Matrix metalloproteinase inhibitor within an absorbable coating for vascular applications: Delivery device characterization and the reduction of smooth muscle cell proliferation and migration

Abstract

Significant occurrences of arterial restenosis remain a complicating factor of endovascular stent implantation. The incorporation of GM6001, a matrix metalloproteinase inhibitor (MMPI), into a poly(lactide-co-glycolide) (PLGA) absorbable coating for 316L stainless steel is proposed as a means to reduce the rate of smooth muscle cell proliferation and migration. Coatings were fabricated using a solvent evaporation technique, and the surfaces were characterized by noncontacting profilometry and scanning electron microscopy. Sufficient degradation of the PLGA determined by gel permeation chromatography occurred to release adequate amounts of the GM6001 from the coating within a 7-day period. A cumulative GM6001 release at day 42 was determined to be 77.8 +/- 1.4% of the actual GM6001 content within the coating. The coating containing the GM6001 reduced the rate of in vitro cell growth of human aortic smooth muscle cell (HASMC) by 30.7 and 37.4% compared to the metallic substrate only after 4 and 7 days, respectively. However, the MMP-2 activity normalized to cell number was not statistically different between the GM6001 releasing coating and the metal substrate. Using a scrape wound injury assay, the migration of HASMCs was shown to be decreased by 21.4% with GM6001 released from the PLGA coating compared to metallic substrate only. These results suggest that releasing a MMPI from an absorbable coating of a metallic substrate provides a reduction of HASMC proliferation and migration rates, while preserving the overall MMP activity in efforts to retain normal cellular regulation.