Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation

Abstract

Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures. An efficient process for the cell differentiation to obtain a large number of functionalized osteogenic cells is necessary. Therefore, it is strongly recommended to develop strategies to produce sufficient numbers of well-differentiated osteogenic cells from the MSCs. In general, differentiation media with growth factors have been used to facilitate cell differentiation. In the present study, the poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporating the growth factors were included in the media, resulting in releasing growth factors (dexamethasone and beta-glycerophosphate) in the media in the controlled manner. Stable growth and early differentiation of osteogenic cells were achieved by the PLGA-based growth factor releasing system. Moreover, low intensity pulsed ultrasound was applied to this system to induce cell differentiation process. The results revealed that, as a biomarker at early stage of osteogenic cell differentiation, Lamin A/C nuclear protein was efficiently expressed in the cells growing in the presence of PLGA-based growth factor reservoirs and ultrasound. In conclusion, our results showed that the ultrasound stimulation combined with polymeric nanoparticles releasing growth factors could potentially induce osteogenic cell differentiation.