PROJECT SUMMARY
Poly(ethylene glycol) (PEG) based hydrogels are widely used in medical devices and are being studied for the
delivery of protein and cellular therapeutics. While these biomaterials are widely regarded as biologically inert,
concerns over PEG’s immunogenicity have emerged in recent years. It has been estimated that 20-30% of the
population has antibodies against PEG due to exposure via pharmaceuticals, cosmetics, and other PEG-
containing products. While an anti-PEG immune response has been found to reduce the efficacy of
intravenously administered PEGylated drugs, the impact on the biocompatibility of PEG hydrogels has not
previously been studied and is currently unknown. To address this knowledge gap, this project has two
Specific Aims that encompass comprehensive in vivo testing to evaluate the host response to PEG hydrogels
of varying physical and chemical properties. In these experiments, PEG hydrogels will be implanted
subcutaneously in mice, and the host response will be evaluated at early, intermediate, and late timepoints
using histology, immunohistochemistry, flow cytometry, and blood testing. The key comparison in these
experiments will be between animals conditioned to mount an anti-PEG response and immunologically naïve
controls. The project has two Specific Aims. Aim 1 focuses on PEG hydrogel formulations that lack
hydrolytically and enzymatically cleavable linkers. Hydrogels that differ in modulus, crosslinking chemistry, and
functionalization with cell-adhesive peptides will be systematically studied. Aim 2 focuses on PEG hydrogel
formulations that contain hydrolytically and enzymatically degradable linkers. In addition to evaluating the host
response, the impact of the anti-PEG immune response on the in vivo degradation rate of these hydrogels will
be investigated via non-invasive imaging in a longitudinal study. The results of this project will either alleviate
concerns over PEG immunogenicity for biomaterial implants or motivate future investigations on strategies to
mitigate its effects.