photocurable bioink

  • 文章类型: Journal Article
    人体肠道结构和功能在体外的准确复制对了解肠道的发育和疾病发生具有重要意义。然而,大多数体外研究通常局限于2D模型,2.5D器官芯片或3D类器官,不能完全概括组织结构,体内发现的微环境和细胞区室化。在这里,包含肠道特征的厘米级肠道组织,如中空管状结构,毛细血管和紧密相连的上皮,具有体内环状褶皱,地穴-绒毛,微绒毛是通过3D嵌入生物打印构建的。在我们的战略中,一种由甲基丙烯酸酯化明胶组成的新型光固化生物墨水,甲基丙烯酸酯化海藻酸钠和聚(乙二醇)二丙烯酸酯被开发用于制造肠道模型。通过模型的拓扑结构诱导植入腔内的Caco-2细胞产生微绒毛,地穴-绒毛,和紧密连接,模拟肠上皮屏障。模型内包裹的人脐静脉内皮细胞逐渐形成微血管,模仿肠道中密集的毛细血管网络。这个肠样组织,它非常类似于人类肠道的结构和细胞排列,可以作为预测新药对肠道的治疗和毒副作用的平台。
    Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.
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  • 文章类型: Journal Article
    3D生物打印具有快速和精确的水凝胶构建体工程的潜力,可以模拟健康角膜的结构和光学复杂性。然而,现有的光活化生物墨水在角膜打印中的使用受到细胞相容性差的限制,使用细胞毒性光引发剂(PI),低光交联效率,和印刷材料的不透明/有色表面。在这里,我们报告了一种快速治愈的,非细胞毒性,使用新型水溶性苯甲酰基次膦酸盐PI和可光交联的甲基丙烯酸酯化透明质酸(HAMA)的光学透明生物打印系统。与市售PI相比,新开发的PI,苯甲酰基(苯基)次膦酸锂(BP),显示在可见光下增加的光引发效率和低细胞毒性。使用催化量的BP,基于HA的生物墨水在低能量可见光照射(405nm,<1Jcm-2)。通过混合低(10kDa)和高(100kDa)分子量(MW)的HAMA,形成多长度网络,进一步提高了可光固化生物墨水的机械性能和可印刷性。作为角膜支架的潜在应用,使用MW混合的HAMA/BP生物墨水和数字光处理打印机制造基质细胞的圆顶形结构。基于HA的可光固化生物墨水表现出良好的细胞相容性(80%-95%),快速固化动力学(<5s),和优异的光学透明度(在可见光范围内>90%),可能使它们适用于角膜组织工程。
    3D bioprinting has the potential for the rapid and precise engineering of hydrogel constructs that can mimic the structural and optical complexity of a healthy cornea. However, the use of existing light-activated bioinks for corneal printing is limited by their poor cytocompatibility, use of cytotoxic photoinitiators (PIs), low photo-crosslinking efficiency, and opaque/colored surface of the printed material. Herein, we report a fast-curable, non-cytotoxic, optically transparent bioprinting system using a new water-soluble benzoyl phosphinate-based PI and photocrosslinkable methacrylated hyaluronic acid (HAMA). Compared with commercially available PIs, the newly developed PI, lithium benzoyl (phenyl) phosphinate (BP), demonstrated increased photoinitiation efficiency under visible light and low cytotoxicity. Using a catalytic amount of BP, the HA-based bioinks quickly formed 3D hydrogel constructs under low-energy visible-light irradiation (405 nm, <1 J cm-2). The mechanical properties and printability of photocurable bioinks were further improved by blending low (10 kDa) and high (100 kDa) molecular weight (MW) HAMA by forming multilength networks. For potential applications as corneal scaffolds, stromal cell-laden dome-shaped constructs were fabricated using MW-blended HAMA/BP bioink and a digital light processing printer. The HA-based photocurable bioinks exhibited good cytocompatibility (80%-95%), fast curing kinetics (<5 s), and excellent optical transparency (>90% in the visible range), potentially making them suitable for corneal tissue engineering.
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