bioink

生物墨水
  • 文章类型: Journal Article
    3D打印可以通过允许具有成本效益的个性化医疗彻底改变,定制的组织工程构造。然而,生物聚合水凝胶的有限可用性和多样性限制了生物墨水的种类和应用。在这项研究中,我们引入了一种用于3D生物打印的复合生物墨水,结合称为甲基丙烯酸酯化粘蛋白(MuMA)的粘蛋白(Mu)的光交联衍生物和透明质酸(HA)。较少探索的粘蛋白负责粘液的水凝胶性质,并且由于其丰富的特征而具有用作生物墨水材料的潜力。HA,一种重要的细胞外基质成分,是粘膜粘附性和增强油墨粘度和可印刷性。用405nm光的光交联使打印的支架稳定而不损伤细胞。流变试验揭示了剪切稀化行为,通过添加HA来帮助打印过程中的细胞保护并改善MuMA生物墨水粘度。打印结构表现出有利于养分运输和细胞迁移的多孔行为。在磷酸盐缓冲盐水中4周后,支架保留了70%的质量,强调稳定性。与肺上皮细胞(L-132)的生物相容性试验证实细胞附着和生长,表明肺组织工程的适用性。可以预见,生物墨水的多功能性可能会导致肺组织工程和各种其他生物医学应用的显着进步。
    3D printing can revolutionize personalized medicine by allowing cost-effective, customized tissue-engineering constructs. However, the limited availability and diversity of biopolymeric hydrogels restrict the variety and applications of bioinks. In this study, we introduce a composite bioink for 3D bioprinting, combining a photo-cross-linkable derivative of Mucin (Mu) called Methacrylated Mucin (MuMA) and Hyaluronic acid (HA). The less explored Mucin is responsible for the hydrogel nature of mucus and holds the potential to be used as a bioink material because of its plethora of features. HA, a crucial extracellular matrix component, is mucoadhesive and enhances ink viscosity and printability. Photo-cross-linking with 405 nm light stabilizes the printed scaffolds without damaging cells. Rheological tests reveal shear-thinning behavior, aiding cell protection during printing and improved MuMA bioink viscosity by adding HA. The printed structures exhibited porous behavior conducive to nutrient transport and cell migration. After 4 weeks in phosphate-buffered saline, the scaffolds retain 70% of their mass, highlighting stability. Biocompatibility tests with lung epithelial cells (L-132) confirm cell attachment and growth, suggesting suitability for lung tissue engineering. It is envisioned that the versatility of bioink could lead to significant advancements in lung tissue engineering and various other biomedical applications.
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  • 文章类型: Journal Article
    由于目前皮肤创伤治疗方法的局限性,具有模拟天然皮肤组织的细胞外基质(ECM)和机械性能的伤口愈合制剂是非常有价值的。这里,一种新的仿生水凝胶制剂已经开发的基础上,琼脂糖-胶原蛋白I型(AC)与皮肤ECM相关的成分的混合物:硫酸皮肤素(DS),透明质酸(HA),和弹性蛋白(EL)在皮肤组织工程(TE)中的应用。通过将AC水凝胶与DS组合设计不同的配方,HA,和EL。细胞活力,血液相容性,物理化学,机械,和伤口愈合特性进行了研究。最后,使用Ag-ColI-DS-HA-EL(ACDHE)制剂开发负载有成纤维细胞和间充质基质细胞的双层水凝胶。ACDHE水凝胶显示出最佳的体外结果和可接受的物理化学性质。此外,它的机械行为接近人类天然皮肤,并表现出良好的细胞相容性。环境扫描电子显微镜(ESEM)分析显示出多孔的微观结构,可以维持细胞生长和ECM样结构的产生。这些发现证明了ACDHE水凝胶制剂用于诸如可注射水凝胶或生物墨水的应用以产生用于皮肤TE的载有细胞的结构的潜力。
    Due to the limitations of the current skin wound treatments, it is highly valuable to have a wound healing formulation that mimics the extracellular matrix (ECM) and mechanical properties of natural skin tissue. Here, a novel biomimetic hydrogel formulation has been developed based on a mixture of Agarose-Collagen Type I (AC) combined with skin ECM-related components: Dermatan sulfate (DS), Hyaluronic acid (HA), and Elastin (EL) for its application in skin tissue engineering (TE). Different formulations were designed by combining AC hydrogels with DS, HA, and EL. Cell viability, hemocompatibility, physicochemical, mechanical, and wound healing properties were investigated. Finally, a bilayered hydrogel loaded with fibroblasts and mesenchymal stromal cells was developed using the Ag-Col I-DS-HA-EL (ACDHE) formulation. The ACDHE hydrogel displayed the best in vitro results and acceptable physicochemical properties. Also, it behaved mechanically close to human native skin and exhibited good cytocompatibility. Environmental scanning electron microscopy (ESEM) analysis revealed a porous microstructure that allows the maintenance of cell growth and ECM-like structure production. These findings demonstrate the potential of the ACDHE hydrogel formulation for applications such as an injectable hydrogel or a bioink to create cell-laden structures for skin TE.
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  • 文章类型: Journal Article
    肿瘤模型的出现极大地促进了治疗药物和方法的发展。然而,由于其固有的复杂性,建立一个可以完全复制肿瘤组织情况的模型仍然极具挑战性。随着组织工程学的发展,生物打印技术的进步促进了肿瘤模型的升级。本文重点介绍生物打印的最新进展,特别强调3D肿瘤模型的构建,并强调了这两种技术的集成。此外,它讨论了相关技术的挑战和未来方向,同时还强调通过类似于体外器官的3D肿瘤模型的出现来有效地重建肿瘤微环境,从而加速新的抗癌疗法的发展。
    The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.
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  • 文章类型: Journal Article
    UNASSIGNED: To review the research progress on the application of three-dimensional (3D) bioprinting technology in auricle repair and reconstruction.
    UNASSIGNED: The recent domestic and international research literature on 3D printing and auricle repair and reconstruction was extensively reviewed, and the concept of 3D bioprinting technology and research progress in auricle repair and reconstruction were summarized.
    UNASSIGNED: The auricle possesses intricate anatomical structure and functionality, necessitating precise tissue reconstruction and morphological replication. Hence, 3D printing technology holds immense potential in auricle reconstruction. In contrast to conventional 3D printing technology, 3D bioprinting technology not only enables the simulation of auricular outer shape but also facilitates the precise distribution of cells within the scaffold during fabrication by incorporating cells into bioink. This approach mimics the composition and structure of natural tissues, thereby favoring the construction of biologically active auricular tissues and enhancing tissue repair outcomes.
    UNASSIGNED: 3D bioprinting technology enables the reconstruction of auricular tissues, avoiding potential complications associated with traditional autologous cartilage grafting. The primary challenge in current research lies in identifying bioinks that meet both the mechanical requirements of complex tissues and biological criteria.
    UNASSIGNED: 对3D生物打印技术在耳廓修复重建方面的应用研究进展作一综述。.
    UNASSIGNED: 广泛查阅近年来国内外3D打印与耳廓修复重建相关研究文献,对3D生物打印技术概念及其在耳廓修复重建中的应用研究进展进行总结。.
    UNASSIGNED: 耳廓具有复杂解剖结构和功能,需要精确的组织重建和形态复制,因此 3D打印技术在耳廓修复重建方面具有巨大应用潜力。与传统3D打印技术相比,3D生物打印技术不仅能模拟耳廓外形结构,还能将细胞与材料混合打印,在支架成型过程中实现细胞在支架内部精准分布,模拟天然组织组成及结构,更有利于构建具有生物活性功能的耳廓组织,从而提高修复效果。.
    UNASSIGNED: 3D生物打印技术可以重建耳廓组织,能避免传统自体软骨移植相关并发症,寻找既符合耳廓组织机械性要求,又符合生物要求的生物墨水是目前研究的主要挑战。.
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  • 文章类型: Journal Article
    在组织工程的背景下,生物制造技术用于处理基于水凝胶的基质中的细胞,被称为生物墨水,变成复杂的3D结构。目的是产生功能性组织模型或甚至整个器官。生物组织的再生生产遵循最终决定功能组织成熟的众多标准。这些标准是生物学性质的,例如不同细胞类型在生理和机械上合适的基质中的仿生空间定位,使组织成熟。此外,处理,技术程序和生物材料的结合,由于细胞对压力敏感,因此具有很大的挑战性,例如来自剪切力和拉力,这可能会影响他们的活力。另一方面,追求高分辨率,为随后的组织成熟创造最佳条件。从分析的角度来看,在进行复杂的生物测试之前,首先调查生物墨水的打印行为是谨慎的。根据我们的发现,传统的剪切流变测试不足以完全表征生物墨水的印刷行为。出于这个原因,我们开发了光学方法,与已经开发的测试互补,允许对打印质量进行量化,并进一步对生物墨水进行粘弹性建模。
    In the context of tissue engineering, biofabrication techniques are employed to process cells in hydrogel-based matrices, known as bioinks, into complex 3D structures. The aim is the production of functional tissue models or even entire organs. The regenerative production of biological tissues adheres to a multitude of criteria that ultimately determine the maturation of a functional tissue. These criteria are of biological nature, such as the biomimetic spatial positioning of different cell types within a physiologically and mechanically suitable matrix, which enables tissue maturation. Furthermore, the processing, a combination of technical procedures and biological materials, has proven highly challenging since cells are sensitive to stress, for example from shear and tensile forces, which may affect their vitality. On the other hand, high resolutions are pursued to create optimal conditions for subsequent tissue maturation. From an analytical perspective, it is prudent to first investigate the printing behavior of bioinks before undertaking complex biological tests. According to our findings, conventional shear rheological tests are insufficient to fully characterize the printing behavior of a bioink. For this reason, we have developed optical methods that, complementarily to the already developed tests, allow for quantification of printing quality and further viscoelastic modeling of bioinks.
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  • 文章类型: Journal Article
    抗肿瘤药物的评价对其开发和临床指导至关重要。肿瘤类器官模型由于其更好地模拟真实肿瘤组织的能力而获得越来越多的关注。以及更低的时间和经济成本,弥补了细胞系和异种移植模型的不足。然而,目前基于Matrigel的肿瘤类器官培养物由于缓慢的凝胶化和低的机械强度而在与高通量工程方法匹配方面具有局限性。这里,我们提出了一种用于培养结直肠癌类器官的新型复合生物墨水,该生物墨水提供了接近真实组织生长条件的环境,并表现出优异的光交联特性,可快速形成凝胶。最重要的是,打印后复合生物墨水中的肿瘤类器官活力高达97%,这也保持了多细胞极性结构与Matrigel中的传统培养方法一致。使用这种载有类器官的复合生物墨水进行3D生物打印,我们通过与临床使用的结直肠癌治疗药物进行验证,证明了该药物评价模型的可行性.我们的结果表明,复合生物墨水可以使用3D生物打印有效培养肿瘤类器官,有可能取代不太可靠的手工操作,以促进肿瘤类器官在药物开发和临床指导中的应用。
    The evaluation of anti-tumor drugs is critical for their development and clinical guidance. Tumor organoid models are gaining increased attention due to their ability to better mimic real tumor tissues, as well as lower time and economic costs, which makes up for the shortcomings of cell lines and xenograft models. However, current tumor organoid cultures based on the Matrigel have limitations in matching with high-throughput engineering methods due to slow gelation and low mechanical strength. Here, we present a novel composite bioink for culturing colorectal cancer organoids that provides an environment close to real tissue growth conditions and exhibits excellent photocrosslinking properties for rapid gel formation. Most importantly, the tumor organoids viability in the composite bioink after printing was as high as 97%, which also kept multicellular polar structures consistent with traditional culture methods in the Matrigel. Using 3D bioprinting with this composite bioink loaded with organoids, we demonstrated the feasibility of this drug evaluation model by validating it with clinically used colorectal cancer treatment drugs. Our results suggested that the composite bioink could effectively cultivate tumor organoids using 3D bioprinting, which had the potential to replace less reliable manual operations in promoting the application of tumor organoids in drug development and clinical guidance.
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  • 文章类型: Journal Article
    人们对生物墨水的生产越来越感兴趣,一方面,是生物相容的,另一方面,具有机械性能,可以生产出稳定的构建体,这些构建体在移植后可以长时间存活。虽然选择正确的材料对于生物打印至关重要,还有另一个同样重要的问题,目前正在广泛研究-血管系统的结合到制造的支架。因此,在下面的手稿中,我们提出了具有独特物理化学和生物学特性的生物墨水的研究结果。在这篇文章中,使用生物墨水B测试两种接种细胞的方法,并在生物打印整个模型后进行接种。孵育2、5、8或24小时后,在测试系统中使用流动介质。在实验试验结束时,对于每个时间变体,运河储存在甲醛中,进行免疫组织化学染色以检查管壁和屋顶上细胞的存在。细胞粘附于两种纤维排列方式;然而,与5小时孵育和细胞中间铺板的平行生物打印导致更好的粘附效率。对于此测试变体,粘附的细胞百分比比其他分析的变体高至少20%。此外,对于这种变体,发现从测试模型中洗掉的最低百分比的活细胞。重要的是,苏木精和伊红染色显示培养8天后,细胞均匀分布在整个运河屋顶。我们的研究清楚地表明,促进新生血管形成的细胞有效地粘附于基于ECM的胰腺生物墨水。总结提出的结果,已证明,所提出的生物墨水组合物可用于生物打印具有由内皮细胞和成纤维细胞形成的血管系统的仿生器官。
    There is a growing interest in the production of bioinks that on the one hand, are biocompatible and, on the other hand, have mechanical properties that allow for the production of stable constructs that can survive for a long time after transplantation. While the selection of the right material is crucial for bioprinting, there is another equally important issue that is currently being extensively researched-the incorporation of the vascular system into the fabricated scaffolds. Therefore, in the following manuscript, we present the results of research on bioink with unique physico-chemical and biological properties. In this article, two methods of seeding cells were tested using bioink B and seeding after bioprinting the whole model. After 2, 5, 8, or 24 h of incubation, the flow medium was used in the tested systems. At the end of the experimental trial, for each time variant, the canals were stored in formaldehyde, and immunohistochemical staining was performed to examine the presence of cells on the canal walls and roof. Cells adhered to both ways of fiber arrangement; however, a parallel bioprint with the 5 h incubation and the intermediate plating of cells resulted in better adhesion efficiency. For this test variant, the percentage of cells that adhered was at least 20% higher than in the other analyzed variants. In addition, it was for this variant that the lowest percentage of viable cells was found that were washed out of the tested model. Importantly, hematoxylin and eosin staining showed that after 8 days of culture, the cells were evenly distributed throughout the canal roof. Our study clearly shows that neovascularization-promoting cells effectively adhere to ECM-based pancreatic bioink. Summarizing the presented results, it was demonstrated that the proposed bioink compositions can be used for bioprinting bionic organs with a vascular system formed by endothelial cells and fibroblasts.
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  • 文章类型: Journal Article
    丝素蛋白(SF)是从家蚕丝线中提取的天然蛋白质。从其在纺织工业中的普遍使用来看,它是一种生物材料,具有有前途的生化和机械性能,可应用于组织工程和再生医学领域。在这项研究中,我们首次评估了SF对含有心脏球体的心脏生物墨水制剂的影响。首先,我们评估SF添加是否在含有藻酸盐(Alg)和明胶(Gel)的水凝胶的结构和弹性特性中起作用。然后,我们测试生物打印的含SF水凝胶的可印刷性和耐久性。最后,我们评估了在Alg-Gel水凝胶中添加SF是否可以控制细胞活力和心脏球体的功能。我们的发现表明,向Alg-Gel水凝胶中添加1%(w/v)SF会使它们更具弹性,而不会影响细胞活力。然而,SF-Alg-Gel水凝胶中心脏球体的缩短分数(FS%)增加而不影响其收缩频率,表明3D培养物中收缩功能的改善。总之,我们的发现支持了一个有希望的途径,将含有SF的生物墨水用于心脏应用,具有控制心脏生物墨水的机械和细胞特征的能力。
    Silk fibroin (SF) is a natural protein extracted fromBombyx morisilkworm thread. From its common use in the textile industry, it emerged as a biomaterial with promising biochemical and mechanical properties for applications in the field of tissue engineering and regenerative medicine. In this study, we evaluate for the first time the effects of SF on cardiac bioink formulations containing cardiac spheroids (CSs). First, we evaluate if the SF addition plays a role in the structural and elastic properties of hydrogels containing alginate (Alg) and gelatin (Gel). Then, we test the printability and durability of bioprinted SF-containing hydrogels. Finally, we evaluate whether the addition of SF controls cell viability and function of CSs in Alg-Gel hydrogels. Our findings show that the addition of 1% (w/v) SF to Alg-Gel hydrogels makes them more elastic without affecting cell viability. However, fractional shortening (FS%) of CSs in SF-Alg-Gel hydrogels increases without affecting their contraction frequency, suggesting an improvement in contractile function in the 3D cultures. Altogether, our findings support a promising pathway to bioengineer bioinks containing SF for cardiac applications, with the ability to control mechanical and cellular features in cardiac bioinks.
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  • 文章类型: Journal Article
    背景技术基于数字光处理(DLP)的(生物)打印机的进步使得能够使用宽范围的光敏生物墨水以高分辨率打印复杂结构。DLP生物打印机的典型设置包括充满液体生物墨水的大桶或储液器,这在与生物墨水合成相关的成本方面提出了挑战,高浪费,和重力诱导的细胞沉降,污染,或在印刷过程中生物墨水粘度的变化。这里,我们报告无增值税,低音量,无浪费的液滴生物打印方法,能够使用模型生物墨水以高分辨率快速打印3D软结构。建立了多相多体耗散粒子动力学(mDPD)模型,以模拟基于液滴的DLP打印的动态过程,并阐明了表面润湿性和生物墨水粘度的作用。过程变量,如光强度,光引发剂浓度,和生物墨水配方进行了优化,以打印3D软结构(〜0.4至3kPa),XY分辨率为38±1.5μm,Z分辨率为237±5.4µm。为了展示它的多功能性,液滴生物打印用于打印一系列无细胞3D结构,如晶格立方体,玛雅金字塔,心形结构,和带有内皮化通道的微流控芯片。液滴生物打印,使用模型C3H/10T1/2细胞进行,表现出高活力(90%)和细胞扩散。此外,具有内衬内皮细胞的内部通道网络的微流体装置显示出强大的单层形成,而载有成骨细胞的构建体在成骨诱导时显示出矿物质沉积。总的来说,液滴生物打印可能是低成本的,没有浪费,易于使用,方法为一系列生物医学应用制作定制的生物打印构建体。
    Advances in digital light projection(DLP) based (bio) printers have made printing of intricate structures at high resolution possible using a wide range of photosensitive bioinks. A typical setup of a DLP bioprinter includes a vat or reservoir filled with liquid bioink, which presents challenges in terms of cost associated with bioink synthesis, high waste, and gravity-induced cell settling, contaminations, or variation in bioink viscosity during the printing process. Here, we report a vat-free, low-volume, waste-free droplet bioprinting method capable of rapidly printing 3D soft structures at high resolution using model bioinks and model cells. A multiphase many-body dissipative particle dynamics model was developed to simulate the dynamic process of droplet-based DLP printing and elucidate the roles of surface wettability and bioink viscosity. Process variables such as light intensity, photo-initiator concentration, and bioink formulations were optimized to print 3D soft structures (∼0.4-3 kPa) with a typical layer thickness of 50µm, an XY resolution of 38 ± 1.5μm and Z resolution of 237 ± 5.4µm. To demonstrate its versatility, droplet bioprinting was used to print a range of acellular 3D structures such as a lattice cube, a Mayan pyramid, a heart-shaped structure, and a microfluidic chip with endothelialized channels. Droplet bioprinting, performed using model C3H/10T1/2 cells, exhibited high viability (90%) and cell spreading. Additionally, microfluidic devices with internal channel networks lined with endothelial cells showed robust monolayer formation while osteoblast-laden constructs showed mineral deposition upon osteogenic induction. Overall, droplet bioprinting could be a low-cost, no-waste, easy-to-use, method to make customized bioprinted constructs for a range of biomedical applications.
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  • 文章类型: Journal Article
    三维(3D)生物打印已经成为一种革命性的增材制造技术,可以潜在地实现再生医学中改变生活的医学治疗。它应用组织工程的原理,以逐层的方式打印组织和器官。这篇综述的重点是目前可用的各种3D生物打印技术,不同的生物材料,细胞,和可用于开发组织特异性生物墨水的生长因子,应用这些技术的不同场所,以及这项技术面临的挑战。
    Three-dimensional (3D) bioprinting has emerged as a revolutionary additive manufacturing technology that can potentially enable life-changing medical treatments in regenerative medicine. It applies the principles of tissue engineering for the printing of tissues and organs in a layer-by-layer manner. This review focuses on the various 3D bioprinting technologies currently available, the different biomaterials, cells, and growth factors that can be utilized to develop tissue-specific bioinks, the different venues for applying these technologies, and the challenges this technology faces.
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