title: Use of monocyte/endothelial cell co-cultures (in vitro) and a subcutaneous implant mouse model (in vivo) to evaluate a degradable polar hydrophobic ionic polyurethane.
abstract: Potential benefits of co-culturing monocytes (MC) with vascular smooth muscle cells have been reported on for tissue engineering applications with a degradable, polar, hydrophobic, and ionic polyurethane (D-PHI). Since the interaction of MC and endothelial cells (EC) within the blood vessel endothelium is also a process of wound repair it was of interest to investigate their function when cultured on the synthetic D-PHI materials, prior to considering the materials' use in vascular engineering. The co-culture (MC/EC) in vitro studies were carried out on films in 96 well plates and porous scaffold disks were prepared for implant studies in an in vivo subcutaneous mouse model. After 7 days in culture, the MC/EC condition was equal to EC growth but had lower esterase activity (a measure of degradative potential), no pro-inflammatory TNF-α and a relatively high anti-inflammatory IL-10 release while the ECs maintained their functional marker CD31. After explantation of the porous scaffolds, a live/dead stain showed that the cells infiltrating the scaffolds were viable and histological stains (May-Grunwald, Trichrome) demonstrated tissue in growth and extracellular matrix synthesis. Lysates from the implant scaffolds analyzed with a cytokine antibody array showed decreased pro-inflammatory cytokines (IL-6, TNF-α, GM-CSF), increased anti-inflammatory cytokines (IL-10, IL-13, TNF-RI), and increased chemotactic cytokines (MCP-1, MCP-5, RANTES). The low foreign body response elicited by D-PHI when implanted in vivo supported the in vitro studies (EC and MC co-culture), demonstrating that D-PHI promoted EC growth along with an anti-inflammatory MC, further demonstrating its potential as a tissue engineering scaffold for vascular applications.
authors.affiliation: University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: McDonald
authors.forename: Loren A
authors.initials: LA
authors.lastname: Matheson
authors.forename: Joanne E
authors.initials: JE
authors.lastname: McBane
authors.forename: Drew
authors.initials: D
authors.lastname: Kuraitis
authors.forename: Erik
authors.initials: E
authors.lastname: Suuronen
authors.forename: Joseph Paul
authors.initials: JP
authors.lastname: Santerre
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Labow
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D015153:Blotting, Western; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D011140:Polyurethanes / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D011140:Polyurethanes