Gene Silencing PHD2 to Enhance Tissue Regeneration
Researchers are trying a new approach to speeding regrowth of tissue guided by a scaffold structure:
Studies suggest that increasing angiogenesis - the formation of new blood vessels - may help to heal wounds. One way to enhance the development of blood vessels is through the delivery of growth factors directly to wounds; yet multiple growth factors are needed to produce mature blood vessels, and their concentration as well as the timing of their application must be carefully orchestrated to facilitate proper growth. An alternative approach involves delivering siRNA - short, double-stranded RNA molecules designed to silence a gene of interest - to cells in order to influence genes that induce the formation of new blood vessels.[Researchers used] a novel tissue scaffold that can deliver siRNA to nearby cells over a period of several weeks. Using an siRNA dose 10-100-fold lower than previous studies, the research team efficiently silenced the expression of PHD2 - a protein that normally inhibits blood vessel formation - locally within a biodegradable tissue scaffold. At 33 days post-implant, the scaffolds that delivered PHD2 siRNA had a three-fold increase in the volume of local blood vessels.
To achieve sustained delivery, the researchers first packaged siRNA into nanoparticles, which protect siRNA from being degraded by enzymes found in the extracellular environment. They then combined these nanoparticles with varying amounts of a substance called trehalose. This nanoparticle-trehalose combination was then embedded into a biodegradable tissue scaffold, which they implanted under the skin of a mouse. Trehalose acts as a porogen, meaning it creates pores in the tissue scaffold. As a result, the rate at which nanoparticles are released from the scaffold is directly influenced by the amount of trehalose added. Based on the quantity of trehalose, the system can be tuned to release the nanoparticles to the surrounding cells immediately or over a period of several weeks.