A multifunctional dexamethasone-delivery implant fabricated using atmospheric plasma and its effects on apoptosis, osteogenesis and inflammation

Abstract

Implant-based local drug delivery is a unique surgical therapy with many clinical advantages. Atmospheric pressure plasma is a novel non-thermal surface biotechnology that has only recently been applied in enhancing a surgical implant. We are the first to use this technology to successfully create a dexamethasone-delivery metallic implant. Irrespective of the loaded medication, the surface of this novel implant possesses advantageous material features including homogeneity, hydrophilicity, and optimal roughness. UV-vis spectroscopy revealed much more sustainable drug release compared to the implants produced using simple drug attachment. In addition, our drug-releasing implant was found to have multiple biological benefits. As proven by the ELISA data, this multi-layer drug complex provides differential regulation on the cell apoptosis, as well as pro-osteogenic and anti-inflammatory effects on the peri-implant tissue. Furthermore, using the pathway-specific PCR array, our study discovered 28 and 26 upregulated and downregulated genes during osteogenesis and inflammation on our newly fabricated drug-delivery implant, respectively. The medication-induced change in molecular profile serves as a promising clue for designing future implant-based therapy. Collectively, we present atmospheric pressure plasma as a potent tool for creating a surgical implant-based drug-delivery system, which renders multiple therapeutic potentials. Graphical abstract Schematic of the APP-facilitated Dex-delivery implant. This layer-by-layer drug-releasing complex consisted of bottom plasma activation layer, middle medication layer, and top absorbable polymer layer.

Keywords: Apoptosis; Atmospheric plasma; Dexamethasone; Drug delivery; Head and neck surgery; Implant; Inflammation; Macrophage; Osteoblast; Osteogenesis; Otorhinolaryngology.