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 pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-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.

3D细胞打印技术由于能够在预定的空间位置精确地对活细胞进行图案化而备受关注，已成为吸引人的生物加工平台。在皮肤组织工程中，主要的挑战是寻求一种合适的生物墨水来源，其能够支持和刺激用于组织发育的印刷细胞。然而，当前用于皮肤印刷的生物油墨依赖于均质的生物材料，其具有一些缺点，例如机械性能不足和微环境的概括。在这项研究中，我们调查了基于皮肤的细胞外基质（S-dECM）生物墨水对基于3D细胞打印的皮肤组织工程的能力。S-dECM首次配制为可印刷材料，并保留了皮肤的主要ECM成分以及有利的生长因子和细胞因子。这种生物墨水用于打印全厚度的3D人体皮肤模型。使用S-dECM生物墨水的成熟3D细胞打印皮肤组织在最小收缩的情况下稳定下来，而胶原蛋白皮肤组织在此过程中明显收缩体外组织培养。来自我们bioink的这种物理稳定性和特定于组织的微环境改善了表皮组织，真皮ECM分泌和屏障功能。我们进一步使用了这种生物墨水来打印能够促进体内伤口愈合的3D预血管化皮肤贴剂。体内结果显示，载有内皮祖细胞（EPC）的3D打印皮肤贴片以及来自脂肪的干细胞（ASC）加速伤口闭合，再上皮形成和新血管形成以及血流。我们预想，本文的结果可以为迈向下一代生物墨水制造提供有见地的步骤。