Linking the foreign body response and protein adsorption to PEG-based hydrogels using proteomics |
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| Affiliation: | 1. Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA;2. Biofrontiers Institute, University of Colorado, Boulder, CO 80309, USA;3. Institute of Biochemistry, ETH Zürich, Switzerland;4. Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA;5. Material Science and Engineering Program, University of Colorado, Boulder, CO 80309, USA;1. Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA;2. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan;1. Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan;2. Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan;3. Department of Prosthodontics, Kagoshima University Graduate School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan;4. Graduate School of Environmental Studies, Tohoku University, 6-6-20 Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan;5. Department of Chemistry, Faculty of Economics, Keio University, 4-4-1 Yokohama, Kanagawa 223-8521, Japan;1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. Department of Basic Medical Sciences, Hebei United University, Tangshan 063000, China;3. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Science, Beijing 100850, China;4. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;1. Department of Genetics, Yale University, New Haven, CT 06520, USA;2. Department of Pathology, Yale University, New Haven, CT 06520, USA;3. Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA;4. Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, New Haven, CT 06520, USA;1. Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK;2. School of Computer Science, Centre for Mesoscience and Nanotechnology, The University of Manchester, Manchester, UK |
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| 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. |
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| Keywords: | Poly(ethylene glycol) Macrophage Hydrogel Foreign body response Protein adsorption Mass spectrometry |
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