MMP9-sensitive polymers mediate environmentally-responsive bivalirudin release and thrombin inhibition

• Published in: Biomaterials science Vol. 3; no. 1; pp. 41 - 45
• Main Authors: Chu, D S, Sellers, D L, Bocek, M J, Fischedick, A E, Horner, P J, Pun, S H
• Format: Journal Article
• Language: English
• Published: England 01.01.2015
• Subjects: Animals; Biomedical materials; Copolymers; Hirudins - chemical synthesis; Hirudins - chemistry; Hyaluronic Acid - chemistry; Hyaluronic Acid - therapeutic use; Hydrogel, Polyethylene Glycol Dimethacrylate - therapeutic use; Hydrogels; Hydrogels - chemistry; Hydrogels - therapeutic use; Injuries; Matrix Metalloproteinase 9 - chemistry; Matrix Metalloproteinase 9 - metabolism; Methylcellulose - chemistry; Methylcellulose - therapeutic use; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptides; Rats; Recombinant Proteins - chemical synthesis; Recombinant Proteins - chemistry; Scars; Spinal cord; Spinal Cord Injuries - drug therapy; Thrombin; Thrombin - agonists; Thrombin - chemistry
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/c4bm00259h

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.