Three-dimensional bioprinting of a full-thickness functional skin model using acellular dermal matrix and gelatin methacrylamide bioink
Three-dimensional bioprinting of a full-thickness functional skin model using acellular dermal matrix and gelatin methacrylamide bioink
复制标题
使用脱细胞真皮基质和明胶甲基丙烯酰胺生物墨水对全层功能性皮肤模型进行三维生物打印
DOI：
10.1016/j.actbio.2021.07.012
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发表时间：
2021-08-14
影响因子：
9.7
通讯作者：
Wang, Xingang
中科院分区：
文献类型：
--
作者：
Jin, Ronghua;Cui, Yuecheng;Wang, Xingang
全层皮肤缺损的治疗在临床实践中仍然是一个重大的挑战。三维生物打印技术为制造皮肤替代品提供了一种很有前途的方法。然而，有必要确定既具有足够的机械性能又具有理想的生物相容性的生物墨水。在这项研究中，我们成功地制备了脱细胞真皮基质（ADM）和明胶甲基丙烯酰胺（GelMA）生物墨水。结果表明，ADM保留了皮肤的主要细胞外基质（ECM）成分，GelMA具有可调节的力学性能。两种具有剪切减薄特性的生物墨水都适合3D生物打印，GelMA生物墨水具有较高的打印适性。此外，结果表明，20%的GelMA具有足够的机械性能，适合工程表皮，1.5%的ADM和10%的GelMA具有相对较好的细胞相容性。在这里，我们提出了一种新的3D结构来模拟天然全层皮肤，其中包括20%的GelMA， HaCaTs作为表皮层，1.5%的ADM，成纤维细胞作为真皮层，10%的GelMA网格，人脐静脉内皮细胞（HUVECs）作为血管网络和框架。我们证明了这种3D生物打印功能皮肤模型（FSM）不仅可以促进细胞活力和增殖，还可以支持表皮的体外重建。在体内移植时，FSM可以维持细胞活力至少1周。此外，FSM促进创面愈合和再上皮形成，刺激真皮ECM分泌和血管生成，改善创面愈合质量。FSM可能为未来的临床应用提供可行的功能性皮肤替代品。我们提出了一种新的3D结构来模拟天然全层皮肤，其中包括20%的GelMA与HaCaTs作为表皮层，1.5%的ADM与成纤维细胞作为真皮层，10%的GelMA网格与HUVECs作为血管网络。它既能维持湿润的微环境和屏障功能，又能重塑皮肤的自然微环境，促进细胞的活力和增殖。这可能为未来的临床应用提供可行的功能性皮肤替代品。(c) 2021 Acta Materialia Inc.Elsevier Ltd.出版。版权所有。
Treatment of full-thickness skin defects still presents a significant challenge in clinical practice. Threedimensional (3D) bioprinting technique offers a promising approach for fabricating skin substitutes. However, it is necessary to identify bioinks that have both sufficient mechanical properties and desirable biocompatibilities. In this study, we successfully fabricated acellular dermal matrix (ADM) and gelatin methacrylamide (GelMA) bioinks. The results demonstrated that ADM preserved the main extracellular matrix (ECM) components of the skin and GelMA had tunable mechanical properties. Both bioinks with shear-thinning properties were suitable for 3D bioprinting and GelMA bioink exhibited high printability. Additionally, the results revealed that 20% GelMA with sufficient mechanical properties was suitable to engineer epidermis, 1.5% ADM and 10% GelMA displayed relatively good cytocompatibilities. Here, we proposed a new 3D structure to simulate natural full-thickness skin, which included 20% GelMA with HaCaTs as an epidermal layer, 1.5% ADM with fibroblasts as the dermis, and 10% GelMA mesh with human umbilical vein endothelial cells (HUVECs) as the vascular network and framework. We demonstrated that this 3D bioprinting functional skin model (FSM) could not only promote cell viability and proliferation, but also support epidermis reconstruction in vitro . When transplanted in vivo , the FSM could maintain cell viability for at least 1 week. Furthermore, the FSM promoted wound healing and re-epithelization, stimulated dermal ECM secretion and angiogenesis, and improved wound healing quality. The FSM may provide viable functional skin substitutes for future clinical applications. Statement of significance We propose a new 3D structure to simulate natural full-thickness skin, which included 20% GelMA with HaCaTs as an epidermal layer, 1.5% ADM with fibroblasts as the dermis, and 10% GelMA mesh with HUVECs as the vascular network. It could not only maintain a moist microenvironment and barrier function, but also recreate the natural skin microenvironment to promote cell viability and proliferation. This may provide viable functional skin substitutes for future clinical applications. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.