title: In vitro cytotoxicity and in vivo biocompatibility of poly(propylene fumarate-co-ethylene glycol) hydrogels.
abstract: The in vitro cytotoxicity and in vivo biocompatibility of poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)] hydrogels were assessed in order to investigate the influence of poly(ethylene glycol) molecular weight and copolymer composition. These materials have application as injectable cardiovascular implants; cytotoxicity due to leachable products, as well as inflammation caused by the biomaterial itself, may ultimately affect the biocompatibility of the implant. We utilized a 7-day in vitro cytotoxicity assay to quantify cell density and cellular proliferation in the presence of copolymer films. The copolymer films exhibited slight to moderate cytotoxicity toward cultured endothelial cells, showing 20-86% viability relative to controls. Cell viability increased with an increasing weight percent of PEG or, to a lesser extent, the molecular weight of PEG. In vivo biocompatibility was assessed using a cage implantation model over a 21-day time period. This system was used to characterize the local cellular and humoral inflammatory response in the surrounding exudate, as well as the size and density of macrophages adherent to the material itself. All copolymer formulations exhibited excellent biocompatibility relative to controls with no significant differences in total leukocyte count among the different formulations. The in vivo inflammatory reaction displayed normal wound healing over 21 days as shown by a progressive decrease in both leukocyte concentration and enzymatic activity. The surface coverage of the copolymer films remained relatively constant from 7 to 21 days. There were no cells larger than 0.003 mm2, which was previously shown to be the threshold value for foreign-body giant cells. These data suggest that P(PF-co-EG) hydrogels have potential for use as injectable biomaterials.
authors.affiliation: Institute of Biosciences and Bioengineering and Department of Chemical Engineering, Rice University, Houston, Texas 77251-1892, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Suggs
authors.forename: M S
authors.initials: MS
authors.lastname: Shive
authors.forename: C A
authors.initials: CA
authors.lastname: Garcia
authors.forename: J M
authors.initials: JM
authors.lastname: Anderson
authors.forename: A G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000633:toxicity*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D005122:Exudates and Transudates / Q000166:cytology / Q000201:enzymology; D005260:Female; D020100:Hydrogels / Q000138:chemical synthesis / Q000633:toxicity*; D020007:Implants, Experimental; D008264:Macrophages / Q000187:drug effects; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010078:Oxazines; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000633:toxicity*; D011126:Polypropylenes / Q000138:chemical synthesis / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013844:Thiazoles; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014966:Xanthenes
chemical_list: D001672:Biocompatible Materials; D004396:Coloring Agents; D020100:Hydrogels; D010078:Oxazines; D011126:Polypropylenes; D013778:Tetrazolium Salts; D013844:Thiazoles; D014966:Xanthenes; C115157:poly(propylene fumarate-co-ethylene glycol); C005843:resazurin; D011092:Polyethylene Glycols; C022616:thiazolyl blue; D013936:Thymidine