Linking the foreign body response and protein adsorption to PEG-based hydrogels using proteomics

Area of Science:

• Biomaterials Science
• Immunology
• Materials Chemistry

Background:

• Poly(ethylene glycol) (PEG) hydrogels are promising for implantation due to tunable properties.
• Non-biological materials, including PEG hydrogels, trigger a foreign body response (FBR).
• Incorporating the RGD oligopeptide into PEG hydrogels has shown potential in reducing FBR.

Purpose of the Study:

• To investigate the mechanisms underlying the foreign body response to PEG hydrogels.
• To elucidate the role of the RGD peptide in mediating and reducing FBR.
• To compare the FBR and protein adsorption profiles of PEG, PEG-RGD, and PEG-RDG hydrogels.

Main Methods:

• Subcutaneous implantation of PEG, PEG-RGD, and PEG-RDG hydrogels in mice for 28 days.
• Histological analysis of fibrous capsule formation around implanted hydrogels.
• In vitro and in vivo protein adsorption studies using liquid chromatography-tandem mass spectrometry.

Main Results:

• PEG-RGD hydrogels exhibited a thinner, less dense fibrous capsule compared to PEG and PEG-RDG hydrogels.
• Serum protein adsorption was observed on all PEG-based hydrogels.
• Macrophage adhesion was promoted by adsorbed proteins on PEG and PEG-RDG but not on PEG-RGD hydrogels.
• Proteins associated with wounding and acute inflammation were identified on all hydrogels.

Conclusions:

• The foreign body response to PEG hydrogels may be influenced by adsorbed inflammatory proteins.
• Macrophages can distinguish between different hydrogel chemistries, with RGD improving the FBR.
• RGD modification offers a strategy to mitigate the foreign body response in PEG-based biomaterials.