Owing to their tissue-like elasticity, poly(ethylene glycol) (PEG)-based hydrogels are highly desirable as three-dimensional scaffolds for tissue regeneration. Also, their high permeability can mimic the native extracellular matrix. However, their applications are limited by their poor mechanical properties and bioinert nature, which restrict cell adhesion and spreading. This study aims to address both limitations by developing a novel hierarchical nanocomposite hydrogel (NC gel) composed of polyethylene glycol diacrylate (PEGDA) and hydroxyl mesoporous silica nanoparticles (MSNs-OH) via in situ free-radical polymerization. Structural and physicochemical characterization shows that MSNs-OH act as both reinforcing agents and adhesion sites in the hydrogel system, which significantly enhances mechanical properties and cellular affinity. Compared with the unmodified PEG hydrogels, which are fractured easily, MSNs-OH provide the PEG-based NC gels with flexibility due to interactions with PEGDA. Furthermore, the increased protein adsorption capability, the integration of hierarchical macro–mesoporous structure, as well as the introduction of silica, provide a favorable environment for the adhesion and spreading of rat marrow stem cells (RMSCs). These NC hydrogels show promise as scaffolds for tissue engineering.
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