Single-Step Fabrication of Core-Shell Microgels for the Controlled Release of rhBMP-2 and Simvastatin to Induce Osteogenesis

Dual delivery of bioactive molecules (drugs and growth factors) has been attempted to enhance multiple processes during tissue regeneration. For bone tissue engineering, many attempts have been made to enhance osteogenesis coupled angiogenesis, which plays a major role during the bone regeneration process. In this study, core-shell microgels were fabricated for controlled release of recombinant human bone morphogenetic protein 2 (rhBMP-2) and simvastatin from the core and shell, respectively. The microgels were formed with a discrete core and shell structure. The Fourier transform infrared analysis demonstrated the composition of microgel, whereas swelling behavior demonstrated its rapid swelling property. Thermal properties demonstrated the ionic gelation in microgels, which minimizes the thermal degradation of polymers. The degradation study demonstrates that the core-shell structure of microgels was intact until 49 days under physiological conditions. The release profile demonstrates the sequential and controlled release of rhBMP-2 from the core and simvastatin from the shell of the microgels, respectively. The bioactivity of rhBMP-2 and simvastatin released from microgels was preserved as indicated by the alkaline phosphatase (ALP) activity assay. The cell proliferation of mouse preosteoblast (MC3T3-E1) cells and the live-dead staining assay demonstrated cytocompatibility of the microgels. Scanning electron microscopy images demonstrate that the microgels support adhesion of cells on the surface and promote extracellular matrix (ECM) production. The osteogenic differentiation of MC3T3-E1 cells demonstrated the synergistic effect of drugs and growth factors up to 21 days. The controlled and sustained release of simvastatin and rhBMP-2 induced higher mRNA and protein expressions of RUNX2, osteocalcin, and VEGF. The overall results demonstrate the effect of controlled release of rhBMP-2 and simvastatin from core-shell microgels to promote osteogenesis and angiogenesis.

Duke Scholars

Author Hilal Rather