Assessing the Impact of the Anti-PEG Response on Tissue Engineering Efficacy with PEG Hydrogels

Abstract

Poly(ethylene glycol) (PEG) is a blank-slate biomaterial that is commonly used in pharmaceuticals, drug delivery, and tissue regeneration applications. However, there are growing concerns about PEG immunogenicity, and it has been reported that as much as 72% of the healthy human population has developed antibodies against PEG. Anti-PEG antibody prevalence has been linked to the accelerated blood clearance of PEG-conjugated therapeutics and anaphylaxis-like reactions have been reported in patients who have been administered PEG or PEG-conjugated pharmaceuticals. Concerning the recent findings, there is a need to investigate how PEG-antibody interactions affect the efficacy of PEG-based tissue engineering therapies.

To investigate this, we first studied PEG MAP hydrogel annealing by Tz-click chemistry as well as the utility of PEG MAP hydrogels for growth factor and cell delivery. Next, we examined macrophage response to opsonized PEG hydrogels and host response to PEG hydrogels in PEG sensitized mice. Finally, we implanted BMP-2 loaded MAP hydrogels in calvarial defects of PEG sensitized mice and determined anti-PEG host response effects on bone regeneration.

PEG MAP gels showed high retention of growth factors and increased cell spreading and proliferation of encapsulated periodontal stem cells. When macrophages were exposed to opsonized PEG gels, inflammatory cytokine secretion, macrophage fusion, and migration in response to complement activation were increased. When PEG hydrogels were subcutaneously implanted in PEG sensitized mice, females exhibited isotype switching as IgM antibody concentration decreased and IgG antibody concentration increased. When BMP-2 loaded MAP hydrogels were implanted in calvarial defects of PEG sensitized mice, data revealed that sensitization of PEG led to a significant increase in bone volume in male mice at 6 weeks. Histology revealed disorganized bone structure and increased ectopic bone volume in mice with anti-PEG antibodies compared to PEG naive mice with the same treatment.

The data obtained suggests that PEG MAP gels are a promising platform for tissue regeneration, PEG sensitization has significant effects on immune cell response, and the presence of anti-PEG antibodies can change the outcomes of bone regeneration utilizing PEG-based hydrogels. These potential effects warrant further investigation in future studies.