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Engineered microneedles arrays for wound healing 用于伤口愈合的工程微针阵列
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.05.003
Shun Yao, Yuan Luo, Yongan Wang

Wound healing is the regenerative process of original skin structure after destructing by different damage sources. Due to their transdermal delivery capability and high specific surface area, microneedles arrays (MAs) have been recognized as encouraging biomaterials for wound healing. In this review, we have outlined the engineered MAs used for tissue regeneration and wound healing. Engineered MAs were first classified by design methodologies such as bionic design, intelligent-responsive design, actively-triggered design, matrix materials innovation, and composite smart design. Then, the MAs were divided into two categories based on the different loading substances: drug-loaded MAs and living component-loaded MAs. Finally, we have summed up the important elements of the preceding discussions and forecasted their future evolution.

创面愈合是皮肤原始结构受到不同损伤源破坏后的再生过程。由于其透皮递送能力和高比表面积,微针阵列(MAs)已被认为是促进伤口愈合的生物材料。在这篇综述中,我们概述了用于组织再生和伤口愈合的工程化MAs。工程MAs首先按照设计方法进行分类,如仿生设计、智能响应设计、主动触发设计、基质材料创新和复合材料智能设计。然后,根据装载物质的不同,将MAs分为两类:载药MAs和载活组分MAs。最后,我们总结了前面讨论的重要内容,并对其未来的演变进行了预测。
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引用次数: 14
Construction and application of liver cancer models in vitro 肝癌体外模型的构建及应用
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.07.004
Changmin Shao , Qingfei Zhang , Gaizhen Kuang , Qihui Fan , Fangfu Ye

Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide. Although current advances in the treatment of liver cancer, the prognosis of this cancer remains unfavorable. Appropriate liver cancer model in vitro is an important way to study the pathogenesis and drug screening of liver cancer. This review provides a comprehensive summary and discussion on the construction and application of liver cancer models in vitro, in particular hepatocellular carcinoma (HCC). Specifically, after introducing the current methods or techniques for preparing 3D in vitro liver cancer models, this review summarizes the relevant applications of these liver cancer models in vitro, e.g. drug screening, personalized medicine, and other applications. In the end, this review discusses the advantages and disadvantages of the liver cancer models in vitro, and proposes future prospects and research directions.

原发性肝癌是世界上第五大最常见的恶性肿瘤,也是导致癌症死亡的第三大原因。尽管目前肝癌的治疗取得了进展,但这种癌症的预后仍然不利。体外建立合适的肝癌模型是研究肝癌发病机制和药物筛选的重要途径。本文就肝癌体外模型的构建和应用,特别是肝细胞癌(HCC)模型的研究进展进行了综述和讨论。具体而言,本文在介绍了目前体外三维肝癌模型制备方法或技术的基础上,综述了体外三维肝癌模型的相关应用,如药物筛选、个体化治疗等应用。最后,本文综述了体外肝癌模型的优缺点,并提出了未来的展望和研究方向。
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引用次数: 6
Engineered extracellular vesicles: Regulating the crosstalk between the skeleton and immune system 工程细胞外囊泡:调节骨骼和免疫系统之间的串扰
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.06.004
Wei-Wei Yu , Qian-Qian Wan , Yu Wei , Yu-Tao Li , Qi-Hong Li , Tao Ye , Ke-Hui Xu , Jing-Han Song , Chen Lei , Mei-Chen Wan , Kai Jiao , Franklin R Tay , Li-Na Niu

Osteoimmunology has gained momentum in recent years, focusing on the crosstalk between the skeleton and the immune system. Extracellular vesicles (EVs) are nanoscale vesicles that are potential candidates for cell-free tissue regeneration strategies. They may be used for repairing damaged tissues and regulating the body's immune system and bone-related metabolic activities. Because of the ability of EVs to deliver bioactive signals and mediate intercellular communication, they can decipher the complex mechanisms of interaction within the “osteoimmune system” at the molecular level. To address the lack of targeting ability caused by vesicle heterogeneity in the clinical applications of EVs, these nanoscopical entities may be modified by bioengineering techniques to optimize the interaction between bone repair and immunomodulation for improving treatment efficacy, specificity and safety. In the present review, the endogenous properties that make EVs natural delivery agents are outlined. Properties that may be improved by bioengineering are highlighted. The therapeutic applications of EVs in the rehabilitation of bone defects are discussed. The opportunities and challenges that need to be addressed for translating this field of research into clinical practice are brought into perspectives.

骨免疫学近年来发展迅速,主要研究骨骼与免疫系统之间的相互作用。细胞外囊泡(EVs)是纳米级囊泡,是无细胞组织再生策略的潜在候选者。它们可用于修复受损组织,调节人体免疫系统和与骨相关的代谢活动。由于ev具有传递生物活性信号和介导细胞间通讯的能力,它们可以在分子水平上破译“骨免疫系统”内复杂的相互作用机制。为了解决EVs在临床应用中由于囊泡异质性导致的靶向能力不足的问题,可以通过生物工程技术对这些纳米级实体进行修饰,优化骨修复与免疫调节之间的相互作用,从而提高治疗效果、特异性和安全性。本文综述了电动汽车作为天然递送剂的内源性特性。强调了可以通过生物工程改进的特性。讨论了EVs在骨缺损修复中的应用。将这一领域的研究转化为临床实践需要解决的机遇和挑战被带入观点。
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引用次数: 6
3D Bioprinting with Live Cells 活细胞3D生物打印
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.07.002
Alicia Persaud , Alexander Maus , Lia Strait , Donghui Zhu

In recent years, the shortage of available organs for transplant patients has grown exponentially across the globe. Consequently, the healthcare industry is in dire need of artificial substitutes. Many recent research studies and tissue engineering groups have decided to utilize 3D bioprinting to produce these artificial organs. This synthetic organ printing is made possible by advancements in the materials required for the constructs, the printing methodologies used to produce them, and the final physical structures’ varying properties. The cutting-edge research and technology related to 3D and 4D live cell bioprinting have recently allowed researchers to produce multiple types of artificial organs and tissues. These tissues can be utilized for drug screening and organ replacement applications. This article provides an extensive review of all the pertinent 3D live cell bioprinting technologies. First, we describe scaffolding methods and their comparison with the traditional technologies. Second, we explain the 3D bioprinting technology, its evolution, and its multiple types. Moreover, we describe the pros and cons of each bioprinting method. Third, we have discussed the critical bioink properties and their impact on the formation of 3D bioprinting models. In addition, we also describe the mechanical properties of bioprinters. Fourth, we have thoroughly discussed the various types of hydrogels and their properties. Every kind of hydrogel is utilized in specific applications, and we have presented a comprehensive list of its advantages and disadvantages. Fifth, we have discussed various applications of 3D bioprinting technology. We have considered a case study of human organs and elaborated on how bioprinters can revolutionize the organ replacement industry. Finally, we evaluated the possibility of 4D printing in the future organ industry, incorporating temporal factors into the bioprinting process.

近年来,全球范围内可供移植患者使用的器官短缺呈指数级增长。因此,医疗保健行业迫切需要人工替代品。许多最近的研究和组织工程小组已经决定利用3D生物打印来生产这些人造器官。这种合成器官的打印是由结构所需材料的进步,用于生产它们的打印方法,以及最终物理结构的不同特性而实现的。最近,与3D和4D活细胞生物打印相关的前沿研究和技术使研究人员能够生产多种类型的人造器官和组织。这些组织可用于药物筛选和器官替代应用。本文提供了所有相关的3D活细胞生物打印技术的广泛回顾。首先,介绍了支架法及其与传统支架法的比较。其次,我们解释了3D生物打印技术,它的发展,以及它的多种类型。此外,我们还描述了每种生物打印方法的优缺点。第三,我们讨论了生物墨水的关键特性及其对3D生物打印模型形成的影响。此外,我们还描述了生物打印机的机械性能。第四,我们深入地讨论了各种类型的水凝胶及其性质。每种水凝胶都有特定的应用,我们已经给出了它的优点和缺点的综合列表。第五,我们讨论了3D生物打印技术的各种应用。我们考虑了一个人体器官的案例研究,并详细阐述了生物打印机如何彻底改变器官替代行业。最后,我们评估了4D打印在未来器官行业的可能性,将时间因素纳入生物打印过程。
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引用次数: 16
Ellipsoidal porous patch with anisotropic cell inducing ability for inhibiting skin scar formation 具有各向异性细胞诱导能力的椭球状多孔贴片
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.06.003
Wanqing Weng , Junjie Chi , Xiaocheng Wang , Keqing Shi , Fangfu Ye , Yuanjin Zhao

Scar formation has always been a difficult point to overcome in the field of clinical wound care. Here, we present an ellipsoidal porous patch with cell inducing ability for inhibiting scar formation. The patch was prepared by stretching a poly (lactic-co-glycolic acid) (PLGA) inverse opal film at the glass transition temperature to form a neatly arranged three-dimensional ellipsoidal porous structure. Such anisotropic structure showed dramatic capability in directing cell growth and arrangement by reconstructing cell morphology. Besides, the proliferation of cells growing on the stretched patch was significantly suppressed without cell cytotoxicity. In addition, benefitting from the abundant and connected nanopores, the patch could be imparted with a potent ability to promote cell migration by encapsulating fibroblast growth factor 2 (FGF2) via the second filling of functional gelatin methacryloyl (GelMA) hydrogel into its scaffold. In a typical scar model, we have demonstrated that the resultant patch performed well in inhibiting scar formation characterized by inhibiting the excessive proliferation of fibroblasts, decreasing the deposition of type I collagen, reducing the scar index and achieved complete tissue reconstruction. These results indicate the anisotropic inverse opal patch has an excellent application prospect in inhibiting scar formation during wound repair.

瘢痕形成一直是临床创面护理领域的一个难点。在这里,我们提出了一种具有细胞诱导能力的椭球状多孔贴片,可以抑制疤痕的形成。通过在玻璃化转变温度下拉伸聚乳酸-羟基乙酸(PLGA)反蛋白石膜,制备出排列整齐的三维椭球状多孔结构。这种各向异性结构通过重构细胞形态,表现出对细胞生长和排列的指导作用。此外,在拉伸膜片上生长的细胞增殖受到明显抑制,且无细胞毒性。此外,得益于丰富且连接的纳米孔,该贴片可以通过将功能性明胶甲基丙烯酰(GelMA)水凝胶第二次填充到其支架中,从而将成纤维细胞生长因子2 (FGF2)包裹起来,从而具有促进细胞迁移的强大能力。在一个典型的疤痕模型中,我们已经证明,所得到的贴片具有良好的抑制疤痕形成的作用,其特征是抑制成纤维细胞的过度增殖,减少I型胶原的沉积,降低疤痕指数,实现完全的组织重建。结果表明,各向异性反蛋白石贴片在抑制创面修复过程中瘢痕形成方面具有良好的应用前景。
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引用次数: 7
Recent advances in chiral aggregation-induced emission fluorogens 手性聚集诱导排放氟化物的研究进展
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.07.003
Rui Hu , Yuncong Yuan , Meijia Gu , You-Quan Zou

Over the past decade, aggregation-induced emission (AIE) molecules have played a pivotal role in bioimaging, anti-microbial, and photodynamic therapy, and have been at the forefront of several disciplines worldwide. When combined with chiral moieties, they can easily collide with dazzling sparks and exhibit exceptional and unique advantages. In the application of chiral recognition and measurement of enantiomeric excess, it can identify chiral molecules visually based on color change and precipitation reaction, quantitatively analyze chiral molecules while determining the enantiomeric composition based on the fluorescence intensity change at different wavelengths, and obtain two parameters about chiral molecules from one measurement, thereby demonstrating its high selectivity, sensitivity and accuracy in chiral identification. In the field of organic circularly polarized luminescent (CPL) materials, the asymmetry (glum) of common organic light emitting elements is usually between 10−5 and 10−2, whereas the CPL asymmetry factor (glum) of chiral AIE fluorogens (AIEgens) can reach 1.42, which is very close to the theoretical value of 2. Therefore, the combination of chiral elements and luminescent groups promotes their adoption in the field of organic CPL materials. Herein we have summarized the recent applications of chiral AIEgens in both chiral molecule recognition and circularly polarized organic light-emitting diode (CP-OLED) in order to provide future researchers with a more comprehensive and detailed understanding of chiral AIEgens and to encourage more scientists to contribute to the development of AIEgens.

在过去的十年中,聚集诱导发射(AIE)分子在生物成像、抗微生物和光动力治疗中发挥了关键作用,并且在世界范围内处于几个学科的前沿。当与手性基团结合时,它们很容易碰撞出耀眼的火花,表现出卓越而独特的优势。在对映体过量的手性识别和测量应用中,可以根据颜色变化和沉淀反应直观地识别手性分子,根据不同波长下荧光强度变化确定对映体组成的同时对手性分子进行定量分析,一次测量即可获得手性分子的两个参数,在手性识别中具有较高的选择性、灵敏度和准确性。在有机圆极化发光(CPL)材料领域,普通有机发光元件的不对称系数(glum)通常在10−5 ~ 10−2之间,而手性AIE氟化物(AIEgens)的CPL不对称系数(glum)可达1.42,非常接近理论值2。因此,手性元素与发光基团的结合促进了它们在有机CPL材料领域的应用。本文对近年来手性光源在手性分子识别和圆偏振有机发光二极管(CP-OLED)中的应用进行了综述,以期为今后的研究人员提供更全面、更详细的了解手性光源,并鼓励更多的科学家为手性光源的发展做出贡献。
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引用次数: 0
A versatile approach for temporary storage and shipping of in vitro cultured cells, cell sheets and tissue engineered constructs – a preliminary report 临时储存和运输体外培养细胞、细胞片和组织工程构建物的通用方法-初步报告
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.07.001
Anju MS , Athira RK , Ramesh Babu V , Anil Kumar PR , Naresh Kasoju

Temporary storage/ shipping of cell/ tissue engineering products from bench to bedside is a key aspect of regenerative medicine. The current proof-of-concept study presents a multipurpose device for temporary storage/ shipping of cell culture dishes containing cell/ tissue constructs. The device, made with readily available raw materials, contains three elements viz. a specialized lid, polymeric plates having grooves and a set of nuts and bolts. As part of the performance evaluation, the device was first subjected to a simulated storage/ shipping process, wherein the leak-proof and aseptic containment of the contents was demonstrated. Subsequently, the setup was used for temporary storage/ shipping of dishes having (a) L929 cell monolayers cultured on treated surfaces, (b) SIRC, HaCaT and A549 cell sheets cultured on thermo-responsive surfaces, (c) HOS-cell encapsulated agar gels and (d) HOS-cell seeded silk fibroin mats. The results showed that the health of cell monolayers/ cell sheets/ tissue constructs after the process was comparable to that before the process. The device was scalable, simple to handle, can be made for a single or multi-use purpose, and can be resizable to load other culture vessels. The design of the storage/ shipping device described in this report thus offers versatile features and applications.

细胞/组织工程产品从实验室到床边的临时储存/运输是再生医学的一个关键方面。目前的概念验证研究提出了一种多用途设备,用于临时储存/运输含有细胞/组织结构的细胞培养皿。该装置由现成的原材料制成,包含三个元素,即一个专门的盖子,有凹槽的聚合板和一组螺母和螺栓。作为性能评估的一部分,设备首先进行了模拟存储/运输过程,其中演示了内容物的防泄漏和无菌容器。随后,该装置用于临时储存/运输(a)在处理表面培养的L929细胞单层,(b)在热响应表面培养的SIRC, HaCaT和A549细胞片,(c) hos细胞包封琼脂凝胶和(d) hos细胞种子丝素垫。结果表明,处理后的细胞单层/细胞片/组织结构的健康状况与处理前相当。该装置可扩展,操作简单,可用于单一或多用途,并且可以调整大小以装载其他培养容器。因此,本报告中描述的存储/运输设备的设计提供了多种功能和应用。
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引用次数: 0
Programmable microfluidic manipulations for biomedical applications 生物医学应用的可编程微流控操作
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.06.001
Dagan Zhang , Wenzhao Li , Yixuan Shang , Luoran Shang

Fluid manipulation plays an important role in biomedical applications such as biochemical assays, medical diagnostics, and drug development. Programmable fluidic manipulation at the microscale is highly desired in both fundamental and practical aspects. In this paper, we summarize some of the latest studies that achieve programmable fluidic manipulation through intricate capillaric circuits design, construction of biomimetic metasurface, and responsive surface wettability control. We highlight the working principle of each system and concisely discuss their design criterion, technical improvements, and implications for future study. We envision that with multidisciplinary efforts, microfluidics would continue to bring vast opportunities to biomedical fields and make contributions to human health.

流体操作在生物医学应用中发挥着重要作用,如生化分析、医学诊断和药物开发。可编程的流体操纵在微尺度是高度期望在基础和实际方面。在本文中,我们总结了通过复杂的毛细管电路设计、仿生超表面的构建和响应性表面润湿性控制来实现可编程流体操纵的一些最新研究。我们重点介绍了每个系统的工作原理,并简要讨论了它们的设计标准、技术改进和对未来研究的启示。我们期待在多学科的共同努力下,微流控将继续为生物医学领域带来巨大的机遇,为人类健康做出贡献。
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引用次数: 33
Development of fish collagen in tissue regeneration and drug delivery 鱼类胶原蛋白在组织再生和药物传递中的研究进展
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.05.002
Meison Furtado, Liang Chen, Zehao Chen, Ao Chen, Wenguo Cui

Tissues rely on collagen for structural and biological integrity, as well as for function and strength. Several collagen sources have been investigated due to its wide variety of applications, such as collagen from cows and pigs. However, mammalian-based collagen has been limited by diseases like bovine spongiform encephalopathy (BSE) and other religious limitations. Hence, fish collagen has caught the attention of the research community because it is easy to extract, has a high level of collagen content, excellent absorption properties, a low molecular weight, biocompatibility, little risk of disease transmission from animals to humans, negligible environmental contamination, and fewer ethical and religious concerns, posing as an ideal resource for product development. This review focuses on the growing role of marine collagen in the advances of various biomedical applications, such as drug delivery, tissue engineering, regeneration, and wound healing, which will be covered in depth.

组织依赖于胶原蛋白的结构和生物完整性,以及功能和强度。由于其广泛的应用,已经研究了几种胶原蛋白来源,例如来自牛和猪的胶原蛋白。然而,基于哺乳动物的胶原蛋白一直受到牛海绵状脑病(BSE)等疾病和其他宗教限制的限制。因此,鱼类胶原蛋白已经引起了研究界的关注,因为它易于提取,胶原蛋白含量高,吸收性能好,分子量低,生物相容性好,动物向人类传播疾病的风险小,环境污染可忽略,伦理和宗教问题较少,是产品开发的理想资源。本文综述了海洋胶原蛋白在药物传递、组织工程、再生和伤口愈合等生物医学领域的应用进展。
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引用次数: 70
Osteoblastic microRNAs in skeletal diseases: Biological functions and therapeutic implications 成骨细胞microrna在骨骼疾病中的生物学功能和治疗意义
Q1 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.engreg.2022.06.002
Lei Yu , Wenming Li , Peng Yang , Wei Zhang , Huaqiang Tao , Gaoran Ge , Huilin Yang , Jiaxiang Bai , Huaiyu Wang , Dechun Geng

Skeletal diseases normally represents a grievous imbalance between osteoblasts for bone formation and osteoclasts for bone resorption. A lack of osteogenic function can make it difficult to repair pathological bone erosion. Therefore, substantial efforts have been made to remedy these issues, with the aid of bioactive molecules, herbs and materials. Following recent insights, the importance of epigenetic gene regulation is increasingly evident, especially microRNAs. MicroRNAs can silence target genes by inhibiting mRNA translation or degrading mRNA molecules by binding to their 3′-untranslated region. There is accumulating evidence indicating that the miRNAs significantly involved in osteogenic gene expression, signaling pathway intervention and programmed cell death. Besides, numerous new target drugs (microRNA inhibitors or agonists) have been proposed to exploit its value in skeletal physiology and pathology. In this review, we mainly discuss the role of microRNAs in the context of skeletal disease-associated osteoblast differentiation, the applications of microRNA polymorphisms as biomarkers for diagnostic and therapeutic targets, and the challenges to meet this goal. Our summary provides novel horizon for improving the therapeutic effect of microRNAs, which may be beneficial to the further clinical translation of microRNAs in the treatments of skeletal diseases.

骨骼疾病通常表现为骨形成的成骨细胞和骨吸收的破骨细胞之间的严重失衡。缺乏成骨功能会使病理性骨侵蚀难以修复。因此,在生物活性分子、草药和材料的帮助下,已经做出了大量的努力来纠正这些问题。根据最近的见解,表观遗传基因调控的重要性日益明显,特别是microrna。microrna可以通过抑制mRNA翻译或通过结合mRNA分子的3 ' -非翻译区降解mRNA分子来沉默靶基因。越来越多的证据表明,这些mirna显著参与成骨基因表达、信号通路干预和细胞程序性死亡。此外,许多新的靶点药物(microRNA抑制剂或激动剂)被提出,以开发其在骨骼生理学和病理学上的价值。在这篇综述中,我们主要讨论microRNA在骨骼疾病相关成骨细胞分化中的作用,microRNA多态性作为诊断和治疗靶点的生物标志物的应用,以及实现这一目标所面临的挑战。我们的总结为提高microrna的治疗效果提供了新的思路,这可能有利于microrna在骨骼疾病治疗中的进一步临床翻译。
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引用次数: 4
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Engineered regeneration
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