Reed Jeffrey A, Retterer Scott T, Hansen Ryan R
Tim Taylor Department of Chemical Engineering, Kansas State University, Manhattan, Kansas 66506, United States.
Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, United States.
ACS Appl Mater Interfaces. 2025 Sep 17;17(37):51919-51930. doi: 10.1021/acsami.5c14670. Epub 2025 Sep 2.
Stimuli-responsive hydrogels that provide controlled degradation can be used as bacteria delivery systems for advanced therapeutic applications. Here, we report the first use of photodegradable hydrogels as materials that can direct bacterial movement, tune mean bacteria speed, and control bacteria delivery through spatiotemporal control of degradation. Hydrogels were formed using base-catalyzed Michael addition reactions between photodegradable poly(ethylene glycol) (PEG) -nitrobenzyl diacrylate macromers and PEG tetra-thiol cross-linkers within microfluidic channels. Nutrient gradients were generated across the channel, and micron-scale regions of the hydrogel were partially degraded by exposure to controlled doses (2.1-168 mJ/mm) of patterned 365 nm light. Hydrogel degradation was then characterized using fluorescence visualization of fluorescein-labeled hydrogels. Following characterization, expressing green fluorescent protein was introduced into the device, and its movement up the nutrient gradient was monitored using time-lapse fluorescence microscopy to enable a systematic study of bacteria chemotaxis through the hydrogels at varied levels of degradation. showed minimal adhesion to partially degraded PEG hydrogels, and bacteria mean speed and mean directional change were tunable according to the level of hydrogel photodegradation, with a 2.6-fold difference in mean cell speed measured across the partially degraded hydrogel regions. Finally, the ability to alter bacteria speed and directionality through tunable degradation and without significant adhesion was used to achieve controlled release profiles of bacteria to delivery sites. These findings advance the use of PEG-based hydrogel materials as delivery vehicles for bacterial therapeutic applications and other living material applications that require controlled bacteria transport.
具有可控降解性的刺激响应水凝胶可作为细菌递送系统用于先进的治疗应用。在此，我们报道了首次将光降解水凝胶用作能够引导细菌运动、调节细菌平均速度并通过时空控制降解来控制细菌递送的材料。水凝胶是在微流控通道内通过光降解性聚乙二醇（PEG）-硝基苄基二丙烯酸酯大分子单体与PEG四硫醇交联剂之间的碱催化迈克尔加成反应形成的。在通道内产生营养梯度，通过暴露于可控剂量（2.1 - 168 mJ/mm）的图案化365 nm光，使水凝胶的微米级区域部分降解。然后使用荧光素标记水凝胶的荧光可视化来表征水凝胶的降解。表征之后，将表达绿色荧光蛋白的细菌引入装置，并使用延时荧光显微镜监测其沿营养梯度向上的运动，以便在不同降解水平下通过水凝胶对细菌趋化性进行系统研究。结果表明细菌对部分降解的PEG水凝胶的粘附极小，并且细菌平均速度和平均方向变化可根据水凝胶光降解水平进行调节，在部分降解的水凝胶区域测得的平均细胞速度相差2.6倍。最后，通过可调降解且无明显粘附来改变细菌速度和方向性的能力被用于实现细菌向递送部位的控释曲线。这些发现推动了基于PEG的水凝胶材料作为细菌治疗应用和其他需要可控细菌运输的生物材料应用的递送载体的使用。
