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Corinne E. Packard, 2025 Acta Materialia Silver Medal Award Recipient 科琳-帕卡德(Corinne E. Packard),2025 年《材料学报》银奖获得者
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.07.051
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引用次数: 0
RECIPIENTS OF THE 2023 ACTA MATERIALIA, INC. STUDENT AWARDS Acta Materialia, Inc.学生奖
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.10.001
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引用次数: 0
Stress relaxation behavior of the transition zone in the intervertebral disc 椎间盘过渡区的应力松弛行为。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.09.032
Lydia Vieira , Haim S Mordechai , Mirit Sharabi , Joanne L. Tipper , Javad Tavakoli
The stress relaxation of the TZ region, located at the interface of the Annulus Fibrosus (AF) and Nucleus Pulposus (NP) of the disc, and how its stress is relaxed compared to the adjacent regions is unknown. The current study aimed to identify the TZ stress relaxation properties under different strain magnitudes (0.2, 0.4, and 0.6 mm/mm) and compared the TZ stress relaxation characteristics to the NP and inner AF (IAF) regions at a specific strain magnitude (0.6 mm/mm). The results of the current study revealed that the TZ region exhibited different stress relaxation properties under various strain magnitudes with significantly higher initial (p < 0.008) and reduced stresses (marginally; p = 0.06) at higher strains. Our experimental stress relaxation data revealed a significantly higher equilibrium stress for the IAF compared to the TZ and NP regions (p < 0.001) but not between the TZ and NP regions (p = 0.7). We found that NP radial stress relaxed significantly faster (p < 0.04) than the TZ and NP. Additionally, the current study proposed a simple mathematical model and identified that, consistent with experimental data, the overall effect of region on both the level of decayed stress and the rate at which stress is relaxed was significant (p < 0.006). The current study found a similar stress relaxation characteristic between the NP and TZ regions, while IAF exhibited different stress relaxation properties. It is possible that this mismatch in stress relaxation acts as a shape transformation mechanism triggered by viscoelastic behavior.

Statement of significance

Our understanding of the biomechanical properties of the transition zone (TZ) in the IVD, a region at the interface of the Nucleus Pulposus (NP) and Annulus Fibrosus (AF), is sparse. Unfortunately, there are no current studies that investigate the TZ stress relaxation properties and how stress is relaxed in the TZ compared to the adjacent regions. For the first time, the current study characterized the stress relaxation properties of the TZ and described how the TZ stress is relaxed compared to its adjacent regions.
位于椎间盘纤维环(AF)和髓核(NP)交界处的 TZ 区的应力松弛情况及其与邻近区域相比的应力松弛情况尚不清楚。本研究旨在确定不同应变幅度(0.2、0.4 和 0.6 mm/mm)下 TZ 的应力松弛特性,并比较特定应变幅度(0.6 mm/mm)下 TZ 与 NP 和内 AF(IAF)区域的应力松弛特性。目前的研究结果表明,TZ 区域在不同应变幅度下表现出不同的应力松弛特性,初始应力明显较高(p < 0.008),而在较高应变下应力有所降低(p = 0.06)。我们的应力松弛实验数据显示,与 TZ 和 NP 区域相比,IAF 区域的平衡应力明显更高(p < 0.008)。
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引用次数: 0
Methylglyoxal alters collagen fibril nanostiffness and surface potential 甲基乙二醛改变胶原纤维的纳米硬度和表面电位
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.08.039
Manuel Rufin , Mathis Nalbach , Maja Rakuš , Magdalena Fuchs , Mathias Poik , Georg Schitter , Philipp J. Thurner , Orestis G. Andriotis
Collagen fibrils are fundamental to the mechanical strength and function of biological tissues. However, they are susceptible to changes from non-enzymatic glycation, resulting in the formation of advanced glycation end-products (AGEs) that are not reversible. AGEs accumulate with aging and disease and can adversely impact tissue mechanics and cell-ECM interactions. AGE-crosslinks have been related, on the one hand, to dysregulation of collagen fibril stiffness and damage and, on the other hand, to altered collagen net surface charge as well as impaired cell recognition sites. While prior studies using Kelvin probe force microscopy (KPFM) have shown the effect glycation has on collagen fibril surface potential (i.e., net charge), the combined effect on individual and isolated collagen fibril mechanics, hydration, and surface potential has not been documented. Here, we explore how methylglyoxal (MGO) treatment affects the mechanics and surface potential of individual and isolated collagen fibrils by utilizing atomic force microscopy (AFM) nanoindentation and KPFM. Our results reveal that MGO treatment significantly increases nanostiffness, alters surface potential, and modifies hydration characteristics at the collagen fibril level. These findings underscore the critical impact of AGEs on collagen fibril physicochemical properties, offering insights into pathophysiological mechanical and biochemical alterations with implications for cell mechanotransduction during aging and in diabetes.

Statement of significance

Collagen fibrils are susceptible to glycation, the irreversible reaction of amino acids with sugars. Glycation affects the mechanical properties and surface chemistry of collagen fibrils with adverse alterations in biological tissue mechanics and cell-ECM interactions. Current research on glycation, at the level of individual collagen fibrils, is sparse and has focused either on collagen fibril mechanics, with contradicting evidence, or surface potential. Here, we utilized a multimodal approach combining Kelvin probe force (KPFM) and atomic force microscopy (AFM) to examine how methylglyoxal glycation induces structural, mechanical, and surface potential changes on the same individual and isolated collagen fibrils. This approach helps inform structure-function relationships at the level of individual collagen fibrils.
胶原纤维是生物组织机械强度和功能的基础。然而,胶原纤维易受非酶糖化的影响而发生变化,形成不可逆转的高级糖化终产物(AGEs)。AGEs 会随着衰老和疾病的发生而累积,并对组织力学和细胞与细胞间的相互作用产生不利影响。AGE 交联一方面与胶原纤维硬度和损伤失调有关,另一方面也与胶原蛋白净表面电荷改变以及细胞识别位点受损有关。虽然之前使用开尔文探针力显微镜(KPFM)进行的研究显示了糖化对胶原纤维表面电位(即净电荷)的影响,但对单个和孤立胶原纤维力学、水合作用和表面电位的综合影响还没有记录。在这里,我们利用原子力显微镜(AFM)纳米压痕法和 KPFM 探索了甲基乙二醛(MGO)处理如何影响单个和分离胶原纤维的力学和表面电位。我们的研究结果表明,MGO 处理会显著增加纳米硬度、改变表面电位并改变胶原纤维水平的水合特性。这些发现强调了 AGEs 对胶原纤维理化特性的关键影响,为病理生理机械和生化改变提供了见解,对衰老过程中和糖尿病患者的细胞机械传导产生了影响。意义说明:胶原纤维易发生糖化,即氨基酸与糖发生不可逆的反应。糖化会影响胶原纤维的机械性能和表面化学性质,从而对生物组织的机械性能和细胞与细胞间的相互作用产生不利影响。目前有关单个胶原纤维糖化的研究很少,主要集中在胶原纤维力学(证据相互矛盾)或表面电位方面。在这里,我们采用了一种结合开尔文探针力(KPFM)和原子力显微镜(AFM)的多模态方法,来研究甲基乙二醛糖化如何在相同的单个和分离胶原纤维上诱导结构、机械和表面电位变化。这种方法有助于了解单个胶原纤维水平上的结构-功能关系。
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引用次数: 0
Visceral pleura mechanics: Characterization of human, pig, and rat lung material properties 内脏胸膜力学:内脏胸膜力学:人、猪和大鼠肺材料特性的表征
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.09.003
Gustavo O. Ramirez , Crystal A. Mariano , David Carter , Mona Eskandari
Pulmonary air leaks are amongst the most common complications in lung surgery. Lung sealants are applied to the organ surface and need to synchronously stretch with the visceral pleura, the layer of tissue which encompasses the lung parenchymal tissue. These adhesives are commonly tested on pig and rat lungs, but applied to human lungs. However, the unknown mechanics of human lung visceral pleura undermines the clinical translatability of such animal-tested sealants and the absence of how pig and rat lung visceral pleura compare to human tissues is necessary to address. Here we quantify the biaxial planar tensile mechanics of visceral pleura from healthy transplant-eligible and smoker human lungs for the first time, and further compare the material behaviors to pig and rat lung visceral pleura. Initial and final stiffness moduli, maximum stress, low-to-high strain transition, and stress relaxation are analyzed and compared between and within groups, further considering regional and directional dependencies. Visceral pleura tissue from all species behave isotropically, and pig and human visceral pleura exhibits regional heterogeneity (i.e. upper versus lower lobe differences). We find that pig visceral pleura exhibits similar initial stiffness moduli and regional trends compared to human visceral pleura, suggesting pig tissue may serve as a viable animal model candidate for lung sealant testing. The outcomes and mechanical characterization of these scarce tissues enables future development of biomimetic lung sealants for improved surgical applications.

Statement of significance

Surgical lung sealants must synchronously deform with the underlying tissue and with each breath to minimize post-operative air leaks, which remain the most frequent complications of pulmonary intervention. These adhesives are often tested on pig and rat lungs, but applied to humans; however, the material properties of human lung visceral pleura were previously unexplored. Here, for the first time, the mechanics of human visceral pleura tissue are investigated, further contrasting rarely acquired donated lungs from healthy and smoking individuals, and additionally, comparing biaxial planar material characterizations to animal models often employed for pulmonary sealant development. This fundamental material characterization addresses key hindrances in the advancement of biomimetic sealants and evaluates the translatability of animal model experiments for clinical applications.
肺漏气是肺部手术中最常见的并发症之一。肺部密封剂应用于器官表面,需要与内脏胸膜同步伸展,内脏胸膜是包裹肺实质组织的一层组织。这些粘合剂通常在猪肺和大鼠肺这两种动物身上进行测试,但却应用于人类肺部。然而,由于人类肺脏胸膜的力学结构尚不清楚,因此此类经动物测试的密封剂无法应用于临床,而猪肺和大鼠肺脏胸膜与人类组织相比的差异也是需要解决的问题。在这里,我们首次量化了符合移植条件的健康人肺和吸烟者肺内脏胸膜的双轴平面拉伸力学,并进一步将其材料行为与猪肺和大鼠肺内脏胸膜进行了比较。分析和比较了组间和组内的初始和最终刚度模量、最大应力、低应变到高应变的转变以及应力松弛,并进一步考虑了区域和方向依赖性。所有物种的内脏胸膜组织都表现为各向同性,猪和人的内脏胸膜表现出区域异质性(即上叶与下叶的差异)。我们发现,与人类内脏胸膜相比,猪内脏胸膜表现出相似的初始刚度模量和区域趋势,这表明猪组织可作为肺密封剂测试的可行候选动物模型。这些稀缺组织的结果和力学特征有助于未来仿生肺密封剂的开发,以改进外科应用。意义声明:手术用肺密封剂必须与下层组织同步变形,并随着每次呼吸而变形,以最大限度地减少术后漏气,而漏气仍是肺部介入手术最常见的并发症。这些粘合剂通常在猪肺和大鼠肺上进行测试,但并不适用于人类;然而,人类肺脏胸膜的材料特性之前尚未得到研究。本文首次研究了人体内脏胸膜组织的力学特性,进一步对比了很少获得的健康人和吸烟者的捐赠肺,并将双轴平面材料特性与肺密封剂开发中经常使用的动物模型进行了比较。这种基本的材料表征解决了生物仿生密封剂发展过程中的主要障碍,并评估了动物模型实验在临床应用中的可转化性。
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引用次数: 0
Near-infrared remote triggering of bio-enzyme activation to control intestinal colonization by orally administered microorganisms 近红外远程触发生物酶激活,控制口服微生物的肠道定植。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.09.044
Wei Sun , Fu Yun , Qinglu Guo , Hao-Lin Guo , Bowen Li , Guoqing Feng , Jimin Cao , Yang Bai , Bin Zheng , Xianhui Ruan
Oral biotherapeutics hold significant promise, but their lack of controllability and targeting poses a major challenge, particularly for intestinal bacterial biotherapeutics. In response, we have developed a nanoencapsulation approach that responds to the release of enzyme activity in the organism and activates the enzyme in situ, allowing for controlled colonization of microbes in the gut. The nano-coating comprises a two-layer structure: an inner layer of polydopamine with photothermal and adhesive properties, and an outer layer of gelatin–sodium carboxymethylcellulose, which is hydrolyzed by cellulases in the gut following photothermal interaction with dopamine. We have successfully achieved controlled colonization of a wide range of microorganisms. Furthermore, in a diabetes model, this approach has had a profound impact on regulating glucagon-like peptide-1 (GLP-1) production, β-cell physiology, and promoting insulin secretion. This nanocoating is achieved by in situ activation of cellulase without the need for genetic or targeted molecular modification, representing a new paradigm and alternative strategy for microbial therapy. It not only enables precise and controlled colonization of probiotics but also demonstrates great potential for broader application in the field of oral biotherapy.

Statement of significance

We have developed a nano-encapsulation method that triggers enzyme activity in response to enzymatic activity, resulting in the controlled release and adhesion of a wide range of microorganisms in the gut. The nano coating comprises two layers: an inner layer of polydopamine with photothermal and adhesion properties, and an outer layer of a gelatin-sodium carboxymethylcellulose polymer, which can be hydrolyzed by cellulases in the intestine. Additionally, this method allows for the preparation of various microbial coatings. This approach holds significant promise for regulating GLP-1 production, the physiological function of pancreatic β-cells, and promoting insulin secretion in diabetes models.
口服生物疗法前景广阔,但其缺乏可控性和靶向性,尤其是对肠道细菌生物疗法而言,是一项重大挑战。为此,我们开发了一种纳米封装方法,它能对生物体内酶活性的释放做出反应,并在原位激活酶,从而实现肠道微生物的可控定植。这种纳米涂层由两层结构组成:内层是具有光热和粘合特性的聚多巴胺,外层是明胶-羧甲基纤维素钠,在与多巴胺发生光热作用后,纤维素酶会在肠道中水解。我们成功实现了多种微生物的可控定植。此外,在糖尿病模型中,这种方法对调节胰高血糖素样肽-1(GLP-1)的产生、β细胞生理机能和促进胰岛素分泌产生了深远影响。这种纳米涂层是通过原位激活纤维素酶实现的,无需进行基因或靶向分子改造,是微生物疗法的一种新模式和替代策略。它不仅实现了益生菌的精确和可控定植,还展示了在口腔生物疗法领域更广泛应用的巨大潜力。意义说明:我们开发了一种纳米封装方法,它能触发酶活性,从而控制肠道内多种微生物的释放和粘附。纳米涂层由两层组成:内层是具有光热和粘附特性的聚多巴胺,外层是明胶-羧甲基纤维素钠聚合物,可在肠道中被纤维素酶水解。此外,这种方法还可以制备各种微生物涂层。这种方法在调节 GLP-1 的产生、胰腺 β 细胞的生理功能以及促进糖尿病模型的胰岛素分泌方面大有可为。
{"title":"Near-infrared remote triggering of bio-enzyme activation to control intestinal colonization by orally administered microorganisms","authors":"Wei Sun ,&nbsp;Fu Yun ,&nbsp;Qinglu Guo ,&nbsp;Hao-Lin Guo ,&nbsp;Bowen Li ,&nbsp;Guoqing Feng ,&nbsp;Jimin Cao ,&nbsp;Yang Bai ,&nbsp;Bin Zheng ,&nbsp;Xianhui Ruan","doi":"10.1016/j.actbio.2024.09.044","DOIUrl":"10.1016/j.actbio.2024.09.044","url":null,"abstract":"<div><div>Oral biotherapeutics hold significant promise, but their lack of controllability and targeting poses a major challenge, particularly for intestinal bacterial biotherapeutics. In response, we have developed a nanoencapsulation approach that responds to the release of enzyme activity in the organism and activates the enzyme in situ, allowing for controlled colonization of microbes in the gut. The nano-coating comprises a two-layer structure: an inner layer of polydopamine with photothermal and adhesive properties, and an outer layer of gelatin–sodium carboxymethylcellulose, which is hydrolyzed by cellulases in the gut following photothermal interaction with dopamine. We have successfully achieved controlled colonization of a wide range of microorganisms. Furthermore, in a diabetes model, this approach has had a profound impact on regulating glucagon-like peptide-1 (GLP-1) production, β-cell physiology, and promoting insulin secretion. This nanocoating is achieved by in situ activation of cellulase without the need for genetic or targeted molecular modification, representing a new paradigm and alternative strategy for microbial therapy. It not only enables precise and controlled colonization of probiotics but also demonstrates great potential for broader application in the field of oral biotherapy.</div></div><div><h3>Statement of significance</h3><div>We have developed a nano-encapsulation method that triggers enzyme activity in response to enzymatic activity, resulting in the controlled release and adhesion of a wide range of microorganisms in the gut. The nano coating comprises two layers: an inner layer of polydopamine with photothermal and adhesion properties, and an outer layer of a gelatin-sodium carboxymethylcellulose polymer, which can be hydrolyzed by cellulases in the intestine. Additionally, this method allows for the preparation of various microbial coatings. This approach holds significant promise for regulating GLP-1 production, the physiological function of pancreatic β-cells, and promoting insulin secretion in diabetes models.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 574-588"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378675","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
Biomimetic copper-containing nanogels for imaging-guided tumor chemo-chemodynamic-immunotherapy 用于成像引导的肿瘤化学-化学动力-免疫疗法的仿生含铜纳米凝胶
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.09.030
Mengsi Zhan , Yao Xu , Liang Jia , Hongwei Yu , Han Wang , Mingwu Shen , Xiangyang Shi
Developing multifunctional nanoplatforms to comprehensively modulate the tumor microenvironment and enhance diagnostic and therapeutic outcomes still remains a great challenge. Here, we report the facile construction of a multivariate nanoplatform based on cancer cell membrane (CM)-encapsulated redox-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) co-loaded with Cu(II) and chemotherapeutic drug toyocamycin (Toy) for magnetic resonance (MR) imaging-guided combination tumor chemodynamic therapy/chemoimmunotherapy. We show that redox-responsive PVCL NGs formed through precipitation polymerization can be aminated, conjugated with 3,4-dihydroxyhydrocinnamic acid for Cu(II) complexation, physically loaded with Toy, and finally camouflaged with CMs. The created ADCT@CM NGs with an average size of 113.0 nm are stable under physiological conditions and can efficiently release Cu(II) and Toy under tumor microenvironment with a high level of glutathione. Meanwhile, the developed NGs are able to enhance cancer cell oxidative stress and endoplasmic reticulum stress by synergizing the effects of chemodynamic therapy mediated by Cu-based Fenton-like reaction and Toy-mediated chemotherapy, thereby triggering significant immunogenic cell death (ICD). In a melanoma mouse model, the NGs show potent immune activation effects to reinforce tumor therapeutic efficacy through ICD induction and immune modulation including high levels of immune cytokine secretion, increased tumor infiltration of CD8+ cytotoxic T cells, and reduced tumor infiltration of regulatory T cells. With the CM coating and Cu(II) loading, the developed NG platform demonstrates homologous tumor targeting and T1-weighted MR imaging, hence providing a general biomimetic NG platform for ICD-facilitated tumor theranostic nanoplatform.

Statement of significance

Developing multifunctional nanoplatforms to comprehensively modulate the tumor microenvironment (TME) and enhance theranostic outcomes remains a challenge. Here, a cancer cell membrane (CM)-camouflaged nanoplatform based on aminated poly(N-vinylcaprolactam) nanogels (NGs) co-loaded with Cu(II) and toyocamycin (Toy) was prepared for magnetic resonance (MR) imaging-guided combination tumor chemodynamic therapy/chemoimmunotherapy. The tumor targeting specificity and efficient TME-triggered release of Cu(II) and Toy could enhance tumor cell oxidative stress and endoplasmic reticulum stress by synergizing the effects of chemodynamic therapy mediated by Cu-based Fenton-like reaction and Toy-mediated chemotherapy, respectively, thereby leading to significant immunogenic cell death (ICD) and immune response. With the CM coating and Cu(II) loading, the developed NG platform also demonstrates good T1-weighted tumor MR imaging performance. Hence, this study provides a general biomimetic NG platform for ICD-facilitated tumor theranostics.
开发多功能纳米平台以全面调节肿瘤微环境并提高诊断和治疗效果仍然是一项巨大挑战。在这里,我们报告了一种基于癌细胞膜(CM)封装的氧化还原响应聚(N-乙烯基己内酰胺)(PVCL)纳米凝胶(NGs)的多元纳米平台的简易构建,该平台共负载了铜(II)和化疗药物玩具霉素(Toy),用于磁共振(MR)成像引导的肿瘤化学动力疗法/血液免疫疗法联合治疗。我们的研究表明,通过沉淀聚合形成的具有氧化还原反应的 PVCL NG 可被胺化,与 3,4-二羟基氢肉桂酸共轭以络合 Cu(II),物理负载 Toy,最后与 CM 伪装在一起。所制备的 ADCT@CM NG 平均尺寸为 113.0 nm,在生理条件下非常稳定,并能在谷胱甘肽含量较高的肿瘤微环境中有效释放 Cu(II) 和 Toy。同时,所开发的 NGs 能够通过协同铜基 Fenton-like 反应介导的化学动力疗法和 Toy 介导的化疗的效果,增强癌细胞氧化应激和内质网应激,从而引发显著的免疫原性细胞死亡(ICD)。在黑色素瘤小鼠模型中,NGs 通过诱导 ICD 和免疫调节(包括高水平的免疫细胞因子分泌、CD8+ 细胞毒性 T 细胞的肿瘤浸润增加以及调节性 T 细胞的肿瘤浸润减少)显示出强大的免疫激活效应,从而加强了肿瘤疗效。在 CM 涂层和 Cu(II) 负载的作用下,所开发的 NG 平台实现了同源肿瘤靶向和 T1 加权 MR 成像,从而为 ICD 促成的肿瘤治疗纳米平台提供了一种通用的生物仿生 NG 平台。意义说明:开发多功能纳米平台以全面调节肿瘤微环境(TME)并提高治疗效果仍然是一项挑战。本文制备了一种基于氨基化聚(N-乙烯基己内酰胺)纳米凝胶(NGs)的癌症细胞膜(CM)伪装纳米平台,该纳米凝胶共同负载了铜(II)和玩具霉素(Toy),可用于磁共振(MR)成像引导的肿瘤化学动力疗法/血液免疫疗法联合疗法。Cu(II)和Toy的肿瘤靶向特异性和高效的TME触发释放可增强肿瘤细胞氧化应激和内质网应激,分别协同Cu基Fenton样反应介导的化学动力疗法和Toy介导的化疗的效果,从而导致显著的免疫原性细胞死亡(ICD)和免疫反应。在 CM 涂层和 Cu(II) 负载的作用下,所开发的 NG 平台还具有良好的 T1 加权肿瘤磁共振成像性能。因此,这项研究为 ICD 促成的肿瘤治疗提供了一种通用的生物仿生 NG 平台。
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引用次数: 0
Fibrinogen αC-region acts as a functional safety latch: Implications for a fibrin biomechanical behaviour model 纤维蛋白原 αC 区域充当功能安全锁:对纤维蛋白生物力学行为模型的影响
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.10.005
Tímea Feller , Helen R. McPherson , Simon D. Connell , Robert A.S. Ariëns
Fibrin has unique biomechanical properties which are essential for its role as a scaffold for blood clots. Fibrin is highly extensible and demonstrates significant strain stiffening behaviour, which is essential for stress-distribution in the network. Yet the exact structures of fibrin at the sub-fibre level that contribute to its unique biomechanical characteristic are unknown. Here we show how truncations of the fibrinogen αC-region impact the biomechanical properties of fibrin fibres. Surprisingly, absence of the complete αC-region did not influence the low strain modulus of fibrin fibres but led to premature fibre rupture and decreased extensibility. Intermediate effects were observed with partial deletion of the αC-region, reflected by intermediate rupture stress and toughness. However, overall strain-stiffening behaviour remained even in absence of the αC-region, indicating that strain stiffening is not due to stress being transferred from the αC-region to the protofibril backbone. Upon stress-relaxation, decay constants and their relative contribution to the total relaxation remained similar at all strains, showing that a distinct relaxation process is present until fibre rupture. However, relative contribution of fast relaxation was maximal only in crosslinked fibres if the flexible αC-connector was present. These data show that the αC-region is not the main load-bearing structure within fibrin fibres and point to a critical role for the protofibril backbone instead. We present a revised structural model based on protofibril branching that fully explains the unique biomechanical behaviour of fibrin fibres, while the αC-region primarily acts as a safety latch at the highest of strains.

Statement of significance

The findings presented in this paper reveal critically important details about how the molecular structure of fibrin contributes to its unique mechanical properties which are essential to fulfil its function as the scaffold of blood clots. In this work we used engineered proteins with alterations in an important but highly disordered area of the molecule called αC-region and we provide direct evidence for the first time for how the absence of either the globular αC-domain, or the complete αC-region impacts the mechanical behaviour of individual fibrin fibres. Using these results we developed a new structural model of protofibril organisation within fibrin fibres that fully explains their strain stiffening, relatively low modulus and their high, largely variable, extensibility.
纤维蛋白具有独特的生物力学特性,这对其作为血凝块支架的作用至关重要。纤维蛋白具有高度延展性,并表现出显著的应变僵化行为,这对网络中的应力分布至关重要。然而,纤维蛋白在亚纤维水平上的确切结构对其独特的生物力学特性的贡献尚不清楚。在这里,我们展示了纤维蛋白原 αC 区域的截断如何影响纤维蛋白纤维的生物力学特性。令人惊讶的是,缺失完整的αC区并不会影响纤维蛋白纤维的低应变模量,但会导致纤维过早断裂并降低延伸性。部分缺失αC区会产生中间效应,表现为中间断裂应力和韧性。然而,即使没有αC区域,整体应变硬化行为仍然存在,这表明应变硬化并不是由于应力从αC区域转移到原纤维骨架。应力松弛时,衰减常数及其对总松弛的相对贡献在所有应变下都保持相似,这表明在纤维断裂之前存在一个独特的松弛过程。然而,只有在存在柔性αC连接体的交联纤维中,快速松弛的相对贡献才最大。这些数据表明,αC 区域并不是纤维蛋白纤维内的主要承载结构,而是原纤维骨架的关键作用。我们提出了一个基于原纤维分支的修正结构模型,该模型可充分解释纤维蛋白纤维的独特生物力学行为,而 αC 区域在最高应变时主要起安全锁扣的作用。意义说明:本文的研究结果揭示了纤维蛋白分子结构如何促成其独特机械特性的重要细节,而这些特性对于实现其作为血凝块支架的功能至关重要。在这项工作中,我们使用了在分子中一个重要但高度无序的区域(称为αC区)发生改变的工程蛋白,并首次提供了直接证据,证明球状αC区或完整αC区的缺失如何影响单个纤维蛋白纤维的机械性能。利用这些结果,我们建立了一个纤维蛋白纤维内原纤维组织的新结构模型,该模型可充分解释纤维蛋白纤维的应变僵化、相对较低的模量及其较高的、在很大程度上可变的延伸性。
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引用次数: 0
Elizabeth Cosgriff-Hernández, 2025 Acta Materialia Mary Fortune Global Diversity Medal Recipient 伊丽莎白-科斯格里夫-埃尔南德斯(Elizabeth Cosgriff-Hernández),2025 年《材料学报》玛丽-财富全球多样性奖章获得者
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.07.047
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引用次数: 0
Polyphenol-modified biomimetic bioadhesives for the therapy of annulus fibrosus defect and nucleus pulposus degeneration after discectomy 用于治疗椎间盘切除术后环状纤维缺损和髓核变性的多酚改性仿生生物粘合剂。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-01 DOI: 10.1016/j.actbio.2024.09.038
Yan Ju , Shiyuan Ma , Meimei Fu , Min Wu , Yue Li , Yue Wang , Meihan Tao , Zhihui Lu , Jinshan Guo
Discectomy is the surgical standard of care to relieve low back pain caused by intervertebral disc (IVD) herniation. However, there remains annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration, which often result in recurrent herniation (re-herniation). Herein, we develop a polyphenol-modified waterborne polyurethane bioadhesives (PPU-glues) to promote therapy prognosis after discectomy. Being composed of tannic acid (TA) mixed cationic waterborne polyurethane nanodispersions (TA/WPU+) and curcumin (Cur) embedded anionic waterborne polyurethane nanodispersions (Cur-WPU-), PPU-glue gels rapidly (<10 s) and exhibits low swelling ratios, tunable degradation rates and good biocompatibility. Due to the application of an adhesion strategy combing English ivy mechanism and particle packing theory, PPU-glue also shows considerable lap shear strength against wet porcine skin (≈58 kPa) and burst pressure (≈26 kPa). The mismatched particle sizes and the opposite charges of TA/WPU+ and Cur-WPU- in PPU-glue bring electrostatic interaction and enhance particle packing density. PPU-glue possesses superior reactive oxygen species (ROS)-scavenging capacity derived from polyphenols. PPU-glue can regulate extracellular matrix (ECM) metabolism in degenerated NP cells, and it can promote therapy biologically and mechanically in degenerated rat caudal discs. In summary, this study highlights the therapeutic approach that combines AF seal and NP augmentation, and PPU-glue holds great application potentials for post discectomy therapy.

Statement of significance

Currently, there is no established method for the therapy of annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration after discectomy. Herein, we developed a polyphenol-modified biomimetic polyurethane bioadhesive (PPU-glue) with strong adhesive strength and superior bioactive property. The adhesion strategy that combined a particle packing theory and an English ivy mechanism was firstly applied to the intervertebral disc repair field, which benefited AF seal. The modified method of incorporating polyphenols was utilized to confer with ROS-scavenging capacity, ECM metabolism regulation ability and anti-inflammatory property, which promoted NP augmentation. Thus, PPU-glue attained the synergy effect for post discectomy therapy, and the design principle could be universally expanded to the bioadhesives for other surgical uses.
椎间盘切除术是缓解椎间盘(IVD)突出引起的腰痛的外科标准疗法。然而,椎间盘纤维环(AF)缺损和髓核(NP)变性仍然存在,这往往会导致椎间盘突出症复发(再疝)。在此,我们开发了一种多酚改性水性聚氨酯生物粘合剂(PPU-胶),以促进椎间盘切除术后的治疗预后。PPU 胶水由单宁酸(TA)混合阳离子水性聚氨酯纳米分散体(TA/WPU+)和姜黄素(Cur)嵌入阴离子水性聚氨酯纳米分散体(Cur-WPU-)组成,能迅速凝胶(PPU-胶水中的+和Cur-WPU-会产生静电作用并提高粒子的堆积密度)。PPU 胶具有源自多酚的卓越的活性氧(ROS)清除能力。PPU-胶能调节变性NP细胞中细胞外基质(ECM)的新陈代谢,并能从生物学和机械学角度促进变性大鼠椎间盘的治疗。总之,本研究强调了将 AF 封闭和 NP 增强相结合的治疗方法,PPU 胶在椎间盘切除术后治疗中具有巨大的应用潜力。意义说明:目前,还没有成熟的方法来治疗椎间盘切除术后纤维环(AF)缺损和髓核(NP)变性。在此,我们开发了一种多酚改性仿生物聚氨酯生物粘合剂(PPU-胶),它具有很强的粘合强度和优异的生物活性。这种结合了颗粒填料理论和英国常春藤机制的粘附策略首先被应用于椎间盘修复领域,使 AF 密封性受益匪浅。改良后的多酚类物质加入方法赋予了 PPU 胶清除 ROS 的能力、调节 ECM 代谢的能力和抗炎特性,从而促进了 NP 的增强。因此,PPU-胶水在椎间盘切除术后治疗中取得了协同效应,其设计原理可普遍推广到其他外科用途的生物粘合剂中。
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引用次数: 0
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Acta Biomaterialia
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