Tailoring hydrogel mesh structure through custom-designed poly(ether urethane)s for advanced drug delivery systems in biomedical applications

Hydrogel mesh size plays a pivotal role in determining physico-chemical and mechanical properties, making these materials versatile for tissue engineering and drug delivery applications. Herein, we report the tunability of mesh size in Schiff-base hydrogels through tailored poly(ether urethane) (PEU) chemistry. Three aldehyde-terminated PEUs (PEU-CHO) with different molecular weights (M̄n = 1.6–9 kDa, D ≈ 1.4) were synthesized and employed as crosslinkers for a high-molecular-weight amine-functionalized PEU (PEU-NH2, M̄n = 25 kDa, D = 1.7). Hydrogels formed upon mixing PEU aqueous solutions and underwent gelation within a few hours. Rheology revealed highly strain-resistant gels (up to 1200%) with tunable mechanical properties and mesh sizes of 18–50 nm. Thermal analyses showed ≈60% of freezable water and similar distributions in pore size (2 nm–2 µm). Notably, mesh size strongly affected the fluid uptake, the swelling behavior monitored in real-time via Magnetic Resonance Imaging, and the diffusion of model molecules. Smaller-mesh hydrogels exhibited diffusion-driven release for fluorescein isothiocyanate-dextran (FD) with M̄w = 4 and 10 kDa, whereas anomalous diffusion occurred for FD 70 kDa, confirming network-hindered transport. This work provides a versatile strategy of molecular design to finely regulate hydrogel structure and performance, enabling the development of tailored biomaterials in the biomedical field.