Template-Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels.

Template-Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels.
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DOI:
10.1002/adhm.202102123
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发表时间:
2022-04
影响因子:
10
通讯作者:
Khademhosseini A
Khademhosseini A
中科院分区:
工程技术1区
文献类型:
--
作者:
Davoodi E;Montazerian H;Zhianmanesh M;Abbasgholizadeh R;Haghniaz R;Baidya A;Pourmohammadali H;Annabi N;Weiss PS;Toyserkani E;Khademhosseini A

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三维(3D)生物人工器官中相互连接的通路对于在厚的功能性3D组织中保持细胞活性是必不可少的。三维生物打印方法已经在功能图案化组织的生物制造中被广泛探索;然而,由于对低粘度生物墨水的控制不佳,这些方法是昂贵的并且局限于薄的组织层。在这里,可以通过水溶性明胶模板精确图案化的载有细胞的水凝胶通过经济的挤出3D打印塑料模板构建。基于三重周期最小表面(TPMS)设计的曲折的共连续塑料网络用作牺牲图案以形成二次牺牲明胶模板。这些模板最终用于形成细胞包封的明胶甲基丙烯酰(GelMA)水凝胶支架图案与复杂的互连途径。所提出的制造方法与可光交联的水凝胶相容,其中预聚物浇铸能够掺入具有高活力的高细胞群。载有细胞的水凝胶构建体的特征在于稳健的机械行为。体内研究表明,上级细胞向内生长到高渗透性构建体中。细胞包封的水凝胶内的可灌注的复杂互连网络可以帮助通过可渗透的内部通道工程化厚的和功能性的组织构建体,用于体内有效的细胞活性。开发了一种生物相容的、经济的和稳健的生物制造方法,以在由细胞外基质模拟软水凝胶(即,甲基丙烯酰明胶,GelMA)。具有互连孔的载有细胞的GelMA水凝胶在体外和体内表现出优异的机械可调性和支持细胞功能。
Interconnected pathways in three-dimensional (3D) bioartificial organs are essential to retaining cell activity in thick functional 3D tissues. Three-dimensional bioprinting methods have been widely explored in biofabrication of functionally patterned tissues; however, these methods are costly and confined to thin tissue layers due to poor control of low-viscosity bioinks. Here, cell-laden hydrogels that could be precisely patterned via water-soluble gelatin templates are constructed by economical extrusion 3D printed plastic templates. Tortuous co-continuous plastic networks, designed based on triply periodic minimal surfaces (TPMS), served as a sacrificial pattern to shape the secondary sacrificial gelatin templates. These templates were eventually used to form cell-encapsulated gelatin methacryloyl (GelMA) hydrogel scaffolds patterned with the complex interconnected pathways. The proposed fabrication process was compatible with photo-crosslinkable hydrogels wherein prepolymer casting enabled incorporation of high cell populations with high viability. The cell-laden hydrogel constructs were characterized by robust mechanical behavior. In vivo studies demonstrated a superior cell ingrowth into the highly permeable constructs. Perfusable complex interconnected networks within cell-encapsulated hydrogels may assist in engineering thick and functional tissue constructs through the permeable internal channels for efficient cellular activities in vivo. A biocompatible, economic, and robust biofabrication process was developed to form complex shapes and internal perfusable channels in multilayered thick tissue constructs made from extracellular matrix mimicking soft hydrogels (i.e., gelatin methacryloyl, GelMA). Cell-laden GelMA hydrogels with interconnected pores demonstrated excellent mechanical tunability and supported cell function in vitro and in vivo.
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