The dynamic interplay between cells and their native extracellular matrix (ECM) influences cellular behavior, imposing a challenge in biomaterial design. Dynamic covalent hydrogels are viscoelastic and show self-healing ability, making them a potential scaffold for recapitulating native ECM properties. We aimed to implement kinetically and thermodynamically distinct crosslinkers to prepare self-healing dynamic hydrogels to explore the arising properties and their effects on cellular behavior. To do so, aldehyde-substituted hyaluronic acid (HA) was synthesized to generate imine, hydrazone, and oxime crosslinked dynamic covalent hydrogels. Differences in equilibrium constants of these bonds yielded distinct properties including stiffness, stress relaxation, and self-healing ability. The effects of degree of substitution (DS), polymer concentration, crosslinker to aldehyde ratio, and crosslinker functionality on hydrogel properties were evaluated. The self-healing ability of hydrogels was investigated on samples of the same and different crosslinkers and DS to obtain hydrogels with gradient properties. Subsequently, human dermal fibroblasts were cultured in 2D and 3D to assess the cellular response considering the dynamic properties of the hydrogels. Moreover, assessing cell spreading and morphology on hydrogels having similar modulus but different stress relaxation rates showed the effects of matrix viscoelasticity with higher cell spreading in slower relaxing hydrogels.

中文翻译：

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希夫碱交联透明质酸水凝胶具有可调节和细胞指导性时间依赖性机械性能


细胞与其天然细胞外基质 (ECM) 之间的动态相互作用影响细胞行为，给生物材料设计带来挑战。动态共价水凝胶具有粘弹性并显示出自愈能力，使其成为重现天然 ECM 特性的潜在支架。我们的目标是使用动力学和热力学上不同的交联剂来制备自修复动态水凝胶，以探索所产生的特性及其对细胞行为的影响。为此，合成了醛取代的透明质酸（HA）以生成亚胺、腙和肟交联的动态共价水凝胶。这些键平衡常数的差异产生了不同的特性，包括刚度、应力松弛和自愈能力。评估了取代度（DS）、聚合物浓度、交联剂与醛的比例以及交联剂官能度对水凝胶性能的影响。对相同和不同交联剂和 DS 的样品研究水凝胶的自修复能力，以获得具有梯度性能的水凝胶。随后，在 2D 和 3D 中培养人真皮成纤维细胞，以评估考虑水凝胶动态特性的细胞反应。此外，评估具有相似模量但不同应力松弛率的水凝胶上的细胞铺展和形态显示了基质粘弹性的影响，并且在较慢的松弛水凝胶中具有较高的细胞铺展。