The liver, the largest gland in the human body, plays a key role in metabolism, bile production, detoxification, and water and electrolyte regulation. The toxins or drugs that the gastrointestinal system absorbs reach the liver first before entering the bloodstream. Liver disease is one of the leading causes of death worldwide. Therefore, an in vitro liver tissue model that reproduces the main functions of the liver can be a reliable platform for investigating liver diseases and developing new drugs. In addition, the limitations in traditional, planar monolayer cell cultures and animal tests for evaluating the toxicity and efficacy of drug candidates can be overcome. Currently, the newly emerging 3D bioprinting technologies have the ability to construct in vitro liver tissue models both in static scaffolds and dynamic liver‐on‐chip manners. This review mainly focuses on the construction and applications of liver tissue models based on 3D bioprinting. Special attention is given to 3D bioprinting strategies and bioinks for constructing liver tissue models including the cell sources and hydrogel selection. In addition, the main advantages and limitations and the major challenges and future perspectives are discussed, paving the way for the next generation of in vitro liver tissue models.
The actuation and energy-harvesting performance of dielectric elastomers are strongly related to their intrinsic electrical and mechanical properties. For future resilient smart transducers, a fast actuation response, efficient energy-harvesting performance, and mechanical robustness are key requirements. In this work, we demonstrate that poly(styrene-butadiene-styrene) (SBS) can be converted into a self-healing dielectric elastomer with high permittivity and low dielectric loss, which can be deformed to large mechanical strains; these are key requirements for actuation and energy-harvesting applications. Using a one-step click reaction at room temperature for 20 min, methyl-3-mercaptopropionate (M3M) was grafted to SBS and reached 95.2% of grafting ratios. The resultant M3M–SBS can be deformed to a high mechanical strain of 1000%, with a relative permittivity of εr = 7.5 and a low tan δ = 0.03. When used in a dielectric actuator, it can provide 9.2% strain at an electric field of 39.5 MV m–1 and can also generate an energy density of 11 mJ g–1 from energy harvesting. After being subjected to mechanical damage, the self-healed elastomer can recover 44% of its breakdown strength during energy harvesting. This work demonstrates a facile route to produce self-healing, high permittivity, and low dielectric loss elastomers for both actuation and energy harvesting, which is applicable to a wide range of diene elastomer systems.
Three-dimensional (3D) embedded printing is emerging as a potential solution for the fabrication of complex biological structures and with ultrasoft biomaterials. For the supporting medium, bulk gels can support a wide range of bioinks with higher printing resolution as well as better finishing surfaces than granular microgel baths. However, the difficulties of regulating the physical properties of existing bulk gel supporting baths limit the further development of this method. This work has developed a bulk gel supporting bath with easily regulable physical properties to facilitate soft-material fabrication. The proposed bath is composed based on the hydrophobic association between a hydrophobically modified hydroxypropylmethyl cellulose (H-HPMC) and Pluronic F-127 (PF-127). Its rheological properties can be easily regulated; in the preprinting stage by varying the relative concentration of components, during printing by changing the temperature, and postprinting by adding additives with strong hydrophobicity or hydrophilicity. This has made the supporting bath not only available for various bioinks with a range of printing windows but also easy to be removed. Also, the removal strategy is independent of printing conditions like temperature and ions, which empowers the bath to hold great potential for the embedded printing of commonly used biomaterials. The adjustable rheological properties of the bath were leveraged to characterize the embedded printing quantitatively, involving the disturbance during the printing, filament cross-sectional shape, printing resolution, continuity, and the coalescence between adjacent filaments. The match between the bioink and the bath was also explored. Furthermore, low-viscosity bioinks (with 0.008–2.4 Pa s viscosity) were patterned into various 3D complex delicate soft structures (with a 0.5–5 kPa compressive modulus). It is believed that such an easily regulable assembled bath could serve as an available tool to support the complex biological structure fabrication and open unique prospects for personalized medicine.
Embedded freeform writing addresses the contradiction between the material printability and biocompatibility for conventional extrusion-based bioprinting. However, the existing embedding mediums have limitations concerning the restricted printing temperature window, compatibility with bioinks or crosslinkers, and difficulties on medium removal. This work demonstrates a new embedding medium to meet the above demands, which composes of hydrophobically modified hydroxypropylmethyl cellulose (H-HPMC) and Pluronic F-127 (PF-127). The adjustable hydrophobic and hydrophilic associations between the components permit tunable thermoresponsive rheological properties, providing a programable printing window. These associations are hardly compromised by additives without strong hydrophilic groups, which means it is compatible with the majority of bioink choices. We use polyethylene glycol 400, a strong hydrophilic polymer, to facilitate easy medium removal. The proposed medium enables freeform writing of the millimetric complex tubular structures with great shape fidelity and cell viability. Moreover, five bioinks with up to five different crosslinking methods are patterned into arbitrary geometries in one single medium, demonstrating its potential in heterogeneous tissue regeneration. Utilizing the rheological properties of the medium, an enhanced adhesion writing method is developed to optimize the structure’s strand-to-strand adhesion. In summary, this versatile embedding medium provides excellent compatibility with multi-crosslinking methods and a tunable printing window, opening new opportunities for heterogeneous tissue regeneration.
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