In the modern design, most delivery systems for bone regeneration focus on a single growth factor (GF) or a simple mixture of multiple GFs, overlooking the coordination of proliferation and osteogenesis induced by various factors. In this study, core-shell microspheres with poly-l-lactide core-poly(lactic-co-glycolic acid) shell were fabricated, and two GFs, basic fibroblast growth factor 2 (FGF-2) and bone morphogenetic protein 2 (BMP-2) were encapsulated into the core or/and shell. The effects of different release patterns (parallel or sequential manners) of FGF-2 and BMP-2 from these core-shell microspheres on the osteogenic differentiation of low-population density human mesenchymal stem cells (hMSCs) were investigated and the temporal organization of GF release was optimized. In vitro experiments suggested that induction of osteogenic differentiation of low-population density hMSCs by the sequential delivery of FGF-2 followed by BMP-2 from the core-shell microspheres (group S2) was much more efficient than that by the parallel release of the two factors from uniform microspheres (group U). The osteogenic induction by the sequential delivery of BMP-2 followed by FGF-2 from core-shell microspheres (group S1) was even worse than that from microspheres loaded with BMP-2 in both core and shell (group B), although comparable to the cases of parallel delivery of dual GFs (group P). This study showed the advantages of group S2 microspheres in inducing osteogenic differentiation of low-population density hMSCs and the necessity of time sequence studies in tissue engineering while multiple GFs are involved.
Homing of cells to their target organs for tissue defect repair poses a significant challenge to biomaterials scientists and tissue engineers, due to the low efficiency of homing of effective cells to defect sites as well as the difficulties in coordinating cell migration, adhesion, spreading and differentiations. Recent advances in biomaterials have successfully improved the efficiency of homing of mesenchymal stem cells (MSCs) and cell homing-based tissue regeneration. In this review, the process of cell-homing based tissue regeneration was discussed from three different perspectives, including cell surface engineering, scaffold optimization and signaling molecules interactions. Cell surface modification by using polymeric materials offers a simple way to administrate cell migration. Besides, the ordered or anisotropic structures are proved to be more efficient for cell adhesion, spreading and infiltration than relatively random or isotropy structures. Moreover, the coordinated release of different growth factors (GFs), e.g. achieved via core-shell microspheres, can orchestrate the biological processes, including cell growth and differentiations, and significantly enhance the osteogenic differentiation of low population density of MSCs. These developments in biomaterials are not only important for fundamental understanding of materials-cell interactions, but also help understand cell homing-based tissue regeneration from the perspective of materials, which is crucial for the design and fabrication of a new generation of highly functional biomaterials for tissue regeneration.
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