The development of hydrophobic poly(ethylene glycol) (PEG) hydrogels, which are typically hydrophilic, could significantly enhance their application as artificial extracellular matrices. In this study, we designed PEG hydrogels with enhanced hydrophobicity through gel–gel phase separation (GGPS), a phenomenon that uniquely enhances hydrophobicity under ambient conditions, and we elucidated the pivotal role of elasticity in this process. We hypothesized that increased elasticity would amplify GGPS, thereby improving the hydrophobicity and cell adhesion on PEG hydrogel surfaces, despite their inherent hydrophilicity. To test this hypothesis, we engineered dilute oligo-PEG gels via a two-step process, creating polymer networks from tetra-PEG clusters with multiple reaction points. These oligo-PEG gels exhibited significantly higher elasticity, turbidity, and shrinkage upon water immersion compared to dilute PEG gels. Detailed characterization through confocal laser scanning microscopy, rheological measurements, and cell adhesion assays revealed distinct biphasic structures, increased hydrophobicity, and enhanced cell attachability in the dilute oligo-PEG gels. Our findings confirm that elasticity is crucial for effective GGPS, providing a novel method for tailoring hydrogel properties without chemical modification. This research introduces a new paradigm for designing biomaterials with improved cell-scaffolding capabilities, offering significant potential for tissue engineering and regenerative medicine.

中文翻译：

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具有增强疏水性的簇状聚乙二醇水凝胶中的凝胶-凝胶相分离


疏水性聚乙二醇 （PEG） 水凝胶（通常具有亲水性）的开发可以显着增强其作为人工细胞外基质的应用。在这项研究中，我们通过凝胶-凝胶相分离 （GGPS） 设计了具有增强疏水性的 PEG 水凝胶，这种现象在环境条件下独特地增强了疏水性，我们阐明了弹性在此过程中的关键作用。我们假设增加的弹性会放大 GGPS，从而改善 PEG 水凝胶表面的疏水性和细胞粘附性，尽管它们具有固有的亲水性。为了验证这一假设，我们通过两步工艺设计了稀释的 oligo-PEG 凝胶，从具有多个反应点的 tetra-PEG 簇中创建聚合物网络。与稀释的 PEG 凝胶相比，这些 oligo-PEG 凝胶在水浸入时表现出明显更高的弹性、浊度和收缩率。通过共聚焦激光扫描显微镜、流变学测量和细胞粘附测定进行详细表征，揭示了稀释的 oligo-PEG 凝胶中独特的双相结构、增加的疏水性和增强的细胞附着性。我们的研究结果证实，弹性对于有效的 GGPS 至关重要，提供了一种无需化学改性即可定制水凝胶特性的新方法。这项研究为设计具有改进的细胞支架能力的生物材料引入了一种新的范式，为组织工程和再生医学提供了巨大的潜力。