bioink

生物墨水
  • 文章类型: Journal Article
    背景随着三维(3D)生物打印成为实现可预测的再生结果的个性化治疗的最终巅峰,寻找组织特异性生物墨水的工作正在进行中。去细胞化的细胞外基质(DECM),提供了固有的仿生线索,获得了相当多的关注。本研究的目的是比较三种不同的去矿质方案的功效,以获得用于骨组织工程应用的DECM。方法使用三种去矿质方案处理山羊股骨以获得DECM。A组用脱矿质溶液以40rpm的速度处理14天,B组用冻融循环和0.05M盐酸(HCl)和2.4mM乙二胺四乙酸(EDTA)以40rpm的速度进行60天,和C组用0.1MHCl在40rpm下持续三天。洗涤后,中和,0.05%胰蛋白酶-EDTA处理24小时,和冻干,获得DECM。评估包括扫描电子显微镜(SEM)分析,能量色散X射线(EDX)分析,苏木精和伊红(H&E)染色,和生物相容性分析。结果进行比较分析,C组遵循的方案显示出良好的表面性能,具有专利和相互连接良好的孔,平均孔径为218.87µm。C组还发现碳和氧是主要成分,含有痕量钙,证明充分的去矿化。在组织学分析下,C组进一步显示最佳的去矿化和去细胞化,同时保持生物相容性。在C组中获得的DECM应进一步加工用于生物打印应用。结论本研究中探索的三个方案具有潜力,C组的协议展示了基于DECM的生物墨水应用的最有希望。需要进一步的研究来评估获得的DECM用于制备用于3D生物打印的组织特异性生物墨水的适用性。
    Background With three-dimensional (3D) bioprinting emerging as the ultimate pinnacle of personalised treatment for achieving predictable regenerative outcomes, the search for tissue-specific bioinks is on. Decellularised extracellular matrix (DECM), which provides the inherent biomimetic cues, has gained considerable attention. The objective of the present study was to compare the efficacy of three different demineralisation protocols to obtain DECM for bone tissue engineering applications.  Methodology Goat femurs were treated using three demineralisation protocols to obtain DECM. Group A was treated with demineralisation solution at 40 rpm for 14 days, Group B with freeze-thaw cycles and 0.05M hydrochloric acid (HCl) and 2.4 mM ethylenediamine tetra-acetic acid (EDTA) at 40 rpm for 60 days, and Group C with 0.1M HCl at 40 rpm for three days. After washing, neutralization, 0.05% trypsin-EDTA treatment for 24 hours, and lyophilisation, DECM was obtained. Assessments included scanning electron microscope (SEM) analysis, energy dispersive X-ray (EDX) analysis, hematoxylin and eosin (H&E) staining, and biocompatibility analysis.  Results On comparative analysis, the protocol followed by Group C revealed good surface properties with patent and well interconnected pores with an average pore size of 218.87µm. Group C also revealed carbon and oxygen as predominant components with trace amounts of calcium, proving adequate demineralisation. Group C further revealed optimal demineralisation and decellularisation under histological analysis while maintaining biocompatibility. DECM obtained in Group C should be further processed for bioprinting applications.  Conclusion The three protocols explored in this study hold potential, with Group C\'s protocol demonstrating the most promise for DECM-based bioink applications. Further research is needed to evaluate the suitability of the obtained DECM for preparing tissue-specific bioinks for 3D bioprinting.
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  • 文章类型: Journal Article
    透明质细胞,它们被认为起源于单核细胞/巨噬细胞谱系,在玻璃体胶原蛋白和透明质酸合成中起积极作用。在眼睛模型的3D生物打印期间获得与透明质细胞相容的生物墨水是具有挑战性的。在这项研究中,我们研究了基于软骨脱细胞细胞外基质(dECM)的生物墨水打印玻璃体模型的适用性.鉴于实现与玻璃体相同的3D结构和环境需要良好的可印刷性和生物相容性,我们检查了开发的基于dECM的生物墨水的机械和生物学特性。此外,我们提出了一种3D生物打印策略,用于支持细胞活力的体积玻璃体制造,透明度,和自我可持续性。由生物墨水微纤维组成的3D结构的构建导致体积玻璃体模拟物的透明度和透明质细胞样巨噬细胞活性提高,模仿真正的玻璃体.结果表明,我们的3D结构可以作为疾病模型中药物测试的平台,并证明所提出的印刷技术,利用基于dECM的生物墨水和体积玻璃体,有可能促进先进的眼睛模型的发展,用于未来的漂浮物形成和视觉障碍的研究。
    Hyalocytes, which are considered to originate from the monocyte/macrophage lineage, play active roles in vitreous collagen and hyaluronic acid synthesis. Obtaining a hyalocyte-compatible bioink during the 3D bioprinting of eye models is challenging. In this study, we investigated the suitability of a cartilage-decellularized extracellular matrix (dECM)-based bioink for printing a vitreous body model. Given that achieving a 3D structure and environment identical to those of the vitreous body necessitates good printability and biocompatibility, we examined the mechanical and biological properties of the developed dECM-based bioink. Furthermore, we proposed a 3D bioprinting strategy for volumetric vitreous body fabrication that supports cell viability, transparency, and self-sustainability. The construction of a 3D structure composed of bioink microfibers resulted in improved transparency and hyalocyte-like macrophage activity in volumetric vitreous mimetics, mimicking real vitreous bodies. The results indicate that our 3D structure could serve as a platform for drug testing in disease models and demonstrate that the proposed printing technology, utilizing a dECM-based bioink and volumetric vitreous body, has the potential to facilitate the development of advanced eye models for future studies on floater formation and visual disorders.
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  • 文章类型: Journal Article
    三维生物打印通过实现复杂和功能性的人体组织和器官的制造,彻底改变了组织工程。成功的3D生物打印的重要组成部分是选择能够支持细胞增殖和活力的适当生物墨水。植物衍生生物材料,因为它们丰富,生物相容性,和可调属性,作为生物墨水的来源,因此提供优于动物衍生生物材料的优势,带有免疫原性的担忧。这篇综合综述探讨并分析了植物衍生的生物材料作为生物墨水用于人体组织3D生物打印的潜力。讨论了对这些材料进行改性和优化以增强可印刷性和生物功能。此外,在生物打印各种人体组织如骨骼中使用基于植物的生物材料的癌症研究和药物测试应用,软骨,皮肤,和血管组织的描述。挑战和限制,包括机械完整性,细胞活力,决议,和监管方面的担忧,以及克服它们的潜在策略,正在讨论。此外,这篇综述提供了对基于植物的dECM作为生物墨水的潜在用途的见解,未来的前景,以及将植物衍生的生物材料用于3D生物打印应用的新兴趋势。本文强调了植物衍生的生物材料作为用于人类组织的3D生物打印的生物墨水的潜力。然而,需要进一步的研究来优化它们的加工,标准化它们的属性,并评估其长期体内性能。植物衍生生物材料的不断进步有可能彻底改变组织工程,并促进各种临床应用的功能和再生疗法的开发。
    Three-dimensional bioprinting has revolutionized tissue engineering by enabling the fabrication of complex and functional human tissues and organs. An essential component of successful 3D bioprinting is the selection of an appropriate bioink capable of supporting cell proliferation and viability. Plant-derived biomaterials, because of their abundance, biocompatibility, and tunable properties, hold promise as bioink sources, thus offering advantages over animal-derived biomaterials, which carry immunogenic concerns. This comprehensive review explores and analyzes the potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues. Modification and optimization of these materials to enhance printability and biological functionality are discussed. Furthermore, cancer research and drug testing applications of the use of plant-based biomaterials in bioprinting various human tissues such as bone, cartilage, skin, and vascular tissues are described. Challenges and limitations, including mechanical integrity, cell viability, resolution, and regulatory concerns, along with potential strategies to overcome them, are discussed. Additionally, this review provides insights into the potential use of plant-based dECM as bioinks, future prospects, and emerging trends in the use of plant-derived biomaterials for 3D bioprinting applications. The potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues is highlighted herein. However, further research is necessary to optimize their processing, standardize their properties, and evaluate their long-term in vivo performance. Continued advancements in plant-derived biomaterials have the potential to revolutionize tissue engineering and facilitate the development of functional and regenerative therapies for diverse clinical applications.
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  • 文章类型: Journal Article
    关节软骨是具有非常有限的自我再生能力的无血管组织。创伤或损伤相关缺陷,炎症,或关节软骨的老化可诱发进行性退行性关节疾病,如骨关节炎。对于开发有效的治疗方法以促进关节软骨修复或再生存在显著的临床需求。目前用于修复软骨损伤的治疗方式主要包括基于细胞的治疗,小分子,手术方法,和组织工程。然而,这些方法仍然不能令人满意。随着三维(3D)生物打印技术的出现,组织工程提供了一个机会来修复关节软骨缺损或退化通过有组织的建设,由生物材料组成的生物结构,软骨细胞,和生物活性因子。生物打印的软骨样结构可以模拟天然的关节软骨,与传统方法相反,通过允许软骨细胞分布的良好控制和生物力学和生化特性的高精度调制。这篇综述集中在各种水凝胶,包括天然和合成水凝胶,以及他们目前在软骨组织工程3D生物打印中作为生物墨水的发展。此外,还讨论了这些水凝胶在软骨组织工程应用中的挑战和前景。
    Articular cartilage is an avascular tissue with very limited capacity of self-regeneration. Trauma or injury-related defects, inflammation, or aging in articular cartilage can induce progressive degenerative joint diseases such as osteoarthritis. There are significant clinical demands for the development of effective therapeutic approaches to promote articular cartilage repair or regeneration. The current treatment modalities used for the repair of cartilage lesions mainly include cell-based therapy, small molecules, surgical approaches, and tissue engineering. However, these approaches remain unsatisfactory. With the advent of three-dimensional (3D) bioprinting technology, tissue engineering provides an opportunity to repair articular cartilage defects or degeneration through the construction of organized, living structures composed of biomaterials, chondrogenic cells, and bioactive factors. The bioprinted cartilage-like structures can mimic native articular cartilage, as opposed to traditional approaches, by allowing excellent control of chondrogenic cell distribution and the modulation of biomechanical and biochemical properties with high precision. This review focuses on various hydrogels, including natural and synthetic hydrogels, and their current developments as bioinks in 3D bioprinting for cartilage tissue engineering. In addition, the challenges and prospects of these hydrogels in cartilage tissue engineering applications are also discussed.
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  • 文章类型: Journal Article
    导电/绝缘油墨已经受到广泛关注,用于制造各种增材制造技术。然而,目前的油墨通常表现出较差的生物相容性,并且在生理条件下面临电导率和机械刚度之间的权衡。这里,提出了基于二维材料的导电/绝缘生物墨水。导电生物墨水,石墨烯(GR)-聚(乳酸-乙醇酸)(PLGA),通过将导电GR引入可降解的聚合物基质中来制备,PLGA,而绝缘的生物墨水,氮化硼(BN)-PLGA,通过添加绝缘BN合成。通过优化材料比,这项工作实现了对生物墨水的机电特性的精确控制,从而能够根据具体要求进行导电网络的柔性构造。此外,这些生物墨水与3D打印等各种制造技术兼容,静电纺丝,旋涂,和注塑成型,拓展其在生物医学领域的应用范围。总的来说,结果表明,这些导电/绝缘生物墨水提供了改进的机械,电子,和各种新兴生物医学应用的生物学特性。
    Conducting/insulating inks have received significant attention for the fabrication of a wide range of additive manufacturing technology. However, current inks often demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. Here, conductive/insulating bioinks based on two-dimensional materials are proposed. The conductive bioink, graphene (GR)-poly(lactic-co-glycolic acid) (PLGA), is prepared by introducing conductive GR into a degradable polymer matrix, PLGA, while the insulating bioink, boron nitride (BN)-PLGA, is synthesized by adding insulating BN. By optimizing the material ratios, this work achieves precise control of the electromechanical properties of the bioinks, thereby enabling the flexible construction of conductive networks according to specific requirements. Furthermore, these bioinks are compatible with a variety of manufacturing technologies such as 3D printing, electrospinning, spin coating, and injection molding, expanding their application range in the biomedical field. Overall, the results suggest that these conducting/insulating bioinks offer improved mechanical, electronic, and biological properties for various emerging biomedical applications.
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  • 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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