Microfluidic Synthesis and Angiogenic Activity of Ginsenoside Rg₁-Loaded PPF Microspheres

Next generation drug-loaded polymer scaffolds for hard tissue engineering require unique structures to enhance release kinetics while enabling bone cell growth (osteogenesis). This study examined the encapsulation of the pro-angiogenic mediator, ginsenoside Rg₁, into biodegradable poly(propylene fumarate) (PPF) microspheres to facilitate osteogenesis, while examining the release mechanism using advanced X-ray absorption near edge structure spectroscopy (XANES). Ginsenoside Rg₁-loaded PPF microspheres were prepared using both an emulsion method and a microfluidic device, with the microfluidic technique providing tunable unimodal PPF spheres ranging in size from 3 to 52 μm by varying the flow rates. The morphology and composition of the Rg₁-loaded PPF microspheres were characterized using FTIR, XRD, and XANES to examine the distribution of ginsenoside Rg₁ throughout the polymer matrix. Encapsulation efficiency and release profiles were studied and quantified by UV-Vis spectrophotometry, showing high encapsulation efficiencies of 95.4 ± 0.8% from the microfluidic approach. Kinetic analysis showed that Rg₁ release from the more monodisperse PPF microspheres was slower with a significantly smaller burst effect than from the polydisperse spheres, with the release following Fickian diffusion. The released Rg₁ maintained its angiogenic effect in vitro, showing that the PPF microspheres are promising to serve as vehicles for long-term controlled drug delivery leading to therapeutic angiogenesis in bone tissue engineering strategies.