Modular microporous hydrogels formed from microgel beads with orthogonal thermo-chemical responsivity: Microfluidic fabrication and characterization
Modular microporous hydrogels formed from microgel beads with orthogonal thermo-chemical responsivity: Microfluidic fabrication and characterization
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DOI：
10.1016/j.mex.2019.07.018
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发表时间：
2019-01-01
期刊：
影响因子：
1.9
通讯作者：
Khademhosseini, Ali
中科院分区：
文献类型：
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作者：
Sheikhi, Amir;de Rutte, Joseph;Khademhosseini, Ali
尽管在设计可注射本体水凝胶方面取得了显著进展，但无法控制孔互连性并将其与基质刚度解耦极大地限制了刚性可流动水凝胶用于3D细胞工程的适用性，例如，在硬组织工程中。为了克服这一持续的挑战，在这里，我们介绍了一种通用的方法，将具有化学交联部分的热敏性大分子转化为可退火的结构单元，以自下而上的方法形成3D微孔珠状支架。特别地，我们显示明胶甲基丙烯酰基（GelMA），一种在组织工程中广泛使用的生物材料，可以使用简单的微流体方法转化为物理交联的微珠，然后通过微珠悬浮液的流动和原位化学交联来制造具有互连孔的微孔珠状GelMA（B-GelMA）支架，促进细胞功能和快速生长。（在几分钟内）在刚性支架中进行3D接种，这在本体凝胶对应物中是不可能的。这种新的方法可能为下一代由广泛的天然和合成生物材料组成的具有正交孔隙率和刚度的模块化水凝胶奠定基础。这种方法将众所周知的流动聚焦微流体设备与简单的后处理步骤相结合，以制造微孔支架。温度-微珠的驱动物理交联使得能够在没有进一步化学反应的情况下容易地纯化凝胶结构单元。提供了一种制造微孔支架的简单方法，该方法克服了新出现的珠状支架的一些挑战，包括氧介导的受损交联。(C)2019作者由爱思唯尔公司出版
Despite the significant advances in designing injectable bulk hydrogels, the inability to control the pore interconnectivity and decoupling it from the matrix stiffness has tremendously limited the applicability of stiff, flowable hydrogels for 3D cellular engineering, e.g., in hard tissue engineering. To overcome this persistent challenge, here, we introduce a universal method to convert thermosensitive macromolecules with chemically-crosslinkable moieties into annealable building blocks, forming 3D microporous beaded scaffolds in a bottom-up approach. In particular, we show gelatin methacryloyl (GelMA), a widely used biomaterial in tissue engineering, maybe converted into physically-crosslinked microbeads using a facile microfluidic approach, followed by flow of the microbead suspension and chemical crosslinking in situ to fabricate microporous beaded GelMA (B-GelMA) scaffolds with interconnected pores, promoting cell functionality and rapid (within minutes) 3D seeding in stiff scaffolds, which are otherwise impossible in the bulk gel counterparts. This novel approach may set the stage for the next generation modular hydrogels with orthogonal porosity and stiffness made up of a broad range of natural and synthetic biomaterials.This method combines well-known flow focusing microfluidic devices with facile post-processing steps to fabricate microporous scaffolds.Temperature-driven physical crosslinking of the microbeads enables the facile purification of gel building blocks without further chemical reactions.This method provides a simple approach to fabricate microporous scaffolds, which overcomes some of the challenges of newly emerging beaded scaffolds, including oxygen-mediated impaired crosslinking. (C) 2019 The Authors. Published by Elsevier B.V.