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Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation
Published on: October 29, 2013
Poly(ethylene glycol)-containing hydrogels modulate α-defensin release from polymorphonuclear leukocytes and monocyte
Tyler Jacob Lieberthal1, Hannah Caitlin Cohen2, W John Kao1,2,3
1Department of Biomedical Engineering, University of Wisconsin-Madison, 1550 Engineering Drive, Madison, Wisconsin, 53706.
Abstract:
Polymorphonuclear leukocytes (PMNs) release granule proteins as the first line of defense against bacteria and set up chemotactic gradients that result in monocyte infiltration to the site of injury. Although well established, the role of biomaterials in regulating adherent PMN degranulation and subsequent PMN-monocyte paracrine interactions is less clear. The aim of this study was to determine how biomaterials affect the degranulation of selected biomarkers and downstream monocyte adhesion and transendothelial migration. Poly(ethylene glycol) (PEG)-containing hydrogels (PEG and an interpenetrating network of PEG and gelatin) promote the release of the α-defensins human neutrophil peptides 1-3, but not azurocidin or monocyte chemotactic protein-1. Although human neutrophil peptides 1-3 are monocyte chemoattractants, no subsequent effects on monocyte transmigration are observed in static conditions. Under flow conditions, monocyte adhesion on human umbilical vein endothelial cells stimulated with tumor necrosis factor-α is elevated in the presence of granule proteins from PMNs adherent on polydimethylsiloxane, but not from PMNs cultured on PEG hydrogels. These results suggest that PEG promotes PMN antimicrobial capacity without enhanced monocyte recruitment.
Insights
Poly(ethylene glycol) (PEG) hydrogels enhance antimicrobial peptide release from neutrophils but do not increase subsequent monocyte recruitment. This suggests PEG biomaterials may offer targeted antimicrobial benefits without promoting inflammation.
Area of Science:
- Biomaterials Science
- Immunology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial for innate immunity, releasing granule proteins to combat pathogens and recruit monocytes.
- The influence of biomaterials on PMN degranulation and subsequent inflammatory cell interactions remains incompletely understood.
Purpose of the Study:
- To investigate how different biomaterials, specifically poly(ethylene glycol) (PEG)-containing hydrogels, modulate PMN degranulation.
- To assess the downstream effects of PMN degranulation on monocyte adhesion and transendothelial migration.
Main Methods:
- PMNs were cultured on PEG-hydrogels and polydimethylsiloxane (PDMS).
- Granule protein release (α-defensins, azurocidin, MCP-1) was quantified.
- Monocyte adhesion and transendothelial migration were evaluated under static and flow conditions using human umbilical vein endothelial cells (HUVECs) stimulated with TNF-α.
Main Results:
- PEG hydrogels significantly promoted the release of α-defensins (human neutrophil peptides 1-3) from PMNs.
- No significant increase in monocyte transmigration was observed under static conditions, despite α-defensins being chemoattractants.
- Under flow, monocyte adhesion to TNF-α-stimulated HUVECs was elevated with PMN granule proteins from PDMS, but not from PEG hydrogels.
Conclusions:
- PEG-containing biomaterials enhance the release of antimicrobial peptides from PMNs.
- PEG hydrogels appear to modulate PMN function to promote antimicrobial activity without concurrently increasing monocyte recruitment, suggesting a potential for targeted anti-infective applications.

