title: Linking the foreign body response and protein adsorption to PEG-based hydrogels using proteomics.
abstract: Poly(ethylene glycol) (PEG) hydrogels with their highly tunable properties are promising implantable materials, but as with all non-biological materials, they elicit a foreign body response (FBR). Recent studies, however, have shown that incorporating the oligopeptide RGD into PEG hydrogels reduces the FBR. To better understand the mechanisms involved and the role of RGD in mediating the FBR, PEG, PEG-RGD and PEG-RDG hydrogels were investigated. After a 28-day subcutaneous implantation in mice, a thinner and less dense fibrous capsule formed around PEG-RGD hydrogels, while PEG and PEG-RDG hydrogels exhibited stronger, but similar FBRs. Protein adsorption to the hydrogels, which is considered the first step in the FBR, was also characterized. In vitro experiments confirmed that serum proteins adsorbed to PEG-based hydrogels and were necessary to promote macrophage adhesion to PEG and PEG-RDG, but not PEG-RGD hydrogels. Proteins adsorbed to the hydrogels in vivo were identified using liquid chromatography-tandem mass spectrometry. The majority (245) of the total proteins (≥300) that were identified was present on all hydrogels with many proteins being associated with wounding and acute inflammation. These findings suggest that the FBR to PEG hydrogels may be mediated by the presence of inflammatory-related proteins adsorbed to the surface, but that macrophages appear to sense the underlying chemistry, which for RGD improves the FBR.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA; Biofrontiers Institute, University of Colorado, Boulder, CO 80309, USA. Electronic address: Mark.Swartzlander@colorado.edu.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Swartzlander
authors.affiliation: Institute of Biochemistry, ETH Zürich, Switzerland. Electronic address: barnes@biol.bc.ethz.ch.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Barnes
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA. Electronic address: Blakney@uw.edu.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Blakney
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA. Electronic address: Joel.Kaar@colorado.edu.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Kaar
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: Themis.Kyriakides@yale.edu.
authors.forename: Themis R
authors.initials: TR
authors.lastname: Kyriakides
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA; Biofrontiers Institute, University of Colorado, Boulder, CO 80309, USA; Material Science and Engineering Program, University of Colorado, Boulder, CO 80309, USA. Electronic address: Stephanie.Bryant@colorado.edu.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bryant
mesh_terms: D000327:Adsorption; D000818:Animals; D002448:Cell Adhesion; D005549:Foreign-Body Reaction / Q000139:chemically induced*; D063990:Gene Ontology; D020100:Hydrogels / Q000009:adverse effects*; D008264:Macrophages; D008297:Male; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D013057:Spectrum Analysis
chemical_list: D020100:Hydrogels; D009842:Oligopeptides; D011506:Proteins; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid
keywords: Foreign body response; Hydrogel; Macrophage; Mass spectrometry; Poly(ethylene glycol); Protein adsorption