Synergistic effect of sustained release of growth factors and dynamic culture on osteoblastic differentiation of mesenchymal stem cells

Microparticles have been utilized as delivery vehicles of soluble factors to modify cellular behavior and therefore enhance tissue engineering regeneration. When incorporated into three-dimensional systems, microparticles can provide geometrical and temporal controlled release of bioactive agents, such as growth factors (GFs) to surrounding cells. This study investigates the effect of GFs release from biopolymer microparticles on osteoblastic differentiation of human mesenchymal stem cells (hMSCs) encapsulated in calcium (Ca)-alginate scaffolds while cultured in a tubular perfusion system bioreactor system. Empirical and deterministic models were used to demonstrate that poly(D,L-lactic-co-glycolic acid)-encapsulated GFs would result in a delayed release profile compared to GFs encapsulated into scaffolds directly. We hypothesized that the dual delivery of human bone-morphogenetic protein 2 (hBMP2) and human vascular endothelial growth factor to cells in dynamic culture would provide molecular and physical cues to promote differentiation. Results indicated that the exposures of hBMP2 and dynamic flow are sufficient in enhancing the osteoblastic differentiation pathway compared to no GF addition and static culture. The GF delivery system in a dynamic flow environment resulted in a synergistic effect on osteoblastic differentiation of hMSCs.