Hydrogel-Assisted Double Molding Enables Rapid Replication of Stereolithographic 3D Prints for Engineered Tissue Design.

Hydrogel-Assisted Double Molding Enables Rapid Replication of Stereolithographic 3D Prints for Engineered Tissue Design.
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DOI:
10.1021/acsami.3c02279
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发表时间:
2023-05-31
影响因子:
9.5
通讯作者:
Huebsch, Nathaniel
Huebsch, Nathaniel
中科院分区:
材料科学2区
文献类型:
--
作者:
Simmons, Daniel W.;Schuftan, David R.;Ramahdita, Ghiska;Huebsch, Nathaniel

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组织工程体外模型是生物医学研究中的重要工具。组织几何形状是功能的关键决定因素,但控制微尺度组织的几何形状仍然具有挑战性。增材制造方法已经成为一种有前途的手段,用于快速和迭代改变微器件的几何形状。然而,它已被证明,聚(二甲基硅氧烷)(PDMS)的交联往往被抑制在与立体光刻印刷材料的界面。虽然已经描述了复制模具立体光刻三维(3D)印刷品的方法,但是这些方法是不一致的,并且当不成功时经常导致印刷品破坏。此外,3D打印材料通常会将有毒化学物质溶于直接模制的PDMS中。在这里,我们开发了一种双重成型方法,可以将高分辨率立体光刻印刷品精确复制到聚二甲基硅氧烷(PDMS)弹性体中,从而促进快速设计迭代和高度并行化的样品生产。受失蜡铸造的启发,我们使用水凝胶作为中间模具,将高分辨率3D打印的高分辨率特征转移到PDMS中,而之前发表的工作集中在通过使用涂层和3D打印本身的后交联处理将PDMS直接成型到3D打印上。水凝胶的机械性能,包括交联密度,预测复制保真度。我们证明了这种方法复制各种形状的能力,这些形状是不可能使用传统上用于创建工程组织设计的光刻技术创建的。这种方法还能够将3D打印的特征复制到PDMS中,这在直接模塑中是不可能的,因为这些材料的刚度在脱模时导致材料断裂,而水凝胶中增加的韧性可以在复杂特征周围弹性变形并保持复制保真度。最后,我们强调了这种方法能够最大限度地减少有毒材料从原始3D打印转移到PDMS复制品中的可能性,从而增强其在生物应用中的用途。这种有毒物质转移的最小化在其他先前报道的描述将3D打印复制到PDMS中的方法中没有报道,我们通过创建干细胞衍生的微心肌来证明其用途。这种方法也可以用于未来的研究,以了解几何形状对工程组织及其组成细胞的影响。
Tissue-engineered in vitro models are an essential tool in biomedical research. Tissue geometry is a key determinant of function, but controlling the geometry of microscale tissues remains challenging. Additive manufacturing approaches have emerged as a promising means for rapid and iterative changes in the geometry of microdevices. However, it has been shown that poly(dimethylsiloxane) (PDMS) cross-linking is often inhibited at the interface of materials printed with stereolithography. While approaches to replica mold stereolithographic three-dimensional (3D) prints have been described, these methods are inconsistent and often lead to print destruction when unsuccessful. Additionally, 3D-printed materials often leach toxic chemicals into directly molded PDMS. Here, we developed a double molding approach that allows precise replication of high-resolution stereolithographic prints into poly(dimethylsiloxane) (PDMS) elastomer, facilitating rapid design iterations and highly parallelized sample production. Inspired by lost wax casting, we used hydrogels as intermediary molds to transfer high-resolution features from high-resolution 3D prints into PDMS, while previously published work focused on enabling direct molding of PDMS onto 3D prints through the use of coatings and post-cross-linking treatments of the 3D print itself. Hydrogel mechanical properties, including cross-link density, predict replication fidelity. We demonstrate the ability of this approach to replicate a variety of shapes that would be impossible to create using photolithography techniques traditionally used to create engineered tissue designs. This method also enabled the replication of 3D-printed features into PDMS that would not be possible with direct molding as the stiffness of these materials leads to material fracture when unmolding, while the increased toughness in the hydrogels can elastically deform around complex features and maintain replication fidelity. Finally, we highlight the ability of this method to minimize the potential for toxic materials to transfer from the original 3D print into the PDMS replica, enhancing its use for biological applications. This minimization of the transfer of toxic materials has not been reported in other previously reported methods describing replication of 3D prints into PDMS, and we demonstrate its use through the creation of stem cell-derived microheart muscles. This method can also be used in future studies to understand the effects of geometry on engineered tissues and their constitutive cells.
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