title: MMP9-sensitive polymers mediate environmentally-responsive bivalirudin release and thrombin inhibition.
abstract: MMP9-responsive bivalirudin-HPMA copolymers were synthesized for direct, local administration in rat spinal cord contusion injury models. Polymer-conjugated bivalirudin peptides maintained activity while demonstrating enzyme-mediated release upon MMP9 exposure and prolonged release from hyaluronic acid/methylcellulose (HAMC) hydrogels compared to free bivalirudin peptide. Localized administration of bivalirudin copolymers in vivo at the site of rat spinal cord injury decreased cellular proliferation and astrogliosis, suggesting the bivalirudin copolymer and HAMC hydrogel system are a promising therapeutic intervention for reducing immediate inflammatory responses and long term scarring.
authors.affiliation: Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Chu
authors.affiliation: Department of Neurological Surgery and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Sellers
authors.affiliation: Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bocek
authors.affiliation: Department of Neurological Surgery and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Fischedick
authors.affiliation: Department of Neurological Surgery and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Horner
authors.affiliation: Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Pun
mesh_terms: D000818:Animals; D006629:Hirudins / Q000138:chemical synthesis* / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000627:therapeutic use; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry* / Q000378:metabolism; D008747:Methylcellulose / Q000737:chemistry* / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013917:Thrombin / Q000819:agonists* / Q000737:chemistry
chemical_list: D006629:Hirudins; D020100:Hydrogels; D010446:Peptide Fragments; D011994:Recombinant Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D008747:Methylcellulose; D013917:Thrombin; D020780:Matrix Metalloproteinase 9; C074619:bivalirudin