Mechanical Programming of PEGDA‐ β ‐CD Polyrotaxane‐Based Hydrogels via Host–Guest Molecular Recognition

ABSTRACT Polyrotaxane‐based hydrogels with mechanically interlocked structures offer unique opportunities for designing biomaterials with tunable mechanical properties in tissue engineering. However, the polyrotaxane structure based on poly(ethylene glycol) (PEG) and β ‐cyclodextrin ( β ‐CD) is considered negligible in the aqueous phase, limiting its integration into well‐defined hydrogel networks. Here, we report a series of hydrogels constructed from poly(ethylene glycol) diacrylate (PEGDA)‐ β ‐CD polyrotaxanes and gelatin (Gel), loaded with curcumin as a therapeutic model. We demonstrate that the increasing number of threaded β ‐CD units on PEGDA chains induced an evolution of gel microstructure from disordered porous to ordered laminar morphology, thereby transforming the mechanical behavior from highly elastic, low‐dissipated (13.53%) to high‐damping states (46.56%), accompanied by enhanced toughness and modulus. Notably, low threading density variants exhibited desirable elasticity and recovery suitable for skin wound dressings, while higher threading densities enabled mimicking of highly dissipative biological tissues. In vivo studies further demonstrated the excellent wound healing performance of these hydrogels, due to their suitable mechanical properties and anti‐inflammatory properties. In summary, this study highlights the critical role of polyrotaxane threading density in coupling supramolecular structure with mechanical and biological functions, providing a versatile strategy for advanced tissue engineering materials.