Bio-Design and Manufacturing最新文献

Jetting-based bioprinting facilitates contactless drop-on-demand deposition of subnanoliter droplets at well-defined positions to control the spatial arrangement of cells, growth factors, drugs, and biomaterials in a highly automated layer-by-layer fabrication approach. Due to its immense versatility, jetting-based bioprinting has been used for various applications, including tissue engineering and regenerative medicine, wound healing, and drug development. A lack of in-depth understanding exists in the processes that occur during jetting-based bioprinting. This review paper will comprehensively discuss the physical considerations for bioinks and printing conditions used in jetting-based bioprinting. We first present an overview of different jetting-based bioprinting techniques such as inkjet bioprinting, laser-induced forward transfer bioprinting, electrohydrodynamic jet bioprinting, acoustic bioprinting and microvalve bioprinting. Next, we provide an in-depth discussion of various considerations for bioink formulation relating to cell deposition, print chamber design, droplet formation and droplet impact. Finally, we highlight recent accomplishments in jetting-based bioprinting. We present the advantages and challenges of each method, discuss considerations relating to cell viability and protein stability, and conclude by providing insights into future directions of jetting-based bioprinting.

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理想的钛基关节植入物应避免力屏蔽, 且具有良好的生物活性和抗感染性能。为满足这些要求, 研究人员以低弹性模量合金Ti–35Nb–2Ta–3Zr为基底, 采用阳极化、沉积和旋涂等方法制备含有生物陶瓷和银离子的功能涂层, 并将其涂覆在TiO₂纳米管 ((80 ± 20) nm 和(150 ± 40) nm) 表面。研究了生物陶瓷 (nano-β-TCP, micro-HA, meso-CaSiO₃) 和Ag纳米颗粒 ((50 ± 20) nm) 对纳米管的抗菌活性、摩擦、腐蚀和早期体外成骨行为的影响。摩擦和腐蚀结果表明, 磨损率和腐蚀速率与纳米管表面形貌密切相关。由于粘着磨损和磨粒磨损, 生物陶瓷micro-HA 表现出优异的耐磨性, 磨损率为(1.26 ± 0.06)×10^–3 mm³/(N m)。生物陶瓷meso-CaSiO₃显示出良好的细胞粘附、增殖能力和碱性磷酸酶活性。含有纳米银的涂层具有良好的抗菌活性, 对大肠杆菌的抗菌率 ≥ 89.5%。研究结果表明, 该功能涂层具有加速成骨的潜力。

Sweat loss monitoring is important for understanding the body’s thermoregulation and hydration status, as well as for comprehensive sweat analysis. Despite recent advances, developing a low-cost, scalable, and universal method for the fabrication of colorimetric microfluidics designed for sweat loss monitoring remains challenging. In this study, we propose a novel laser-engraved surface roughening strategy for various flexible substrates. This process permits the construction of microchannels that show distinct structural reflectance changes before and after sweat filling. By leveraging these unique optical properties, we have developed a fully laser-engraved microfluidic device for the quantification of naked-eye sweat loss. This sweat loss sensor is capable of a volume resolution of 0.5 μL and a total volume capacity of 11 μL, and can be customized to meet different performance requirements. Moreover, we report the development of a crosstalk-free dual-mode sweat microfluidic system that integrates an Ag/AgCl chloride sensor and a matching wireless measurement flexible printed circuit board. This integrated system enables the real-time monitoring of colorimetric sweat loss signals and potential ion concentration signals without crosstalk. Finally, we demonstrate the potential practical use of this microfluidic sweat loss sensor and its integrated system for sports medicine via on-body studies.

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Touch-sensitive screens are crucial components of wearable devices. Materials such as reduced graphene oxide (rGO), carbon nanotubes (CNTs), and graphene offer promising solutions for flexible touch-sensitive screens. However, when stacked with flexible substrates to form multilayered capacitive touching sensors, these materials often suffer from substrate delamination in response to deformation; this is due to the materials having different Young’s modulus values. Delamination results in failure to offer accurate touch screen recognition. In this work, we demonstrate an induced charge-based mutual capacitive touching sensor capable of high-precision touch sensing. This is enabled by electron trapping and polarization effects related to mixed-coordinated bonding between copper nanoparticles and vertically grown graphene nanosheets. Here, we used an electron cyclotron resonance system to directly fabricate graphene–metal nanofilms (GMNFs) using carbon and copper, which are firmly adhered to flexible substrates. After being subjected to 3000 bending actions, we observed almost no change in touch sensitivity. The screen interaction system, which has a signal-to-noise ratio of 41.16 dB and resolution of 650 dpi, was tested using a handwritten Chinese character recognition trial and achieved an accuracy of 94.82%. Taken together, these results show the promise of touch-sensitive screens that use directly fabricated GMNFs for wearable devices.

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As the main component of wearable electronic equipment, flexible pressure sensors have attracted wide attention due to their excellent sensitivity and their promise with respect to applications in health monitoring, electronic skin, and human–computer interactions. However, it remains a significant challenge to achieve epidermal sensing over a wide sensing range, with short response/recovery time and featuring seamless conformability to the skin simultaneously. This is critical since the capture of minute electrophysiological signals is important for health care applications. In this paper, we report the preparation of a nacre-like MXene/sodium carboxymethyl cellulose (CMC) nanocomposite film with a “brick-and-mortar” interior structure using a vacuum-induced self-assembly strategy. The synergistic behavior of the MXene “brick” and flexible CMC “mortar” contributes to attenuating interlamellar self-stacking and creates numerous variable conductive pathways on the sensing film. This resulted in a high sensitivity over a broad pressure range (i.e., 0.03–22.37 kPa: 162.13 kPa⁻¹; 22.37–135.71 kPa: 127.88 kPa⁻¹; 135.71–286.49 kPa: 100.58 kPa⁻¹). This sensor also has a low detection limit (0.85 Pa), short response/recovery time (8.58 ms/34.34 ms), and good stability (2000 cycles). Furthermore, we deployed pressure sensors to distinguish among tiny particles, various physiological signals of the human body, space arrays, robot motion monitoring, and other related applications to demonstrate their feasibility for a variety of health and motion monitoring use cases.

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监测神经元的电生理活动和血液中的钙离子可以帮助人们更好地了解与疾病相 关的神经系统回路。然而，当前原位钙离子监测工具很少，且大多集成度低、灵 敏度有限。本文提出一种集成原位Ag/AgCl 参比电极（ISA/ARE）的植入式探针， 该探针可以监测动作电位（AP）和Ca²⁺浓度。实验结果表明，Ca²⁺传感器的灵敏 度可达100.7 mV/decade，其在干扰物实验中呈现良好的选择性。本研究通过铂 黑修饰的12 个电生理电极记录到了神经元的AP，而当将CaCl₂ 溶液重复微注射 到大脑的CA1 区域时，Ca²⁺传感器则观察到神经元的可逆电位变化。上述结果 表明，该探针能够满足电生理信号和离子浓度同步监测的需求，加深人们对神经 回路的理解，促进脑科学的发展。

High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization, as the spatial scale of some pathologic signals is at the submillimeter or micrometer level. This entails connecting hundreds or thousands of electrode wires on a limited surface. This study reported a class of flexible, ultrathin, high-density electrocorticogram (ECoG) electrode arrays. The challenge of a large number of wiring arrangements was overcome by a laminated structure design and processing technology improvement. The flexible, ultrathin, high-density ECoG electrode array was conformably attached to the cortex for reliable, high spatial resolution electrophysiologic recordings. The minimum spacing between electrodes was 15 μm, comparable to the diameter of a single neuron. Eight hundred electrodes were prepared with an electrode density of 4444 mm⁻². In focal epilepsy surgery, the flexible, high-density, laminated ECoG electrode array with 36 electrodes was applied to collect epileptic spike waves in rabbits, improving the positioning accuracy of epilepsy lesions from the centimeter to the submillimeter level. The flexible, high-density, laminated ECoG electrode array has potential clinical applications in intractable epilepsy and other neurologic diseases requiring high-precision electroencephalogram acquisition.

Oxygen (O₂)-sensing matrices are promising tools for the live monitoring of extracellular O₂ consumption levels in long-term cell cultures. In this study, ratiometric O₂-sensing membranes were prepared by electrospinning, an easy, low-cost, scalable, and robust method for fabricating nanofibers. Poly(ε-caprolactone) and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride, which was used as the O₂-sensing probe, and rhodamine B isothiocyanate, which was used as the reference dye. The functionalized scaffolds were morphologically characterized by scanning electron microscopy, and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy, thermogravimetric analysis, and water contact angle measurement. The sensing capabilities were investigated by confocal laser scanning microscopy, performing photobleaching, reversibility, and calibration curve studies toward different dissolved O₂ (DO) concentrations. Electrospun sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5 to 20% and good stability under ratiometric imaging. In addition, the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines, namely metastatic melanoma cell line SK-MEL2, breast cancer cell line MCF-7, and pancreatic ductal adenocarcinoma cell line Panc-1, thus recreating a suitable biological environment in vitro. These O₂-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O₂ content during drug testing/validation and tissue regeneration processes.

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Three-dimensional (3D) printing has attracted increasing research interest as an emerging manufacturing technology for developing sophisticated and exquisite architecture through hierarchical printing. It has also been employed in various advanced industrial areas. The development of intelligent biomedical engineering has raised the requirements for 3D printing, such as flexible manufacturing processes and technologies, biocompatible constituents, and alternative bioproducts. However, state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields, thus severely limiting applications demanding biocompatibility and biodegradability. In this regard, peptide architectonics, which are self-assembled by programmed amino acid sequences that can be flexibly functionalized, have shown promising potential as bioinspired inks for 3D printing. Therefore, the combination of 3D printing and peptide self-assembly potentially opens up an alternative avenue of 3D bioprinting for diverse advanced applications. Israel, a small but innovative nation, has significantly contributed to 3D bioprinting in terms of scientific studies, marketization, and peptide architectonics, including modulations and applications, and ranks as a leading area in the 3D bioprinting field. This review summarizes the recent progress in 3D bioprinting in Israel, focusing on scientific studies on printable components, soft devices, and tissue engineering. This paper further delves into the manufacture of industrial products, such as artificial meats and bioinspired supramolecular architectures, and the mechanisms, physicochemical properties, and applications of peptide self-assembly. Undoubtedly, Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.

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Tissue engineering has been striving toward designing and producing natural and functional human tissues. Cells are the fundamental building blocks of tissues. Compared with traditional two-dimensional cultured cells, cell spheres are three-dimensional (3D) structures that can naturally form complex cell–cell and cell–matrix interactions. This structure is close to the natural environment of cells in living organisms. In addition to being used in disease modeling and drug screening, spheroids have significant potential in tissue regeneration. The 3D bioprinting is an advanced biofabrication technique. It accurately deposits bioinks into predesigned 3D shapes to create complex tissue structures. Although 3D bioprinting is efficient, the time required for cells to develop into complex tissue structures can be lengthy. The 3D bioprinting of spheroids significantly reduces the time required for their development into large tissues/organs during later cultivation stages by printing them with high cell density. Combining spheroid fabrication and bioprinting technology should provide a new solution to many problems in regenerative medicine. This paper systematically elaborates and analyzes the spheroid fabrication methods and 3D bioprinting strategies by introducing spheroids as building blocks. Finally, we present the primary challenges faced by spheroid fabrication and 3D bioprinting with future requirements and some recommendations.

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