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在合成水凝胶中实现可灌注微通道的简易光图案化以重现微生理环境。

Facile Photopatterning of Perfusable Microchannels in Synthetic Hydrogels to Recreate Microphysiological Environments.

机构信息

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332-0363, USA.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332-0535, USA.

出版信息

Adv Mater. 2023 Dec;35(52):e2306765. doi: 10.1002/adma.202306765. Epub 2023 Nov 22.

Abstract

The fabrication of perfusable hydrogels is crucial for recreating in vitro microphysiological environments. Existing strategies to fabricate complex microchannels in hydrogels involve sophisticated equipment/techniques. A cost-effective, facile, versatile, and ultra-fast methodology is reported to fabricate perfusable microchannels of complex shapes in photopolymerizable hydrogels without the need of specialized equipment or sophisticated protocols. The methodology utilizes one-step ultraviolet (UV) light-triggered cross-linking and a photomask printed on inexpensive transparent films to photopattern PEG-norbornene hydrogels. Complex and intricate patterns with high resolution, including perfusable microchannels, can be fabricated in <1 s. The perfusable hydrogel is integrated into a custom-made microfluidic device that permits connection to external pump systems, allowing continuous fluid perfusion into the microchannels. Under dynamic culture, human endothelial cells form a functional and confluent endothelial monolayer that remains viable for at least 7 days and respond to inflammatory stimuli. Finally, approach to photopattern norbornene hyaluronic acid hydrogels is adapted, highlighting the versatility of the technique. This study presents an innovative strategy to simplify and reduce the cost of biofabrication techniques for developing functional in vitro models using perfusable three-dimensional (3D) hydrogels. The approach offers a novel solution to overcome the complexities associated with existing methods, allowing engineering advanced in vitro microphysiological environments.

摘要

可灌注水凝胶的制备对于体外重建微观生理环境至关重要。现有的在水凝胶中制备复杂微通道的策略涉及复杂的设备/技术。本文报道了一种经济高效、简便、通用且超快的方法,可在无需专用设备或复杂方案的情况下,在光聚合水凝胶中制备具有复杂形状的可灌注微通道。该方法利用一步紫外(UV)光引发交联和打印在廉价透明薄膜上的光掩模来光图案化 PEG-降冰片烯水凝胶。可灌注水凝胶集成到定制的微流控装置中,可与外部泵系统连接,允许微通道内连续灌注流体。在动态培养下,人内皮细胞形成功能完整且连续的内皮单层,至少能存活 7 天,并对炎症刺激做出反应。最后,还采用了光图案化降冰片烯透明质酸水凝胶的方法,突出了该技术的通用性。本研究提出了一种创新策略,用于简化和降低使用可灌注三维(3D)水凝胶开发功能体外模型的生物制造技术的成本。该方法为克服现有方法相关的复杂性提供了新的解决方案,允许构建先进的体外微生理环境。

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