Human-scale tissues with patterned vascular networks by additive manufacturing of sacrificial sugar-protein composites
Human-scale tissues with patterned vascular networks by additive manufacturing of sacrificial sugar-protein composites
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DOI：
10.1016/j.actbio.2020.06.012
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发表时间：
2020-09-01
影响因子：
9.7
通讯作者：
Dixon, James E.
中科院分区：
文献类型：
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作者：
Eltaher, Hoda M.;Abukunna, Fatima E.;Dixon, James E.
通过提供营养和去除废物来对抗坏死，这是工程化大型三维（3D）组织的主要挑战。先前的出色工作使用3D打印，将碳水化合物玻璃作为细胞相容性牺牲模板，以创建具有血管网络的复杂工程组织（米勒等人，2012，Nature Materials）。这种材料的脆弱性加上创建高分辨率结构所需的技术复杂性，使我们创建了一种灵活的糖-蛋白质复合材料，称为明胶-蔗糖基质（GSM），以实现更坚固和适用的材料。在这里，我们开发了一种低范围（25-37摄氏度）的温度敏感配方，可以在3D打印过程中以微米分辨率特征进行模塑或铸造，以生产形成牺牲容器的复杂柔性细丝网络。使用温度敏感性，我们可以控制长丝变性，这意味着GSM可以与各种基质和交联策略一起使用。此外，通过将生物相容性交联剂直接掺入GSM中，我们可以产生薄的内皮化血管壁并产生含有多种基质和细胞类型的图案化组织。我们还证明了灌注的血管通道维持包括原代人类细胞在内的多种细胞类型的代谢功能。重要的是，我们能够构建血管化的人类鼻子，否则这些鼻子就会坏死。我们的材料现在可以用于再生医学应用，创造人体规模的组织。重要性声明真实的和工程化的组织需要大量运输，交换营养和氧气，因此需要血管化来保持活力和抑制坏死。基本的血管网络必须包括在工程组织内在。然而，直到最近，这在具有组织样细胞密度的生理学大小的构建体中还无法实现。牺牲模塑是一种替代方法，其中创建刚性网格的细丝网络以防止随后的基质进入。我们的研究描述了一种生物相容的牺牲糖蛋白制剂; GSM，由廉价和易得的生物级材料的混合物制成。GSM可以浇铸/模制或生物打印为牺牲丝，其可以温度敏感地快速溶解在水性环境中。GSM材料可用于工程化可行的和血管化的人类规模的组织，用于再生医学应用。(C)2020 Acta Materialia Inc.爱思唯尔有限公司出版
Combating necrosis, by supplying nutrients and removing waste, presents the major challenge for engineering large three-dimensional (3D) tissues. Previous elegant work used 3D printing with carbohydrate glass as a cytocompatible sacrificial template to create complex engineered tissues with vascular networks (Miller et al. 2012, Nature Materials). The fragile nature of this material compounded with the technical complexity needed to create high-resolution structures led us to create a flexible sugar-protein composite, termed Gelatin-sucrose matrix (GSM), to achieve a more robust and applicable material. Here we developed a low-range (25-37 degrees C) temperature sensitive formulation that can be moulded with micron-resolution features or cast during 3D printing to produce complex flexible filament networks forming sacrificial vessels. Using the temperature-sensitivity, we could control filament degeneration meaning GSM can be used with a variety of matrices and crosslinking strategies. Furthermore by incorporation of biocompatible crosslinkers into GSM directly, we could create thin endothelialized vessel walls and generate patterned tissues containing multiple matrices and cell-types. We also demonstrated that perfused vascular channels sustain metabolic function of a variety of cell-types including primary human cells. Importantly, we were able to construct vascularized human noses which otherwise would have been necrotic. Our material can now be exploited to create human-scale tissues for regenerative medicine applications.Statement of SignificanceAuthentic and engineered tissues have demands for mass transport, exchanging nutrients and oxygen, and therefore require vascularization to retain viability and inhibit necrosis. Basic vascular networks must be included within engineered tissues intrinsically. Yet, this has been unachievable in physiologically-sized constructs with tissue-like cell densities until recently. Sacrificial moulding is an alternative in which networks of rigid lattices of filaments are created to prevent subsequent matrix ingress. Our study describes a biocompatible sacrificial sugar-protein formulation; GSM, made from mixtures of inexpensive and readily available bio-grade materials. GSM can be cast/moulded or bioprinted as sacrificial filaments that can rapidly dissolve in an aqueous environment temperature-sensitively. GSM material can be used to engineer viable and vascularized human-scale tissues for regenerative medicine applications. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd.