Electrically responsive microreservoires for controllable delivery of dexamethasone in bone tissue engineering

A major concern in orthopedic implants is to decrease the chronic inflammation using specific drug therapies. The newest strategies rely on the controlled delivery of antiinflammatory drugs from carrier biointerfaces designed in the shape of 3D architectures. We report on electrically responsive microreservoires (ERRs) acting as microcontainers for antiinflammatory drugs, as potential biointerfaces in orthopedic implants. The ERRS consist in arrays of vertical microtubes produced by laser direct writing using two photon polymerization effects (2PP_LDW) of a commercially available photoresist, IP-L780. A polypyrrole (conductive)/dexamethasone (drug model) (PPy/Dex) mixture was loaded into the ERRs via a simple immersion process. Then, the ERRs were sealed with a poly(lactic-co-glycolic acid)(PLGA) layer by Matrix Assisted Pulsed Laser Evaporation. ERRs stimulation using voltage cycles between -1 V and +1 V, applied at specific time intervals, at a scan rate of 0.1 Vs(-1), enabled to control the Dex release. The release time scales were between 150 and 275 h, while the concentrations of Dex released were between 450-460 nM after three applied voltage cycles, for different microreservoires dimensions. The proposed approach was validated in osteoblast-like MG-63 cell cultures. Cell viability and adhesion assays showed that the Dex-loaded ERRS sustained the cells growth and preserved their characteristic polygonal shape. Importantly, for the electrically-stimulated Dex release, the level of the alkaline phosphatase activity increased twice, the osteogenic differentiation surpassed by 1.6 times and the relative level of osteocalcin gene expression was 2.2 times higher as compared with the unstimulated drug release. Overall, the ERRs were able to accelerate the cells osteogenic differentiation via electrically controlled release of Dex. (C) 2016 Published by Elsevier B.V.