Rapid printing of bio-inspired 3D tissue constructs for skin regeneration
Rapid printing of bio-inspired 3D tissue constructs for skin regeneration
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快速打印用于皮肤再生的仿生 3D 组织结构
DOI：
10.1016/j.biomaterials.2020.120287
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发表时间：
2020-11-01
期刊：
影响因子：
14
通讯作者：
Ouyang, Hongwei
中科院分区：
文献类型：
--
作者：
Zhou, Feifei;Hong, Yi;Ouyang, Hongwei
对于现有的生物打印技术来说，制造适合植入的器官仍然是一个挑战，主要是因为无法概括器官的复杂解剖结构、机械性能和生物功能。此外，未能创造出具有相互连接的微通道的3D结构，以用于远程大规模运输，这限制了3D打印技术的临床应用。在这里，开发了一种新的方法来打印功能性活体皮肤(FLS)，使用新设计的仿生生物墨水(GelMA/HA-NB/LAP)和基于数字光处理(DLP)的3D打印技术。FLS具有相互连接的微通道，促进细胞迁移、增殖和新组织形成。由甲基丙烯酸明胶(GelMA)、N-(2-氨基乙基)4(4(羟甲基)-2-甲氧基-5-亚硝基苯氧基)丁酰胺(NB)连接透明质酸(HA-NB)和光引发剂苯基-2，4，6-三甲基苯甲酰基膦酸锂(LAP)组成的GelMA/HA-NB/LAP生物墨水。该生物墨水具有快速的凝胶动力学、可调的力学性能、良好的生物相容性和组织粘附性。基于DLP的3D打印技术提供了一种快速定位具有高细胞活性的人皮肤成纤维细胞(HSF)和人脐静脉内皮细胞(HUVECs)形成FLS的方法。FLS通过模拟自然皮肤的生理结构促进皮肤再生和有效的新生血管，而且由于其强大的机械和生物粘附性，它也可以很容易地操作和植入到创面上。此外，活体研究表明，活体皮肤具有即时防御功能，在促进大型动物皮肤附属物的真皮再生方面具有优越的性能。本研究为今后的临床应用提供了一种快速、批量生产功能活体器官的方法。
It is still a challenge for existing bioprinting technologies to fabricate organs suitable for implantation, mainly due to the inability to recapitulate the organs' complex anatomical structures, mechanical properties, and biological functions. Additionally, the failure to create 3D constructs with interconnected microchannels for longrange mass transportation that limits the clinical applications of 3D printing technologies. Here, a new method was developed to print functional living skin (FLS) using a newly designed biomimetic bioink (GelMA/HA-NB/LAP) and digital light processing (DLP)-based 3D printing technology. The FLS possess interconnected microchannels that facilitates cell migration, proliferation and neo-tissue formation. The GelMA/HA-NB/LAP bioink, composed of gelatin methacrylate (GelMA), N-(2-aminoethyl) 4 (4 (hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide (NB) linked hyaluronic acid (HA-NB) and photo-initiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). The bioink demonstrated its rapid gelation kinetics, tunable mechanical properties, good biocompatibility and tissue adhesion. The DLP-based 3D printing technology provides a rapid method to precisely position clusters of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs) with high cell viability to form FLS. The FLS promotes skin regeneration and efficient neovascularization by mimicking the physiological structure of natural skin, and it can also be easily handled and implanted onto the wound site due to its strong mechanical and bio-adhesive properties. Moreover, in vivo study demonstrated that the living skin exhibited instant defense function and had superior performance in promoting dermal regeneration with skin appendages in large animals. This study provides a rapid and mass production method of functional living organs for future clinical applications.