1,721,239 research outputs found

    Gao, Ge

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    Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics

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    Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next generation therapeutics and diagnostics. (C) 2017 Elsevier Ltd. All rights reserved.11Nsciescopu

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Characterization and Validation of Brain and Blood Vessel-derived Extracellular Matrix Bioinks for Recapitulating Human Blood-Brain Barrier in vitro

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    Globally, neurodegenerative diseases, such as neuroinflammation-associated Alzheimer’s disease and Parkinson’s disease, have affected the health and quality of life of many people. The major regulator of neuroinflammation is the blood-brain barrier (BBB), which controls the molecular transport from brain vasculature to the central nervous system. Since the BBB is a complicated structure consisting of various cell types, animal models are difficult to use for in-depth mechanistic studies in neuroinflammation. Therefore, it is necessary to recapitulate the tissue-specific intrinsic function and pathophysiology of the human BBB in vitro. Previous researches demonstrated that decellularized extracellular matrix (dECM), derived from the target tissue, has advantage in providing tissue specific micro-environmental cues. In this study, we conducted characterization and functional validation of brain-derived dECM (BdECM) and blood vessel-derived dECM (VdECM) for developing human BBB model in vitro. BdECM and VdECM were obtained by decellularization process of porcine brain and aorta tissues, respectively. Briefly, the external blood of chopped tissues was removed with DW, followed by the treatment of sodium dodecyl sulfate (SDS), DNase, Triton-X 100, and peracetic acid. As a final step, the residual detergent was removed with PBS and DW. To validate the process, DNA and glycosaminoglycans (GAGs) quantification were conducted. To further investigate the preserved ECM components, proteomic analysis using LC-MS/MS was conducted. Finally, to validate the cell viability and proliferation and protein expression in BdECM and VdECM, human brain microvascular endothelial cells (HBMECs) and human brain vascular pericytes (HBVPs) were encapsulated in dECM. LIVD/DEAD assay and CCK test and immunofluorescence staining against PDGFR-β and VE-Cadherin were carried out. As a result, biochemical assay of BdECM and VdECM validated reduction of DNA content (25.90 ng/mg and 59.03 ng/mg) and preservation of GAGs (84.7% and 73.0% of native tissue). Proteomic analysis revealed that the main components preserved in BdECM are collagen and laminin, which is major constituent of basement membrane of BBB. On the other hand, the major components of VdECM are vimentin and tubulin, which regulate endothelial sprouting. Furthermore, over 95% cell viability and higher proliferation than collagen in BdECM and VdECM were verified. Finally, corresponding to the result of proteomic analysis, endothelial sprouting-like structure was observed in VdECM. Later, this study will be the basis for developing an in vitro platform for BBB to investigate the mechanism of neuroinflammation.1

    Direct 3D cell-printing of human skin with functional transwell system

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    Three-dimensional (3D) cell-printing has been emerging as a promising technology with which to build up human skin models by enabling rapid and versatile design. Despite the technological advances, challenges remain in the development of fully functional models that recapitulate complexities in the native tissue. Moreover, although several approaches have been explored for the development of biomimetic human skin models, the present skin models based on multistep fabrication methods using polydimethylsiloxane chips and commercial transwell inserts could be tackled by leveraging 3D cell-printing technology. In this paper, we present a new 3D cell-printing strategy for engineering a 3D human skin model with a functional transwell system in a single-step process. A hybrid 3D cell-printing system was developed, allowing for the use of extrusion and inkjet modules at the same time. We began by revealing the significance of each module in engineering human skin models; by using the extrusion-dispensing module, we engineered a collagen-based construct with polycaprolactone (PCL) mesh that prevented the contraction of collagen during tissue maturation; the inkjet-based dispensing module was used to uniformly distribute keratinocytes. Taking these features together, we engineered a human skin model with a functional transwell system; the transwell system and fibroblast-populated dermis were consecutively fabricated by using the extrusion modules. Following this process, keratinocytes were uniformly distributed onto the engineered dermis by the inkjet module. Our transwell system indicates a supportive 3D construct composed of PCL, enabling the maturation of a skin model without the aid of commercial transwell inserts. This skin model revealed favorable biological characteristics that included a stabilized fibroblast-stretched dermis and stratified epidermis layers after 14 days. It was also observed that a 50 times reduction in cost was achieved and 10 times less medium was used than in a conventional culture. Collectively, because this single-step process opens up chances for versatile designs, we envision that our cell-printing strategy could provide an attractive platform in engineering various human skin models.1120sciescopu
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