Department of Biomedical Engineering, University of Texas, Austin, TX, 78712, USA.
Department of Biomedical Engineering, University of Texas, Austin, TX, 78712, USA; McKetta Department of Chemical Engineering, University of Texas, Austin, TX, 78712, USA; Division of Molecular Therapeutics and Drug Delivery, College of Pharmacy, University of Texas, Austin, TX, 78712, USA; Departments of Surgery and Pediatrics, Dell Medical School, University of Texas, Austin, TX, 78712, USA.
Biomaterials. 2023 Oct;301:122272. doi: 10.1016/j.biomaterials.2023.122272. Epub 2023 Aug 9.
Synthetic hydrogels are widely used as artificial 3D environments for cell culture, facilitating the controlled study of cell-environment interactions. However, most hydrogels are limited in their ability to represent the physical properties of biological tissues because stiffness and solute transport properties in hydrogels are closely correlated. Resultingly, experimental investigations of cell-environment interactions in hydrogels are confounded by simultaneous changes in multiple physical properties. Here, we overcame this limitation by simultaneously manipulating four structural parameters to synthesize a library of multi-arm poly (ethylene glycol) (PEG) hydrogel formulations with robustly decoupled stiffness and solute transport. This structural design approach avoids chemical alterations or additions to the network that might have unanticipated effects on encapsulated cells. An algorithm created to statistically evaluate stiffness-transport decoupling within the dataset identified 46 of the 73 synthesized formulations as robustly decoupled. We show that the swollen polymer network model accurately predicts 11 out of 12 structure-property relationships, suggesting that this approach to decoupling stiffness and solute transport in hydrogels is fundamentally validated and potentially broadly applicable. Furthermore, the unprecedented control of hydrogel network structure provided by multi-arm PEG hydrogels confirmed several fundamental modeling assumptions. This study enables nuanced hydrogel design for uncompromised investigation of cell-environment interactions.
合成水凝胶被广泛用作细胞培养的人工 3D 环境，有助于对细胞-环境相互作用进行受控研究。然而，由于水凝胶的硬度和溶质传输性质密切相关，大多数水凝胶在代表生物组织的物理性质方面能力有限。因此，水凝胶中细胞-环境相互作用的实验研究受到多种物理性质同时变化的干扰。在这里，我们通过同时操纵四个结构参数来克服这一限制，从而合成了一系列具有稳健解耦硬度和溶质传输性能的多臂聚乙二醇（PEG）水凝胶配方库。这种结构设计方法避免了对网络进行化学改变或添加，因为这可能会对包封的细胞产生意想不到的影响。为了在数据集中统计评估刚度-传输解耦，我们创建了一个算法，该算法确定了 73 种合成配方中的 46 种具有稳健的解耦。我们表明，溶胀聚合物网络模型准确预测了 12 个结构-性能关系中的 11 个，这表明这种解耦水凝胶硬度和溶质传输的方法在根本上是有效的，并且具有潜在的广泛适用性。此外，多臂 PEG 水凝胶对水凝胶网络结构的前所未有的控制证实了几个基本的建模假设。这项研究实现了水凝胶的精细设计，可用于对细胞-环境相互作用进行毫不妥协的研究。
