restored impaired gamma oscillations, enhanced synaptic plasticity, and remodeled memory-related network connectivity, as validated by local field potential recordings, patch-clamp electrophysiology, and functional MRI. Mechanistically, we demonstrate that NF-κB transcription factor activation during rhythmic stimulation regulates AMPAR trafficking by balancing synaptic internalization and delivery, with concurrent upregulation of P300-mediated histone acetylation. Our findings establish a novel paradigm for spatially precise, periodic neuromodulation that restores hippocampal information processing and network function in early AD, highlighting the therapeutic potential of piezoelectric nanomaterials for neural circuit repair in AD and other neurodegenerative diseases characterized by impaired neural rhythms.
突触功能障碍和丧失是阿尔茨海默病(AD)认知能力下降的主要驱动因素,但目前针对淀粉样蛋白-β或tau病理的治疗方法在很大程度上未能挽救突触功能。神经振荡和突触可塑性是紧密耦合的,是大脑功能网络的基础,这表明调节振荡动力学可能提供新的治疗途径。在这里,我们开发了一种精确的非遗传神经调节策略,使用聚焦超声和压电Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT)纳米颗粒在早期AD小鼠模型的海马CA3亚区产生靶向的伽马频率电磁场。经局部场电位记录、膜片钳电生理学和功能性MRI验证,这种有节奏的刺激有效地恢复了受损的伽马振荡,增强了突触可塑性,重塑了记忆相关的网络连接。在机制上,我们证明了NF-κB转录因子在节律性刺激期间的激活通过平衡突触内化和传递来调节AMPAR的运输,同时上调p300介导的组蛋白乙酰化。我们的研究结果为空间精确,周期性神经调节建立了一种新的范例,可以恢复阿尔茨海默病早期海马信息处理和网络功能,突出了压电纳米材料在阿尔茨海默病和其他以神经节律受损为特征的神经退行性疾病的神经回路修复中的治疗潜力。
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引用次数: 0
In situ electrocrosslinkable and immiscible bioadhesive for robust underwater electrophysiological signal interfaces 用于水下电生理信号界面的原位电交联和不混溶生物粘合剂。
IF 12.9 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-11 DOI: 10.1016/j.biomaterials.2025.123904
Hyun Tack Woo , Jinyoung Yun , Jaeyun Lee , Kang-Il Song , Hyung Joon Cha
Effective electrophysiological signal transmission is crucial for tissue regeneration, rehabilitation, and bioelectronic applications, particularly in electrically active tissues such as nerves and muscles. However, existing interface materials face significant limitations, including electrical insulation, instability under physiological conditions due to poor underwater adhesiveness, and incompatibility with irregular tissue surfaces. To address these issues, we propose a conductive bioglue (CBG) comprising hyaluronic acid (HA)-coated eutectic gallium indium (EGaIn) nanodroplets with bioengineered mussel adhesive protein (MAP). This water-immiscible liquid-state CBG undergoes in situ crosslinking electrically, exhibiting excellent adhesion to underwater tissue and metal surfaces, suitable mechanical properties, and robust electrical conductivity. In vivo evaluations demonstrated its ability to restore acute and sustained tissue function while enhancing bioelectronic interfacing. These findings underscore the potential of CBG as a promising biocompatible conductive adhesive interface material for efficient in vivo transmission of electrophysiological signals, offering transformative applications in tissue engineering and bioelectronic devices.
有效的电生理信号传输对于组织再生、康复和生物电子应用至关重要,特别是在神经和肌肉等电活性组织中。然而,现有的界面材料面临着很大的局限性,包括电绝缘、水下粘附性差导致生理条件下的不稳定性以及与不规则组织表面的不相容性。为了解决这些问题,我们提出了一种导电生物胶(CBG),它由透明质酸(HA)包被的共晶镓铟(EGaIn)纳米液滴和生物工程贻贝粘附蛋白(MAP)组成。这种不与水混溶的液态CBG通过电原位交联,对水下组织和金属表面具有优异的附着力,具有合适的机械性能和强大的导电性。在体内的评估表明,它能够恢复急性和持续的组织功能,同时增强生物电子界面。这些发现强调了CBG作为一种有前途的生物相容性导电粘合界面材料的潜力,可以有效地在体内传输电生理信号,在组织工程和生物电子设备中提供变革性的应用。
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引用次数: 0
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