title: Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.
abstract: Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo.
authors.affiliation: School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Love
authors.forename: Kim S
authors.initials: KS
authors.lastname: Jones
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity / Q000187:drug effects; D051117:Scavenger Receptors, Class A / Q000378:metabolism
chemical_list: D016207:Cytokines; D051117:Scavenger Receptors, Class A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D003345:Corticosterone; D006854:Hydrocortisone
keywords: biomaterial; connective tissue; drug delivery; fibrosis; prolyl hydroxylase