Three-Dimensional Bioprinting of a Full-Thickness Functional Skin Model Using Acellular Dermal Matrix and Gelatine Methacrylamide Bioink
Three-Dimensional Bioprinting of a Full-Thickness Functional Skin Model Using Acellular Dermal Matrix and Gelatine Methacrylamide Bioink
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DOI：
10.2139/ssrn.3814585
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发表时间：
2021-03
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影响因子：
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通讯作者：
R. Jin;Yuecheng Cui;Haojiao Chen;Zhenzhen Zhang;T. Weng;S. Xia;Meirong Yu;Wei Zhang;J. Shao;Min Yang;Chunmao Han;Xingang Wang
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作者：
R. Jin;Yuecheng Cui;Haojiao Chen;Zhenzhen Zhang;T. Weng;S. Xia;Meirong Yu;Wei Zhang;J. Shao;Min Yang;Chunmao Han;Xingang Wang
全层皮肤缺损的治疗仍然是临床实践中的一个重大挑战。三维（3D）生物打印技术为制造皮肤替代品提供了一种有前途的方法。然而，有必要鉴定具有足够的机械性能和期望的生物相容性两者的生物油墨。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具有可调的机械性能。两种具有剪切稀化特性的生物墨水都适合于3D生物打印，并且GelMA生物墨水表现出高的可打印性。结果表明，20%GelMA具有足够的力学性能，适合于表皮工程，1.5%ADM和10%GelMA具有较好的细胞相容性。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与HaCaTs作为表皮层，1.5%的ADM与成纤维细胞作为真皮，以及10%的GelMA网与人脐静脉内皮细胞（HUVEC）作为血管网络和框架。我们证明了这种3D生物打印功能性皮肤模型（FSM）不仅可以促进细胞活力和增殖，还可以支持体外表皮重建。当移植到体内时，FSM可以保持至少1周的细胞活力。此外，FSM促进伤口愈合和再上皮化，刺激真皮ECM分泌和血管生成，并改善伤口愈合质量。FSM可以为未来的临床应用提供可行的功能性皮肤替代物。
Treatment of full-thickness skin defects still presents a significant challenge in clinical practice. Three-dimensional (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.