title: Effect of polyurethane chemistry and protein coating on monocyte differentiation towards a wound healing phenotype macrophage.
abstract: Tissue regeneration alternatives for peripheral vascular disease are actively being investigated; however, few studies in this area have probed the role of the wound healing monocyte-derived macrophage (MDM). Inflammatory MDMs transition to wound healing MDMs as the relative levels of tumor necrosis factor-alpha (TNF-alpha) decrease and IL-10 increase. TNF-alpha has been linked to the regulation of HMGB1 (high mobility group box 1 protein), a nuclear protein that upon macrophage stimulation can be secreted and act as a pro-inflammatory cytokine. This study investigated the influence of a degradable polar hydrophobic ionic polyurethane (D-PHI) on MDM cell expression of pro- versus anti-inflammatory markers, when the material was uncoated or pre-coated with collagen prior to cell studies. Effects were compared to similar groups on tissue culture polystyrene (TCPS). Collagen coated TCPS and D-PHI had significantly more DNA than the uncoated TCPS after 7d (p=0.001 and p=0.006 respectively); however, there was significantly less esterase activity from cells on D-PHI (+/-collagen) than for cells on TCPS after 7d (p=0.002, p=0.0003 respectively). No significant differences in esterase activity were observed between collagen coated and non-coated D-PHI surfaces. Analyses of pro-inflammatory cytokines (TNF-alpha, IL-1beta and HMGB1) secreted from differentiating monocytes adherent to D-PHI demonstrated a decrease whereas anti-inflammatory IL-10 increased over time when compared to TCPS, suggesting that D-PHI was less inflammatory than TCPS. Since D-PHI maintains cell attachment while aiding in the transition of MDM to a wound healing phenotype, this material has qualities suitable to be used in tissue engineering applications where MDM play a key role in tissue regeneration.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5G 1G6, Canada.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: McBane
authors.forename: Loren A
authors.initials: LA
authors.lastname: Matheson
authors.forename: Soroor
authors.initials: S
authors.lastname: Sharifpoor
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Labow
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000502:physiology*; D008297:Male; D008422:Materials Testing; D009000:Monocytes / Q000166:cytology* / Q000502:physiology*; D011140:Polyurethanes / Q000737:chemistry*; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult
chemical_list: D020099:Coated Materials, Biocompatible; D011140:Polyurethanes; D003094:Collagen