Osteoblastic differentiation and bactericidal activity are enhanced by erythromycin released from PCL/PLGA-PVA coaxial nanofibers

Abstract

Prosthesis with antibiotic-eluting nanofibrous (NF) coating represents coating alternative to prevent periprosthetic joint infection (PJI). In this study, four formulas of erythromycin (EM)-embedded both in core and sheath components of coaxial PCL/PLGA-PVA NF coatings were developed: EM 0 (no EM), EM 100 (100 μg/mL), EM500 (500 μg/mL) and EM1000 (1000 μg/mL). EM doping altered the physicochemical and structural properties of NFs to some extent, including the increase of NF porosity and surface wettability. A sustained EM release from EM-NFs for >4 weeks was observed. Eluents collected from EM-NFs showed strong zone of inhibition (ZOI) to Staphylococcus aureus growth and the sizes of ZOI positively related to the amount of EM released. EM-NFs were nontoxic to rat bone marrow stem cells (rBMSCs). Cell growth was significantly enhanced when comparing rBMSCs cultured on EM-NFs (EM0 and EM 100) to those cultured on NF-free control. Cell differentiation (ALP activity) was notably enhanced by EM100, compared to control and EM0. Eluents from EM-NFs on rBMSCs were also investigated. The presence of 10% EM-NF eluents inhibited the growth of rBMSCs, which was proportional to the amount of EM doped. The ALP activity was notably enhanced by eluents from EM-NFs with the highest activity in EM100 compared to control and EM0. Our data indicate that EM-doped PCL/PLGA-PVA coaxial NF coatings have a great potential to be applied as a new implant coating matrices. Further in vivo testing in animal models is currently planned that should represent the first step in predicting the clinical outcomes of EM-eluting NF coating approach.