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3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: A step towards advanced skin tissue engineering

机译:3D体外稳定皮肤模型的细胞印刷和体内预血管化皮肤贴片使用组织特异性细胞外基质Bioink:迈向先进的皮肤组织工程一步

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摘要

3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment. In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D prevascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPC5)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing. (C) 2018 Elsevier Ltd. All rights reserved.
机译:3D细胞印刷技术已经受到焦点,作为一种吸引人的生物破坏平台,因为它能够精确地在预定的空间位置进行拟定活细胞。在皮肤组织工程中,一个主要的致命挑战是寻求能够支持和刺激打印细胞的合适的生物链来源以进行组织发育。然而,目前用于皮肤印刷的生物链依赖于均匀生物材料,这具有几种缺点,例如机械性能不足和微环境的概括。在这项研究中,我们研究了皮肤衍生的细胞外基质(S-DECM)生物链接用于3D细胞印刷的皮肤组织工程的能力。 S-DECM首次配制为可打印材料并保留皮肤的主要ECM组成以及良好的生长因子和细胞因子。该生物链用于打印全厚度3D人体皮肤模型。使用S-DECM生物链接的成熟的3D细胞印刷的皮肤组织稳定,最小收缩,而基于胶原的皮肤组织在体外组织培养期间显着收缩。这种物理稳定和来自我们的生物链的细胞特异性微环境改善表皮组织,皮肤ECM分泌和屏障功能。我们进一步利用这种生物链接到印刷3D,其血糖化皮肤贴片能够在体内伤口愈合中促进。在体内结果表明,内皮祖细胞(EPC5) - 含有脂肪衍生的干细胞(ASCS)的3D印刷皮肤贴片加速伤口闭合,重新上皮,和新血管。我们设想本文的结果可以为生物链接制造的下一代来源提供富有洞察力的步骤。 (c)2018年elestvier有限公司保留所有权利。

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