Improvement of biomedical properties of PEO-treated titanium with flurbiprofen and exosome conjugation

Abstract

Exosome (EXO)-based drug delivery systems have attained a desirable position among scientific researchers and in biomedical applications. In this study, an exosomal coating comprising the anti-inflammatory drug flurbiprofen (FLB) was applied on a commercially pure titanium (cp-Ti) substrate that had undergone surface treatment using plasma electrolytic oxidation (PEO) process. The samples were characterized through field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and water contact angle (WCA) measurement. The results indicated that FLB was loaded onto the EXO and the formation of FLB.EXO was confirmed by FTIR, XRD, AFM and FESEM. Furthermore, FLB.EXO system was treated on PEO-treated substrates and FLB.EXO@PEO system demonstrated a considerable degree of roughness (Ra= 51.16 nm) and exceptional WCA (37.2 ± 0.7 ̊) in comparison to the other samples. The cellular inquiries were assessed through examination of the morphology of bone marrow mesenchymal stem cells (BMMSc) and the MTT assay. The cytotoxicity assessment showed that the FLB.EXO@PEO improved BMMSCs attachment without toxicity. The antibacterial efficacy was determined by means of bacterial adhesion testing against both gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) bacterial strains. FLB.EXO@PEO sample also revealed an excellent antibacterial rate of ∼ 86 % against S. aureus and ∼ 55 % against E. coli. Additionally, in vitro drug release evaluations indicated that sustained drug release was occurred and FLB released from FLB.EXO@PEO during 191 h that was lower than release time in FLB.EXO (120 h). Moreover, the prolonged release was confirmed by constant release rate in both of systems of FLB.EXO and FLB.EXO@PEO after 191 h and 167 h, respectively. The release kinetic of FLB.EXO and FLB.EXO@PEO followed the zero order and first-order model, respectively. Overall, the results indicate that the designed sustained release system have a high potential for development of advanced biomedical implants.