Finding the sweet spot: a library of hydrogels with tunable degradation for tissue model development
Finding the sweet spot: a library of hydrogels with tunable degradation for tissue model development
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DOI：
10.1039/d1tb02436a
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发表时间：
2022-03-07
影响因子：
7
通讯作者：
Lavik, Erin
中科院分区：
文献类型：
--
作者：
Pandala, Narendra;LaScola, Michael A.;Lavik, Erin
体外模型对于理解细胞机制和药物筛选等应用是有价值的工具。水凝胶生物材料通过模拟细胞外基质和体内微环境来促进体外模型。然而，细胞在不降解的水凝胶中形成组织可能是具有挑战性的。相反，如果水凝胶降解太多或太快，则组织模型可能难以以高通量方式评估。在本文中，我们提出了一种聚（烯丙胺）（PAA）为基础的合成水凝胶系统，它可以调整控制的水凝胶支架提供的机械和化学线索。PAA是一种具有多种生物医学应用的聚阳离子，包括小分子、核酸和蛋白质的递送。基于PAA和聚乙二醇（PEG），我们开发了一种合成的非降解系统，具有潜在的长期培养应用。然后，我们创建了第二组凝胶，其将PAA与聚-l-赖氨酸（PLL）组合以产生具有独特降解动力学的半降解凝胶库。在这项工作中，我们提出了水凝胶系统的合成，表征和降解曲线沿着与细胞数据表明，一个子集的凝胶支持内皮细胞索状结构的形成。
In vitro models are valuable tools for applications including understanding cellular mechanisms and drug screening. Hydrogel biomaterials facilitate in vitro models by mimicking the extracellular matrix and in vivo microenvironment. However, it can be challenging for cells to form tissues in hydrogels that do not degrade. In contrast, if hydrogels degrade too much or too quickly, tissue models may be difficult to assess in a high throughput manner. In this paper, we present a poly(allylamine) (PAA) based synthetic hydrogel system which can be tuned to control the mechanical and chemical cues provided by the hydrogel scaffold. PAA is a polycation with several biomedical applications, including the delivery of small molecules, nucleic acids, and proteins. Based on PAA and poly(ethylene glycol) (PEG), we developed a synthetic non-degradable system with potential applications for long-term cultures. We then created a second set of gels that combined PAA with poly-l-lysine (PLL) to generate a library of semi-degradable gels with unique degradation kinetics. In this work, we present the hydrogel systems' synthesis, characterization, and degradation profiles along with cellular data demonstrating that a subset of gels supports the formation of endothelial cell cord-like structures.