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Development of novel carbon‐based biomedical platforms for intervention in xenotoxicant‐induced Parkinson's disease onset 开发新型碳基生物医学平台,用于干预异毒素诱发的帕金森病发病
Pub Date : 2024-01-27 DOI: 10.1002/bmm2.12072
Jyotish Kumar, Armando Varela‐Ramirez, Mahesh Narayan
Chronic exposure to herbicides, weedicides, and pesticides is associated with the onset and progress of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we have investigated whether quinic‐ and chlorogenic‐acid‐derived Carbon Quantum Dots (QACQDs and ChACQDs, respectively) protect against a (pesticide) paraquat‐insult model of PD. Our results indicated that both types of CQDs intervened in the soluble‐to‐toxic transformation of the amyloid‐forming model protein Hen Egg White Lysozyme (HEWL). Furthermore, QACQDs and ChACQDs demonstrated antioxidant activity while remaining biocompatible in a human neuroblastoma‐derived cell line (SH‐SY5Y) up to 5 mg/ml and protected the cell line from the environmental neurotoxicant (paraquat). Importantly, both CQDs were found to protect dopaminergic neuronal ablation in a paraquat model of Parkinson's disease using the nematode C. elegans. Our results are significant because both plant‐derived organic acids cross the blood–brain barrier, making them attractive for developing CQD architectures. Furthermore, since the synthesis of these CQDs was performed using green chemistry methods from precursor acids that cross the BBB, these engineered bionanomaterial platforms are tantalizing candidates for preventing neurodegenerative disorders associated with exposure to environmental neurotoxicants.
长期接触除草剂、除草剂和杀虫剂与帕金森病(PD)、阿尔茨海默病(AD)和肌萎缩侧索硬化症(ALS)等神经退行性疾病的发生和发展有关。在此,我们研究了源于奎宁酸和绿原酸的碳量子点(分别为 QACQDs 和 ChACQDs)是否能保护(农药)百草枯损伤的帕金森病模型。我们的研究结果表明,这两种类型的碳量子点都能干预淀粉样蛋白母鸡卵白溶菌酶(HEWL)从可溶到有毒的转化过程。此外,QACQDs 和 ChACQDs 在人类神经母细胞瘤衍生细胞系(SH-SY5Y)中表现出抗氧化活性,同时保持生物相容性(最高达 5 毫克/毫升),并保护细胞系免受环境神经毒物(百草枯)的侵害。重要的是,在利用线虫 C. elegans 建立的帕金森病百草枯模型中,我们发现这两种 CQD 都能保护多巴胺能神经元消融。我们的研究结果意义重大,因为这两种源自植物的有机酸都能穿过血脑屏障,使它们对开发 CQD 架构具有吸引力。此外,由于这些 CQDs 是利用绿色化学方法从可穿过 BBB 的前体酸中合成的,因此这些工程仿生材料平台是预防与暴露于环境神经毒物有关的神经退行性疾病的诱人候选材料。
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引用次数: 0
Mucoadhesive and antifouling Janus polysaccharide film for prevention of colorectal cancer recurrence post-surgery 用于预防结肠直肠癌术后复发的黏附性和防污性 Janus 多糖薄膜
Pub Date : 2024-01-22 DOI: 10.1002/bmm2.12071
Jaebeom Lee, Hee Seung Seo, Chun Gwon Park, Mikyung Shin

Colorectal cancer is one of the most common cancers, and current treatment options include surgery, chemotherapy, and radiation therapy. Most patients undergo surgery, which often requires extensive resection of the colon to prevent recurrence and metastasis of residual malignant tumor cells, leading to postoperative pain and discomfort in daily routines. Although versatile therapeutic patches have been developed to induce tumor apoptosis, achieving both great adhesiveness on the mucus layers of the colon tissue and anti-cell/tissue adhesion to other surrounding organs remains a challenge. Herein, we report a Janus polysaccharide film comprising two polymers: mussel-inspired catechol-conjugated chitosan (Chi-C) with muco-adhesiveness, and alginate (Alg) with anti-adhesion property. The Chi-C and Alg polymers form a stably entangled bilayer film via electrostatic interactions. The Janus film shows a strong tissue adhesive strength of ∼10 kPa for the Chi-C layer and weak strength of ∼1 kPa for the Alg layer. Particularly, the Janus film encapsulating an anti-cancer drug exhibits a directional release profile to the tumor site, which is effective for triggering tumor death in in vivo colorectal tumor resection model. Ultimately, such anti-cancer material strategies using bilayered structures are promising for advanced tumor therapy.

大肠癌是最常见的癌症之一,目前的治疗方法包括手术、化疗和放疗。大多数患者都要接受手术治疗,为了防止残留的恶性肿瘤细胞复发和转移,往往需要对结肠进行大范围切除,这就导致了术后疼痛和日常生活中的不适。虽然目前已开发出诱导肿瘤凋亡的多功能治疗贴片,但要同时实现对结肠组织粘液层的高粘附性和对周围其他器官的抗细胞/组织粘附性仍然是一项挑战。在此,我们报告了一种由两种聚合物组成的 Janus 多糖薄膜:具有粘液粘附性的贻贝启发儿茶酚共轭壳聚糖(Chi-C)和具有抗粘附性的海藻酸盐(Alg)。Chi-C 和 Alg 聚合物通过静电作用形成稳定的纠缠双层膜。Janus 膜的 Chi-C 层具有 10 kPa 的强组织粘附强度,而 Alg 层则只有 1 kPa 的弱粘附强度。特别是,封装抗癌药物的 Janus 薄膜显示出向肿瘤部位定向释放的特性,在体内结直肠肿瘤切除模型中可有效引发肿瘤死亡。最终,这种使用双层结构的抗癌材料策略有望用于晚期肿瘤治疗。
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引用次数: 0
Enhancing diaphragmatic defect repair and regeneration: How biomaterials leading the way to progress? 加强膈肌缺损修复和再生:生物材料如何引领进步?
Pub Date : 2024-01-21 DOI: 10.1002/bmm2.12070
Mojtaba Farahani, Przemysław Gnatowski, Raziyeh Najafloo, Tina Navaei, Edyta Piłat, Justyna Kucińska-Lipka, Mohammad Reza Saeb, Masoud Mozafari

Physicians encounter significant challenges in dealing with large diaphragmatic defects in both pediatric and adult populations. Diaphragmatic hernias, such as Morgagni, Bochdalek, and Hiatus hernias, can result in congenital lesions that are often undiagnosed until the appearance of symptoms (bleeding, anemia, and acid reflux). Therefore, substantial potential exists for developing tissue-engineered constructs as novel therapeutic options in clinics. Recent research indicates promising mid-term performance for both natural and synthetic materials. However, studies exploring their application in diaphragm regeneration are limited and remain in the early research stages. Additionally, further investigation is required to address the constraints in human tissue supply for clinical implementation. This article comprehensively reviews the role of biomaterials in diaphragmatic tissue repair and regeneration. It emphasizes biomaterials, including biomimetic polymers used in technological solutions. This summary will enable researchers to critically assess the capability of existing natural biomaterials as essential tissue-engineered patches for clinical use.

医生在处理儿童和成人的巨大膈肌缺损时都会遇到巨大的挑战。膈疝,如 Morgagni、Bochdalek 和 Hiatus 疝,可导致先天性病变,在出现症状(出血、贫血和反酸)之前往往得不到诊断。因此,开发组织工程构建物作为临床新疗法的潜力巨大。最近的研究表明,天然材料和合成材料的中期表现都很不错。然而,探索这些材料在膈肌再生中应用的研究还很有限,仍处于早期研究阶段。此外,还需要进一步调查,以解决临床应用中人体组织供应的限制。本文全面回顾了生物材料在膈肌组织修复和再生中的作用。文章强调了生物材料,包括技术解决方案中使用的仿生物聚合物。这一总结将使研究人员能够批判性地评估现有天然生物材料作为临床使用的重要组织工程补片的能力。
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引用次数: 0
Regulatory mechanisms and regeneration strategies of the soft–hard tissue interface in the human periodontium 人类牙周软硬组织界面的调节机制和再生策略
Pub Date : 2024-01-13 DOI: 10.1002/bmm2.12069
Gao-peng Dang, Yu Wei, Qian-qian Wan, Jun-ting Gu, Kai-yan Wang, Mei-chen Wan, Chen-yu Wang, Jing-han Song, Zhao Mu, Franklin R. Tay, Li-na Niu

The soft-hard tissue interface of the human periodontium is responsible for periodontal homeostasis and is essential for normal oral activities. This soft-hard tissue interface is formed by the direct insertion of fibrous ligaments into the bone tissue. It differs from the unique four-layer structure of the fibrocartilage interface. This interface is formed by a combination of physical, chemical, and biological factors. The physiological functions of this interface are regulated by different signaling pathways. The unique structure of this soft-hard tissue interface has inspired scientists to construct biomimetic gradient structures. These biomimetic systems include nanofiber scaffolds, cell sheets, and hydrogels. Exploring methods to repair this soft-hard tissue interface can help solve clinically unresolved problems. The present review examines the structure of the soft-hard tissue interface of the periodontium and the factors that influence the development of this interface. Relevant regulatory pathways and biomimetic reconstruction methods are also presented to provide ideas for future research on interfacial tissue engineering.

人类牙周的软硬组织界面负责牙周平衡,对正常的口腔活动至关重要。这种软硬组织界面是由纤维韧带直接插入骨组织形成的。它不同于纤维软骨界面的独特四层结构。该界面由物理、化学和生物因素共同作用形成。该界面的生理功能由不同的信号通路调节。这种软硬组织界面的独特结构激发了科学家们构建生物仿生梯度结构的灵感。这些仿生系统包括纳米纤维支架、细胞膜和水凝胶。探索修复这种软硬组织界面的方法有助于解决临床上尚未解决的问题。本综述探讨了牙周软硬组织界面的结构以及影响该界面发展的因素。同时还介绍了相关的调节途径和生物仿生重建方法,为今后的界面组织工程研究提供思路。
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引用次数: 0
Advanced strategies for combinational immunotherapy of cancer based on polymeric nanomedicines 基于聚合物纳米药物的癌症联合免疫疗法的先进策略
Pub Date : 2024-01-12 DOI: 10.1002/bmm2.12067
Kaisheng You, Qi Wang, Mohamed Syazwan Osman, Dongpyo Kim, Qian Li, Chao Feng, Lei Wang, Kuikun Yang

Although immunotherapy has revolutionized cancer therapy by providing efficient tumor growth suppression, long-term protection from recurrence as well as minimized side effects, the low response rate significantly limits the clinical application of immunotherapy in board types of solid tumors. In order to improve the therapeutic efficacy, conventional therapies including radiotherapy, chemotherapy, phototherapy and chemodynamic therapy are employed to combine with immunotherapy to elicit stronger antitumor immune responses. Polymer nanomedicines are frequently utilized in synergistic immunotherapy and other therapies owing to their tunable physiochemical properties, high drug loading capacity, ease of modification and low toxicity. With elaborate design and tailored properties, polymer nanomedicines can significantly enhance antitumor efficacy by enhancing tumor specificity, priming immune cells and amplifying immune responses in tumors. However, until now, there is no review solely dedicated to the comprehensive development of polymer-based platforms for combinational immunotherapy of cancers. Herein, this paper summarizes latest advances in the design, fabrication and application of polymer nanomedicines in combinational immunotherapy and traditional antitumor strategies including radiotherapy, chemotherapy, photothermal therapy, photodynamic therapy and other therapies. An outlook on the trajectory and potential challenges of polymer nanomedicines in bridging the gap between immunotherapy and conventional therapies is also discussed.

尽管免疫疗法能有效抑制肿瘤生长、长期防止复发并将副作用降至最低,从而为癌症治疗带来了革命性的变化,但由于反应率低,大大限制了免疫疗法在各类实体瘤中的临床应用。为了提高疗效,放疗、化疗、光疗和化学动力疗法等传统疗法被用来与免疫疗法相结合,以激发更强的抗肿瘤免疫反应。聚合物纳米药物因其可调整的理化特性、高载药能力、易改性和低毒性,经常被用于协同免疫疗法和其他疗法。通过精心设计和量身定制的特性,聚合物纳米药物可以通过增强肿瘤特异性、激活免疫细胞和扩大肿瘤免疫反应来显著提高抗肿瘤疗效。然而,到目前为止,还没有专门针对基于聚合物的癌症联合免疫疗法平台的全面发展的综述。本文总结了聚合物纳米药物在联合免疫疗法和传统抗肿瘤策略(包括放疗、化疗、光热疗法、光动力疗法和其他疗法)中的设计、制造和应用方面的最新进展。文章还展望了聚合物纳米药物在弥合免疫疗法与传统疗法之间差距方面的发展轨迹和潜在挑战。
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引用次数: 0
Nano-bio interactions between 2D nanomaterials and mononuclear phagocyte system cells 二维纳米材料与单核吞噬系统细胞之间的纳米生物相互作用
Pub Date : 2024-01-10 DOI: 10.1002/bmm2.12066
Jing Zhao, Zheng Chen, Shanbiao Liu, Pin Li, Shiyi Yu, Daishun Ling, Fangyuan Li

Two-dimensional (2D) nanomaterials, known for their unique atomic arrangements and exceptional physicochemical properties, have garnered significant attention in biomedical applications, particularly in the realms of immunotherapy for tissue engineering and tumor therapy. These applications necessitate a thorough assessment of the potential influence of 2D nanomaterials on immune cells. Notably, the mononuclear phagocyte system (MPS) cells, which play pivotal roles in both innate and adaptive immunity, are essential for maintaining organismal homeostasis. MPS cells with phagocytic capability contribute to the prevention of foreign body invasion and the elimination of dead or senescent cells. Furthermore, MPS cells, including macrophages and dendritic cells, serve as vital bridges between innate and adaptive immune responses. Therefore, understanding the nano-bio interactions between 2D nanomaterials and MPS cells is imperative. These nano-bio interactions including cellular uptake, cytocompatibility, and immunological impact are invaluable for the purposeful design of 2D nanomaterials. Herein, we provide an overview of the latest advancements in understanding the nano-bio interactions between 2D nanomaterials and MPS cells, and discuss the current challenges and future prospects of employing 2D nanomaterials in the field of nanomedicine.

二维(2D)纳米材料以其独特的原子排列和优异的物理化学特性而闻名,在生物医学应用领域,尤其是组织工程免疫疗法和肿瘤治疗领域,已引起了广泛关注。这些应用要求对二维纳米材料对免疫细胞的潜在影响进行全面评估。值得注意的是,单核吞噬细胞系统(MPS)细胞在先天性免疫和适应性免疫中发挥着关键作用,是维持机体平衡的关键。具有吞噬能力的 MPS 细胞有助于防止异物入侵和清除死亡或衰老细胞。此外,包括巨噬细胞和树突状细胞在内的 MPS 细胞是先天性免疫反应和适应性免疫反应之间的重要桥梁。因此,了解二维纳米材料与 MPS 细胞之间的纳米生物相互作用势在必行。这些纳米生物相互作用包括细胞吸收、细胞相容性和免疫学影响,对于有针对性地设计二维纳米材料非常宝贵。在此,我们将概述在理解二维纳米材料与 MPS 细胞之间的纳米生物相互作用方面取得的最新进展,并讨论在纳米医学领域使用二维纳米材料的当前挑战和未来前景。
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引用次数: 0
Hexagonal boron nitride nanomaterials for biomedical applications 用于生物医学应用的六方氮化硼纳米材料
Pub Date : 2024-01-03 DOI: 10.1002/bmm2.12068
Congling Wang, Yanyang Long, Yuxian Deng, Yuxin Han, Daria Tishkevich, Minh Ngoc Ha, Qunhong Weng

Hexagonal boron nitride (h-BN) nanomaterials are a rising star in the field of biomedicine. This review presents an overview of the progress in h-BN nanomaterials for biological applications. It begins with a general introduction of the structural characteristics of h-BN, followed by the brief introduction of its physical and chemical properties, including thermal, band and mechanical properties, chemical reactivity, biodegradability and biocompatibility, then emphasizes on the recent progress in the biomedical applications including drug delivery, boron neutron capture therapy (BNCT), bioimaging and nanozyme, and ends with the challenges and perspectives related to the biomedical applications. The advantages of BN nanomaterials used for biomedical applications were analyzed, and their problems were also discussed, inspiring the future rational designs of the BN nanomedicines.

六方氮化硼(h-BN)纳米材料是生物医学领域一颗冉冉升起的新星。本综述概述了 h-BN 纳米材料在生物应用方面的进展。文章首先概括介绍了 h-BN 的结构特征,然后简要介绍了其物理和化学特性,包括热特性、带特性和机械特性、化学反应性、生物降解性和生物相容性,接着重点介绍了药物递送、硼中子俘获疗法(BNCT)、生物成像和纳米酶等生物医学应用的最新进展,最后介绍了生物医学应用面临的挑战和前景。报告分析了硼中子纳米材料在生物医学应用中的优势,并讨论了其存在的问题,对未来硼中子纳米药物的合理设计有所启发。
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引用次数: 0
Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration 将分层二维毡转化为具有定制梯度特征的多相三维纳米纤维支架,用于组织再生
Pub Date : 2023-12-26 DOI: 10.1002/bmm2.12065
S. M. Shatil Shahriar, Navatha Shree Polavoram, Syed Muntazir Andrabi, Yajuan Su, Donghee Lee, Huy Quang Tran, Samantha J. Schindler, Jingwei Xie

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three-dimensional (3D) multiphasic scaffolds using a ‘solids-of-revolution’ inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates that the number of cells migrated and proliferated onto the scaffolds is mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for the promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and high-throughput screening for optimized tissue regeneration.

具有定制梯度特征的多相支架在组织再生应用中大有可为。在此,这项研究报告了利用受 "固体旋转 "启发的气体发泡膨胀技术将二维(2D)分层纤维毡转化为三维(3D)多相支架的过程。这些支架具有精确控制纤维排列、孔隙大小和区域结构的特点。通过操纵纳米纤维垫层和 Pluronic F127 浓度,可以进一步定制不同支架区域内的孔隙大小和纤维排列。细胞对多相支架的反应表明,在支架上迁移和增殖的细胞数量主要取决于孔隙大小而不是纤维排列。多相支架在大鼠体内皮下植入后,发现支架内有大量细胞浸润、新组织形成、胶原沉积和新血管形成,大大超过了传统纳米纤维垫的能力。组织学检查表明,优化孔隙大小和纤维排列对促进细胞浸润和组织再生非常重要。总之,这些支架在组织建模、组织-组织相互作用研究、界面组织工程以及优化组织再生的高通量筛选方面具有潜在的应用前景。
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引用次数: 0
Antigen-specific mRNA lipid nanoparticle platforms for the prevention and treatment of allergy and autoimmune diseases 用于预防和治疗过敏和自身免疫性疾病的抗原特异性 mRNA 脂质纳米粒子平台
Pub Date : 2023-12-14 DOI: 10.1002/bmm2.12060
Emma Y. Yim, Amanda C. Zhou, Yvonne C. Yim, Xiang Wang, Tian Xia

While most nanomedicines primarily aim to stimulate the immune system against infections or tumors, there is a growing demand for inducing immune tolerance under certain conditions, such as allergic and autoimmune diseases. Researchers have explored nanotechnology-based strategies to induce immune tolerance in a targeted and specific manner. One approach involves the use of nanoparticles (NPs) to encapsulate immunosuppressive drugs and/or antigens to educate naïve T cells and promote the generation of antigen-specific regulatory T cells that inhibit immune responses. However, this approach has certain limitations. The hydrophobicity of proteins or peptides restricts the degree to which they can be encapsulated in NPs, which in turn, affects their loading efficiency and treatment efficacy. With the emergence of mRNA lipid nanoparticle (LNP) platforms, there is the possibility of overcoming the limitations of protein and peptide encapsulation. To date, mRNA LNP systems have been shown to provide organ, cellular, and subcellular targeting for the induction of immune tolerance. This method of drug delivery is flexible and scalable that can be customized for a specific patient, resulting in an effective means of administering relevant proteins or epitopes to induce antigen-specific immune tolerance. With continued research and development, this technology could offer a safer and more effective alternative to current therapies, ultimately improving the quality of life of patients worldwide.

虽然大多数纳米药物的主要目的是刺激免疫系统对抗感染或肿瘤,但在某些情况下,如过敏性疾病和自身免疫性疾病,对诱导免疫耐受的需求也在不断增长。研究人员探索了基于纳米技术的策略,以有针对性和特异性的方式诱导免疫耐受。其中一种方法是使用纳米颗粒(NPs)封装免疫抑制药物和/或抗原,以教育幼稚的 T 细胞,促进抑制免疫反应的抗原特异性调节性 T 细胞的生成。然而,这种方法有一定的局限性。蛋白质或肽的疏水性限制了它们被包裹在 NPs 中的程度,进而影响了它们的装载效率和治疗效果。随着 mRNA 脂质纳米粒子(LNP)平台的出现,有可能克服蛋白质和多肽封装的局限性。迄今为止,mRNA LNP 系统已被证明可为诱导免疫耐受提供器官、细胞和亚细胞靶向。这种给药方法具有灵活性和可扩展性,可为特定患者量身定制,从而成为给药相关蛋白质或表位以诱导抗原特异性免疫耐受的有效方法。随着研究和开发的不断深入,这项技术将为现有疗法提供更安全、更有效的替代方案,最终改善全球患者的生活质量。
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引用次数: 0
Advances in Sensor Developments for Cell Culture Monitoring (4/2023) 用于细胞培养监测的传感器开发进展(4/2023)
Pub Date : 2023-12-08 DOI: 10.1002/bmm2.12063
Ka Ram Kim, Woon-Hong Yeo

In article number 10.1002/bmm2.12047, Ka Ram Kim and Woon-Hong Yeo have comprehensively summarized the recent advances in developing various sensors for enhanced monitoring of cellular physiological properties and metabolites with environmental conditions. This image shows the intracellular and extracellular environments that need to be monitored during cell culture processes.

在编号为 10.1002/bmm2.12047 的文章中,Ka Ram Kim 和 Woon-Hong Yeo 全面总结了最近在开发各种传感器以增强对细胞生理特性和代谢物与环境条件的监测方面取得的进展。这张图片显示了细胞培养过程中需要监测的细胞内和细胞外环境。
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引用次数: 0
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