1,720,974 research outputs found
Inkjet Printing of a 3D Microstructured Human Skin Equivalent
No full textNeeds for highly mimetic human skin models are becoming larger than before these days as animal testing in the cosmetics field is gradually
being banned in many countries starting from European Union since 2013. Fabrication of artificial human skin equivalents with the increased
representativeness is required to substitute the gap of the conventional animal testing. The skin is the largest organ of the body with the
structural and functional complexity. Microstructures of dermis which help sustaining dermal-epidermal junction are the one of the key features
among the existing complexities in skin such as appendages, vasculatures, immune cells, and pigment. However, conventional skin equivalents
are made simply by stacking dermis and epidermis layers, lacking the detailed microstructures of human skin. Here, we present a 3D human
skin model with microstructured dermis. The piezo-type inkjet printer enabled the controlled displacement and density of Type I collagen,
dermal fibroblasts, and epidermal keratinocytes with high accuracy. We found that the degree of collagen contraction varies with the density of
printed dermal fibroblasts. We used this phenomena to form papillary microstructures in the dermal layer. Various forms of microstructures
were fabricated by changing local density of dermal fibroblasts or shapes of patterns. Epidermal keratinocytes were also inkjet printed as a
densely packed monolayer within a controlled region preventing slipping away from the surface of the dermal collagen area. We believe that
the inkjet-bioprinted 3D human skin equivalents with microstructures will play a critical role as a bridge between in vitro human models and in
vivo tissues by replacing animal testing.1
Tattoo sticker-like 3D flexible Cell sheet transfer platform based on Spontaneous Interfacial cell migration
No full textCell sheet technology is a remarkable option to avoid the limitations of conventional tissue engineering techniques. Cell sheets are maintained intact cell-cell junction and extracellular matrix proteins by a protease-free cell harvesting and scaffold-free cell delivery system. Most cell sheet studies use a thermo-responsive cell harvesting system. However, here, we introduce another unique and flexible cell delivery platform. Our cell sheet transferring system uses a parylene flexible thin-film cell transfer carrier to culture and transfer cell sheet. With the support of the parylene film, cell sheets can be simply designed in any shape and size, and easily transferred to the target surface while maintaining the original cell sheet design and even single-cell spreading morphologies like tattoo stickers. Using our delivery platform, each cell could maintain its cytoskeletal structures after transfer to the target. Different from other cell sheet harvesting methods, a parylene film cell delivery system is based on spontaneous interfacial cell migration without any artificial triggers such as lowering the temperature, electrical stimuli, or PH change. In addition, the cell sheets could be easily stacked in heterotypic multilayered forms and applied to a wound site, confirming its potential application for in situ patient-specific wound patch transplantation. This easy-to-use cell delivery platform can contribute to the wider therapeutic application of cell sheet technology and our deeper understanding of cellular behaviors with interfacial migratory capability.1
Inkjet-bioprinted 3D Microstructured Human Skin Equivalent
No full textTissue-engineered human skin equivalents which can represent the original human skin with a physiological relevance are in high-demand to replace the conventional animal testing in the cosmetics field and also to promote regeneration of large-area skin defects. In human skin, there are papillary microarchitectures in the dermo-epidermal junction, which serve both structural and functional roles as for they provide a strengthened mechanical anchoring and an active interaction between the dermis and the epidermis. However, conventional skin equivalents have been made simply by stacking dermis and epidermis layers in a planar manner, lacking the detailed microstructures of the native human skin. Here, we present a bioprinted human skin model with 3D microstructured dermis. The piezo-type inkjet printer enables the fabrication of cell patterns with a dermal fibroblast-laden collagen ink with high accuracy. As fibroblasts are widely known as they rearrange and reorganize the surrounding extracellular matrices by adhering and anchoring within them, we use this phenomena to form papillary microstructures in the dermal layer. By changing local density of dermal fibroblasts or by applying various shapes of cell patterns using inkjet cell printing, we are able to induce controlled 3D microstructures from printed fibroblasts as intended. Epidermal keratinocytes were then inkjet-printed onto the 3D microstructured dermis to form a densely packed monolayer. We believe that the inkjet-bioprinted 3D microstructured human skin equivalents will provide an enhanced physiological connection between in vitro and in vivo.2
3D-Printed Airway Model as a Tool for Studying SARS-CoV-2 Infection and Antiviral Therapeutics
No full textThe outbreak of the SARS-CoV-2 has caused the infection of numerous people, resulting in the majority of them suffering from respiratory disease. There is a need for an in vitro lung model in which antiviral drugs can be tested reliably and quickly against the novel coronavirus. A physiologically relevant respiratory model provides a drug screening platform to study SARS-CoV-2 infection. We recapitulated the multi-layered human airway structure consisting of pulmonary endothelium, extracellular matrix, and airway epithelium through automated inkjet and microextrusion bioprinting. The 3D microarchitecture exhibits cell-cell junction and mucus secretion which are the major respiratory barrier to viral infection, and also expressed ACE2 and TMPRSS2 which are known to be involved in SARS-CoV-2 cell entry. We investigated the response following infection with SARS-CoV-2 in the 3D airway model. The infection induced cytopathic effect and barrier destruction in the model over time. Virus replication was effectively inhibited when an infected 3D airway model was treated with remdesivir and molnupiravir, approved for the treatment of COVID-19. Then the EC50 was determined for each drug in the model. The 3D-printed airway model can be used as a tool for studying viral infection and validating the efficacy of therapeutics against other respiratory infection viruses as well as SARS-CoV-2.1
All-Printed 3D Human Skin Equivalents for Wound Healing
No full textFabrication of human skin equivalents with a physiological relevance to the native human skin is becoming more necessary to displace the conventional animal testing in the cosmetics field or the autologous transplantation for medical treatment. Here, we present all-printed full-thickness 3D human skin equivalents as an end product and introduce the key roles of precise inkjet cell patterning in the tissue fabrication and wound healing.1
Heterogeneous nuclear ribonucleoprotein A1 regulates rhythmic synthesis of mouse Nfil3 protein via IRES-mediated translation.
Get PDFNuclear factor, interleukin 3, regulated (Nfil3, also known as E4 Promoter-Binding Protein 4 (E4BP4)) protein is a transcription factor that binds to DNA and generally represses target gene expression. In the circadian clock system, Nfil3 binds to a D-box element residing in the promoter of clock genes and contributes to their robust oscillation. Here, we show that the 5'-untranslated region (5'-UTR) of Nfil3 mRNA contains an internal ribosome entry site (IRES) and that IRES-mediated translation occurs in a phase-dependent manner. We demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) binds to a specific region of Nfil3 mRNA and regulates IRES-mediated translation. Knockdown of hnRNP A1 almost completely abolishes protein oscillation without affecting mRNA oscillation. Moreover, we observe that intracellular calcium levels, which are closely related to bone formation, depend on Nfil3 levels in osteoblast cell lines. We suggest that the 5'-UTR mediated cap-independent translation of Nfil3 mRNA contributes to the rhythmic expression of Nfil3 by interacting with the RNA binding protein hnRNP A1. These data provide new evidence that the posttranscriptional regulation of clock gene expression is important during bone metabolism.1131Ysciescopu
Inkjet-Spray Hybrid Printing for Large-Scale Fabrication of Multi-Layered Hydrogel Structure
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