Binary Thiol-Acrylate Photopolymerization for the Design of Degradable Acetal-Functionalized Hydrogels

Degradable poly(ethylene glycol) (PEG) hydrogels provide a versatile platform for drug delivery and tissue engineering, and acetal functionalization now enables photo-processible PEG oligomers with selective and facile degradation in acidic environments. Tailored morphologies within acetal-functionalized hydrogels provided fundamental understanding of the multiphase network degradation. End group modification of poly(ethylene glycol) (Mn = 2,000 g/mol) with 2-(vinyloxy)ethyl acrylate yielded polyether precursors with both pH-sensitive acetals and photo-curable acrylate end groups. UV-initiated binary thiol-acrylate crosslinking of the acetal-functionalized PEG diacrylate with varied amounts of a thiol-functionalized three-armed PEG provided pH-degradable networks. Controlled stoichiometric imbalance of thiol and acrylate functionalities ensured predictable plateau storage moduli from 2 × 105 to 8 × 105 Pa. Small-angle X-ray scattering (SAXS) and dynamic mechanical analysis (DMA) confirmed that the thiol/acrylate molar ratio provided hydrogels with varying network architectures and crosslink densities. Spectroscopic monitoring of an imbedded mobile dye (Direct Red-81) quantified hydrogel degradation rates. Degradable hydrogels exhibited bulk degradation in acidic solution. Gels with the lowest crosslink density fully degraded in aqueous solutions at pH 3.4 within 60 h, while the highly crosslinked gels fully degraded over 3 weeks. All hydrogels displayed long-term stability in phosphate-buffered saline (pH 7.4) beyond 3 mo, suggesting stable hydrogels for selective degradation and cargo release in low pH environments.