Bio-inspired surface modification for biomedical applications

Abstract

A metal stent that could elute plasmid DNA (pDNA) in a controlled manner for substrate-mediated gene transfection was fabricated by first coating with hyaluronic acid (HA) and subsequent deposition of pDNA. To create robust HA coating layer on stainless steel (SS316L) surface, HA was derivatized with dopamine which is a well-known adsorptive molecule involving mussel adhesion process. The HA-coated surface was verified by various analytical techniques and proved to be very hydrophilic and stable, also showing superior biocompatibility in terms of suppressed plasma protein adsorption. For surface loading of pDNA, cationic pDNA/polyethylenimine (PEI) polyplexes were prepared and ionically adsorbed onto the HA-coated SS316L surface. The adsorbed surface exhibited evenly distributed nano-granular topography while the polyplexes maintained the nano-particular morphology. The pDNA was released out in a controlled manner for a period of 10 days with maintaining structural integrity. The dual coated substrate with HA and pDNA/PEI polyplexes exhibited greatly enhanced gene transfection efficiency, when compared to both bare substrate adsorbed with the polyplexes and PEI/pDNA polyelectrolyte multilayers. Dually functionalized stent with HA and pDNA exhibited effective biocompatibility and gene transfection. Drug-eluting stent (DES) has been widely used for the effective treatment of obstructive coronary artery disease, preventing the occurrence of restenosis which was mainly caused by hyper-proliferation of smooth muscle cells. Here, we demonstrate the immobilization of heparin on the metal surface via a bio-inspired manner and subsequent build-up of therapeutic lay-by-layer multilayer assembled from paclitaxel (PTX) encapsulated poly(lactic-co-glycolic acid) grafted hyaluronic acid (HA-g-PLGA) micelles and poly-L-lysine (PLL). It was hypothesized that the heparinized metallic surface would create a non-thrombogenic environment, while controlled release of PTX from the...