Dual Growth Factor-Modified Microspheres Nesting Human-Derived Umbilical Cord Mesenchymal Stem Cells for Bone Regeneration.

BACKGROUND:Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue.RESULTS:Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis.CONCLUSIONS:The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.