title: In vitro cytotoxicity of injectable and biodegradable poly(propylene fumarate)-based networks: unreacted macromers, cross-linked networks, and degradation products.
abstract: This study evaluates the in vitro biocompatibility of an injectable and biodegradable polymeric network based on poly(propylene fumarate) (PPF) and the cross-linking agent PPF-diacrylate (PPF-DA). Using a methyl tetrazolium (MTT) assay, the effect of the concentrations of PPF and PPF-DA on the cytotoxicity of its unreacted macromers, cross-linked networks, and degradation products was examined. The influence of network structure properties on cell viability and attachment to the cross-linked material was also investigated. The unreacted macromers exhibited a time- and dose-dependent cytotoxic response that increased with more PPF-DA in the mixture. Conversely, the cross-linked networks formed with more PPF-DA did not demonstrate an adverse response because increases in conversion and cross-linking density prevented the extraction of toxic products. Fibroblast attachment was observed on the PPF/PPF-DA networks with the highest double bond conversions. The degradation products, obtained from the complete breakdown of the networks in basic conditions, displayed a dose-dependent cytotoxic response. These results show that there are concerns regarding the biocompatibility of injectable, biodegradable PPF/PPF-DA networks but also sheds light onto potential mechanisms to reduce the cytotoxic effects.
authors.affiliation: Department of Bioengineering, Rice University, MS-142, Houston, Texas 77251-1892, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Timmer
authors.forename: Heungsoo
authors.initials: H
authors.lastname: Shin
authors.forename: R Adam
authors.initials: RA
authors.lastname: Horch
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Ambrose
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D020341:Absorbable Implants; D000179:Acrylates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005347:Fibroblasts; D005650:Fumarates / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D015394:Molecular Structure; D011126:Polypropylenes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats
chemical_list: D000179:Acrylates; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D005650:Fumarates; D011126:Polypropylenes; C097850:poly(propylene fumarate)