Project E
Effect of ultrasound on cellular activity
As chondrocytes, the cells that populate the cartilage, have been shown to be responsive to mechanical stimulus, most ex-vivo methods to tissue engineer neo-cartilage have included some mode of mechanical stimulation to enhance and maintain chondrogenesis. While bioreactors based on rotation and compression are well described, and the impact of cyclical and hydrostatic pressure on chondrocyte function are relatively well studied, much remains to be studied about cell growth and proliferation upon ultrasound stimulation (US).Our research has shown that when a continuous ultrasound wave for predetermined time intervals, as opposed to pulsed-ultrasound, was used to stimulate chondrocytes seeded in 3-D scaffolds, cell mitotic and biosynthetic activity could be enhanced [Noriega et al., Tissue Engineering,13(3), 2007]. Furthermore, our recent work has shown US stimulation increases gene and protein expression of chondrocyte-specific markers, namely, agggrecan and collagen-II but does not impact MMP-3, a key matrix degrading enzyme (see figure-1).
Additionally, my recent work has shown that stimulation via US impacts the gene expression of integrins; the cellular hooks that, tether a cell to the extracellular matrix and play a role in signal transduction; a process by which a cell transforms one kind of signal or stimulus into another and thus allowing cells to make rapid and flexible responses [Hasanova et al.,2007]. I anticipate investigating these research venues by developing a novel US-aided bioreactor configuration that incorporates a feed-back control to provide different regimes of mechanical conditioning to engineered tissues at different stages of development.
Figure 1: RT-PCR analysis. PCR amplification was performed using primers specific to the sequences of interest genes and GAPH gene as loading control. C:control; 1X to 8X:indicate frequency of US stimulation per day at 5.0 MHz for 51 secs.
In the broad area of tissue engineering, and as it applies to the generation of tissue engineered neo-cartilage, I am particularly interested in the following two research areas: (1) enhancement of biomaterial functionality and (2) designing cell instructive environments.