A Diffusion‐Based Evaluation of Transport‐Effective Network Characteristics in Fully PEG ‐Based Tetra/Linear‐ PEG Hydrogels

ABSTRACT Tetra‐arm poly(ethylene glycol) (tetra‐PEG) hydrogels are well‐defined PEG‐based polymer networks with excellent optical transparency; however, their relatively restricted transport pathways can limit the diffusion of macromolecules. In this work, we present a diffusion‐based strategy to evaluate transport‐effective characteristics of PEG hydrogels using macromolecular diffusion measurements. Hydrogels were prepared using 20 kDa four‐arm PEG–succinimidyl ester crosslinked with either four‐arm PEG–amine (TP) or bifunctional linear PEG diamine (TP + LP), forming 4 × 4 and 2 × 4 PEG network architectures, respectively. Time‐resolved diffusion experiments were performed using 70 kDa fluorescein isothiocyanate (FITC)–dextran as a model macromolecule, and effective diffusion coefficients ( D eff ) were obtained from the release profiles. An obstruction‐based diffusion model was subsequently applied to estimate diffusion‐effective characteristic length scales associated with macromolecular transport. The TP + LP formulation exhibited enhanced FITC–dextran transport, with a mean effective diffusion coefficient approximately 3.4‐fold higher than that of TP. The corresponding model‐derived diffusion‐effective characteristic lengths were 8.7 ± 0.9 nm for TP and 24 ± 7 nm for TP + LP. These results demonstrate diffusion measurements can provide a comparative evaluation of transport accessibility in PEG hydrogel formulations. The present study provides a proof‐of‐concept approach for relating PEG network formulation to macromolecular transport behavior.