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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.

SUBMITTER: Chu DS

PROVIDER: S-EPMC4289632 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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

Chu D S DS Sellers D L DL Bocek M J MJ Fischedick A E AE Horner P J PJ Pun S H SH

Biomaterials science 20150101 1

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 prolifera ...[more]

PMID: 25589953

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