title: Monocyte inflammatory and matrix remodeling response modulated by grafted ECM-derived ligand concentration.
abstract: Ligands presented on biomaterials are a common method to facilitate and control the host response. In a gelatin and polyethylene glycol diacrylate (PEGdA) based semi-interpenetrating network (sIPN), the effects of extracellular matrix (ECM)-derived peptide amount on monocyte adhesion and subsequent protein and mRNA expression were examined. Peptide amount on the sIPN surface was controlled by varying the wt % ratio of the peptide-PEG grafted gelatin to PEGdA. We hypothesized that increasing bioactive peptide amount would modulate human blood-derived monocyte adhesion, cytokine expression, and gene regulation. Monocyte adhesion, release of gelatin degrading proteases matrix metalloprotease-2 (MMP-2), matrix metalloprotease-9 (MMP-9), and proinflammatory protein interleukin-1beta (IL-1beta), and mRNA expression of these proteins were evaluated. We found RGD-PEG grafted sIPNs with higher surface RGD concentrations showed increased adherent density. MMP-2 and IL-1beta protein release was also influenced by the ligand concentration, as initial increase in protein concentration was observed at higher ligand concentrations. MMP-9 protein showed an initial increase that subsided then increased. A decreased IL-1beta protein and mRNA expression was observed over time but MMP-2 mRNA was not detected at any time though MMP-2 protein concentrations showed an initial burst. Hence, monocyte behavior was modulated by surface ligand identity in tandem with ligand concentration.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Wisconsin, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Chung
authors.forename: Heather
authors.initials: H
authors.lastname: Waldeck
authors.forename: David R
authors.initials: DR
authors.lastname: Schmidt
authors.forename: Weiyuan John
authors.initials: WJ
authors.lastname: Kao
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D053583:Interleukin-1beta; D008024:Ligands; D010455:Peptides; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9