Nanohybrid electro-coatings toward therapeutic implants with controlled drug delivery potential for bone regeneration

Abstract

Coatings of metallic implants facilitate a new bioactive interface that favors osteogenic responses and bone formation. Providing a therapeutic capacity to the coatings, involving with a sustainable and controllable delivery of drug molecules, significantly improves the bone regenerative potential. Here we design a novel nanocomposite coating, made of mesoporous silica-shelled hydroxyapatite (MS-HA) nanoparticles and chitosan (Chi), incorporating osteogenic drug dexamethasone phosphate (Dex(P)) within the MS-HA, by the process of an electrophoretic deposition (EPD). MS-HA, produced by a sol-gel reaction of silica onto an HA nanorod, exhibited mono-dispersed core-shell nanoparticles with a size of ∼40 nm and a shell thickness of ∼25 nm. The highly mesoporous structure enabled an effective loading of Dex(P) onto the nanocarriers, showing a loading capacity as high as 15% by weight. The Dex(P) loaded MS-HA were homogenized with Chi in acidic ethanol/water to allow for the EPD process. Nanocomposite coatings were produced well, forming thicknesses a few micrometers largely tunable with EPD parameters and exhibiting MS-HA nanoparticles evenly distributed within Chi matrix. While Dex(P) release from the bare MS-HA nanocarrier was very abrupt, showing a complete release within 24 h, the Dex(P) release from the nanocomposite coatings profiled a highly sustainable pattern over a month. Rat mesenchymal stem cells cultured on the Dex(P)-releasing coatings were substantially stimulated to an osteoblastic lineage, presenting enhanced alkaline phosphate activity and higher levels of osteogenic genes, with respect to coatings free of Dex(P). An indirect culture test also confirmed the long-term release effects of Dex(P) from the coatings over 4 weeks. The currently-developed nanocomposite EPD coatings, with a capacity to load osteogenic drug at large quantity and to deliver for a long-term period, are considered as a promising therapeutic coating platform for metallic bone implants.