Department of Mechanical Engineering , Tsinghua University , Beijing 100084 , China.
Department of Bioengineering , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
ACS Appl Mater Interfaces. 2018 Apr 18;10(15):12424-12430. doi: 10.1021/acsami.7b19537. Epub 2018 Apr 9.
Multilayer (ML) hydrogels are useful to achieve stepwise and heterogeneous control over the organization of biomedical materials and cells. There are numerous challenges in the development of fabrication approaches toward this, including the need for mild processing conditions that maintain the integrity of embedded compounds and the versatility in processing to introduce desired complexity. Here, we report a method to fabricate heterogeneous multilayered hydrogels based on diffusion-induced gelation. This technique uses the quick diffusion of ions and small molecules (i.e., photoinitiators) through gel-sol or gel-gel interfaces to produce hydrogel layers. Specifically, ionically (e.g., alginate-based) and covalently [e.g., gelatin methacryloyl (GelMA-based)] photocross-linked hydrogels are generated in converse directions from the same interface. The ML (e.g., seven layers) ionic hydrogels can be formed within seconds to minutes with thicknesses ranging from tens to hundreds of micrometers. The thicknesses of the covalent hydrogels are determined by the reaction time (or the molecule diffusion time). Multiwalled tubular structures (e.g., mimicking branched multiwalled vessels) are mainly investigated in this study based on a removable gel core, but this method can be generalized to other material patterns. The process is also demonstrated to support the encapsulation of viable cells and is compatible with a range of thermally reversible core materials (e.g., gelatin and Pluronic F127) and covalently cross-linked formulations (e.g., GelMA and methacrylated hyaluronic acid). This biofabrication process enhances our ability to fabricate a range of structures that are useful for biomedical applications.
多层（ML）水凝胶可用于实现对生物医学材料和细胞的组织的逐步和不均匀控制。在开发制造方法方面存在许多挑战，包括需要温和的处理条件以保持嵌入化合物的完整性，以及具有引入所需复杂性的多功能加工能力。在这里，我们报告了一种基于扩散诱导凝胶化来制造不均匀多层水凝胶的方法。该技术利用离子和小分子（例如光引发剂）通过凝胶-溶胶或凝胶-凝胶界面的快速扩散来产生水凝胶层。具体而言，通过相同的界面从相反方向生成离子型（例如基于藻酸盐的）和共价型[例如明胶甲基丙烯酰基（基于 GelMA 的）]光交联水凝胶。可以在几秒钟到几分钟内形成具有数十到数百微米厚度的 ML（例如七层）离子水凝胶。共价水凝胶的厚度取决于反应时间（或分子扩散时间）。本研究主要基于可去除的凝胶芯研究了多壁管状结构（例如模拟分支多壁血管），但该方法可以推广到其他材料图案。该过程还被证明可以支持活细胞的封装，并且与各种热可逆核心材料（例如明胶和 Pluronic F127）和共价交联制剂（例如 GelMA 和甲基丙烯酰化透明质酸）兼容。这种生物制造过程提高了我们制造一系列对生物医学应用有用的结构的能力。
