Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering

Alisa H. Isaac, Sarea Y. Recalde Phillips, Elizabeth Ruben, Matthew Estes, Varsha Rajavel, Talia Baig, Carol Paleti, Kirsten Landsgaard, Ryang Hwa Lee, Teja Guda, Michael F. Criscitiello, Carl Gregory and Daniel L. Alge ()
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Alisa H. Isaac: Texas A&M University
Sarea Y. Recalde Phillips: Texas A&M University
Elizabeth Ruben: Texas A&M University
Matthew Estes: Texas A&M University
Varsha Rajavel: Texas A&M University
Talia Baig: Texas A&M University
Carol Paleti: Texas A&M University
Kirsten Landsgaard: Texas A&M University
Ryang Hwa Lee: Texas A&M University
Teja Guda: The University of Texas at San Antonio
Michael F. Criscitiello: Texas A&M University
Carl Gregory: Texas A&M University
Daniel L. Alge: Texas A&M University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.

Date: 2024
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DOI: 10.1038/s41467-024-46327-3

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