Controlling Molecular Weight of Hyaluronic Acid Conjugated on Amine-rich Surface: Toward Better Multifunctional Biomaterials for Cardiovascular Implants

The molecular weights (MWs) of hyaluronic acid (HA) in extracellular matrix secreted from both vascular endothelial cells (VECs) and vascular smooth muscle, cells (VSMCs) play crucial roles in the cardiovascular physiology, as HA with appropriate MW influences important pathways of cardiovascular homeostasis, inhibits VSMC synthetic phenotype change and proliferation, inhibits platelet activation and aggregation, promotes endothelial monolayer repair and functionalization, and prevents inflammation and atherosclerosis. In this study, HA samples with gradients of MW (4 x 10(3), 1 x 10(5), and 5 x 10(5) Da) were prepared by covalent conjugation to a copolymerized film of polydopamine and hexamethylendiamine (PDA/HD) as multifunctional coatings (PDA/HD-HA) with potential to improve the biocompatibility of cardiovascular biomaterials. The coatings immobilized with high-MW-HA (PDA/HD-HA-2: 1 x 10(5) Da; PDA/HD-HA-3: 5 x 10(5) Da) exhibited a remarkable suppression of platelet activation/aggregation and thrombosis under 15 dyn/cm(2) blood flow and simultaneously suppressed the adhesion and proliferation of VSMC and the adhesion, activation, and inflammatory cytokine release of macrophages. In particular, PDA/HD-HA-2 significantly, enhanced VEC adhesion, proliferation, migration, and functional factors release, as well as the captured number of endothelial progenitor cells under dynamic condition. The in vivo results indicated that the multifunctional surface (PDA/HD-HA-2) created a favorable microenvironment of endothelial monolayer formation and functionalization for promoting reendothelialization and reducing restenosis of cardiovascular biomaterials.